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    P200010S010C

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    of 149

    Technical Information

    Guardant Health, Inc.


    ͷͲͷ‡‘„• ‘–”Ǥ
    ‡†™‘‘†‹–›ǡͻͶͲ͸͵

    1. Intended Use
    —ƒ”†ƒ–͵͸Ͳ̺š‹•ƒ“—ƒŽ‹–ƒ–‹˜‡‡š–‰‡‡”ƒ–‹‘•‡“—‡ ‹‰Ǧ„ƒ•‡†in vitro†‹ƒ‰‘•–‹ †‡˜‹ ‡–Šƒ–
    —•‡•–ƒ”‰‡–‡†Š‹‰Š–Š”‘—‰Š’—–Š›„”‹†‹œƒ–‹‘Ǧ„ƒ•‡† ƒ’–—”‡–‡ Š‘Ž‘‰›ˆ‘”†‡–‡ –‹‘‘ˆ•‹‰Ž‡
    — Ž‡‘–‹†‡˜ƒ”‹ƒ–•ȋ•Ȍǡ‹•‡”–‹‘•ƒ††‡Ž‡–‹‘•ȋ‹†‡Ž•Ȍ‹ͷͷ‰‡‡•ǡ ‘’›—„‡”ƒ’Ž‹ˆ‹ ƒ–‹‘•
    • Ȍ‹–™‘ȋʹȌ‰‡‡•ǡƒ†ˆ—•‹‘•‹ˆ‘—”ȋͶȌ‰‡‡•Ǥ —ƒ”†ƒ–͵͸Ͳš—–‹Ž‹œ‡• ‹” —Žƒ–‹‰ ‡ŽŽǦˆ”‡‡
    ȋ ˆȌˆ”‘’Žƒ•ƒ‘ˆ’‡”‹’Š‡”ƒŽ™Š‘Ž‡„Ž‘‘† ‘ŽŽ‡ –‡†‹–”‡ ‡ŽŽǦ ”‡‡Ž‘‘†
    ‘ŽŽ‡ –‹‘—„‡•ȋ•ȌǤŠ‡–‡•–‹•‹–‡†‡†–‘„‡—•‡†ƒ•ƒ ‘’ƒ‹‘†‹ƒ‰‘•–‹ –‘‹†‡–‹ˆ›’ƒ–‹‡–•
    ™Š‘ƒ›„‡‡ˆ‹–ˆ”‘–”‡ƒ–‡–™‹–Š–Š‡–Š‡”ƒ’‹‡•Ž‹•–‡†‹Table 1 ‹ƒ ‘”†ƒ ‡™‹–Š–Š‡ƒ’’”‘˜‡†
    –Š‡”ƒ’‡—–‹ ’”‘†— –Žƒ„‡Ž‹‰Ǥ

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy
    ‘Ǧ•ƒŽŽ ‡ŽŽŽ—‰ ƒ ‡” EGFR‡š‘ͳͻ†‡Ž‡–‹‘•ǡͺͷͺǡƒ†͹ͻͲȗ   ̺ȋ‘•‹‡”–‹‹„Ȍ
    ȋȌ EGFR‡š‘ʹͲ‹•‡”–‹‘• ̺ȋƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™Ȍ
    ERBB2ȀHER2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†  ̺ȋˆƒǦ–”ƒ•–—œ—ƒ„
    ‡š‘ʹͲ‹•‡”–‹‘•Ȍ †‡”—š–‡ ƒǦš‹Ȍ
    KRAS ͳʹ ̻ȋ•‘–‘”ƒ•‹„Ȍ 
    ”‡ƒ•– ƒ ‡” ESR1‹••‡•‡—–ƒ–‹‘•„‡–™‡‡ ‘†‘• ̻ȋ‡Žƒ ‡•–”ƒ–Ȍ
    ͵ͳͲǦͷͶ͹

    ‡‰ƒ–‹˜‡”‡•—Ž–ˆ”‘ƒ’Žƒ•ƒ•’‡ ‹‡†‘‡•‘–ƒ••—”‡–Šƒ––Š‡’ƒ–‹‡–ǯ•–—‘”‹•‡‰ƒ–‹˜‡ˆ‘”
    ‰‡‘‹ ˆ‹†‹‰•Ǥƒ–‹‡–•™Š‘ƒ”‡‡‰ƒ–‹˜‡ˆ‘”–Š‡„‹‘ƒ”‡”•Ž‹•–‡†‹Table 1•Š‘—Ž†„‡”‡ˆŽ‡š‡†–‘
    –‹••—‡„‹‘’•›–‡•–‹‰ˆ‘”Table 1„‹‘ƒ”‡”•—•‹‰ƒ Ǧƒ’’”‘˜‡†–—‘”–‹••—‡–‡•–ǡ‹ˆˆ‡ƒ•‹„Ž‡Ǥ
    ȗŠ‡‡ˆˆ‹ ƒ ›‘ˆ  ȋ‘•‹‡”–‹‹„ȌŠƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹–Š‡EGFR͹ͻͲ’Žƒ•ƒǦ
    ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡‘”—‘™’‘’—Žƒ–‹‘ƒ† Ž‹‹ ƒŽ†ƒ–ƒˆ‘”͹ͻͲ’Žƒ•ƒǦ’‘•‹–‹˜‡’ƒ–‹‡–•
    ƒ”‡Ž‹‹–‡†Ǣ–Š‡”‡ˆ‘”‡ǡ–‡•–‹‰—•‹‰’Žƒ•ƒ•’‡ ‹‡•‹•‘•–ƒ’’”‘’”‹ƒ–‡ˆ‘” ‘•‹†‡”ƒ–‹‘‹
    ’ƒ–‹‡–•ˆ”‘™Š‘ƒ–—‘”„‹‘’•› ƒ‘–„‡‘„–ƒ‹‡†Ǥ
    ††‹–‹‘ƒŽŽ›ǡ–Š‡–‡•–‹•‹–‡†‡†–‘’”‘˜‹†‡–—‘”—–ƒ–‹‘’”‘ˆ‹Ž‹‰–‘„‡—•‡†„›“—ƒŽ‹ˆ‹‡†Š‡ƒŽ–Š
    ƒ”‡’”‘ˆ‡••‹‘ƒŽ•‹ƒ ‘”†ƒ ‡™‹–Š’”‘ˆ‡••‹‘ƒŽ‰—‹†‡Ž‹‡•‹‘ ‘Ž‘‰›ˆ‘” ƒ ‡”’ƒ–‹‡–•™‹–Šƒ›
    •‘Ž‹†ƒŽ‹‰ƒ–‡‘’Žƒ•ǤŠ‡–‡•–‹•ˆ‘”—•‡™‹–Š’ƒ–‹‡–•’”‡˜‹‘—•Ž›†‹ƒ‰‘•‡†™‹–Š ƒ ‡”ƒ†‹
    ‘Œ— –‹‘™‹–Š‘–Š‡”Žƒ„‘”ƒ–‘”›ƒ† Ž‹‹ ƒŽˆ‹†‹‰•Ǥ
    ‡‘‹ ˆ‹†‹‰•‘–Š‡”–Šƒ–Š‘•‡Ž‹•–‡†‹Table 1ƒ”‡‘–’”‡• ”‹’–‹˜‡‘” ‘ Ž—•‹˜‡ˆ‘”Žƒ„‡Ž‡†—•‡
    ‘ˆƒ›•’‡ ‹ˆ‹ –Š‡”ƒ’‡—–‹ ’”‘†— –Ǥ
    —ƒ”†ƒ–͵͸Ͳš‹•ƒ•‹‰Ž‡Ǧ•‹–‡ƒ••ƒ›’‡”ˆ‘”‡†ƒ– —ƒ”†ƒ– ‡ƒŽ–Šǡ  Ǥ

    ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    2. Contraindications
    Š‡”‡ƒ”‡‘‘™ ‘–”ƒ‹†‹ ƒ–‹‘•Ǥ

    3. Warnings and Precautions


    ƒǤ Ž–‡”ƒ–‹‘•”‡’‘”–‡†ƒ›‹ Ž—†‡•‘ƒ–‹ ȋ‘–‹Š‡”‹–‡†Ȍ‘”‰‡”Ž‹‡ȋ‹Š‡”‹–‡†ȌƒŽ–‡”ƒ–‹‘•ǤŠ‡
    ƒ••ƒ›ˆ‹Ž–‡”•‰‡”Ž‹‡˜ƒ”‹ƒ–•ˆ”‘”‡’‘”–‹‰‡š ‡’–ˆ‘”’ƒ–Š‘‰‡‹ BRCA1ǡBRCA2ǡATMǡƒ†
    CDK12ƒŽ–‡”ƒ–‹‘•Ǥ ‘™‡˜‡”ǡ‹ˆƒ”‡’‘”–‡†ƒŽ–‡”ƒ–‹‘‹••—•’‡ –‡†–‘„‡‰‡”Ž‹‡ǡ ‘ˆ‹”ƒ–‘”›
    –‡•–‹‰•Š‘—Ž†„‡ ‘•‹†‡”‡†‹–Š‡ƒ’’”‘’”‹ƒ–‡ Ž‹‹ ƒŽ ‘–‡š–Ǥ
    „Ǥ Š‡–‡•–‹•‘–‹–‡†‡†–‘”‡’Žƒ ‡‰‡”Ž‹‡–‡•–‹‰‘”–‘’”‘˜‹†‡‹ˆ‘”ƒ–‹‘ƒ„‘—– ƒ ‡”
    ’”‡†‹•’‘•‹–‹‘Ǥ
    Ǥ ‘ƒ–‹ ƒŽ–‡”ƒ–‹‘•‹ATMƒ†CDK12ƒ”‡‘–”‡’‘”–‡†„›–Š‡–‡•–ƒ•–Š‡›ƒ”‡‡š Ž—†‡†ˆ”‘–Š‡
    –‡•–̵•”‡’‘”–ƒ„Ž‡”ƒ‰‡Ǥ
    †Ǥ ‡‘‹ ˆ‹†‹‰•ˆ”‘ ˆƒ›‘”‹‰‹ƒ–‡ˆ”‘ ‹” —Žƒ–‹‰–—‘”ȋ –Ȍˆ”ƒ‰‡–•ǡ
    ‰‡”Ž‹‡ƒŽ–‡”ƒ–‹‘•ǡ‘”‘Ǧ–—‘”•‘ƒ–‹ ƒŽ–‡”ƒ–‹‘•ǡ•— Šƒ• Ž‘ƒŽŠ‡ƒ–‘’‘‹‡•‹•‘ˆ
    ‹†‡–‡”‹ƒ–‡’‘–‡–‹ƒŽȋ ȌǤ
    ‡Ǥ ŽŽ‘™–Š‡–—„‡–‘ˆ‹ŽŽ ‘’Ž‡–‡Ž›—–‹Ž„Ž‘‘†•–‘’•ˆŽ‘™‹‰‹–‘–Š‡–—„‡Ǥ†‡”ˆ‹ŽŽ‹‰‘ˆ–—„‡•™‹–Š
    Ž‡••–Šƒͷ‘ˆ„Ž‘‘†ȋ„‘––‘‘ˆ–Š‡Žƒ„‡Ž‹†‹ ƒ–‡•ͷˆ‹ŽŽ™Š‡–—„‡‹•Š‡Ž†˜‡”–‹ ƒŽŽ›Ȍƒ›
    Ž‡ƒ†–‘‹ ‘””‡ –ƒƒŽ›–‹ ƒŽ”‡•—Ž–•‘”’‘‘”’”‘†— –’‡”ˆ‘”ƒ ‡ǤŠ‹•–—„‡Šƒ•„‡‡†‡•‹‰‡†–‘
    ˆ‹ŽŽ™‹–ŠͳͲ‘ˆ„Ž‘‘†Ǥ

    4. Limitations
    ƒǤ ‘” in vitro†‹ƒ‰‘•–‹ —•‡Ǥ
    „Ǥ ‘”’”‡• ”‹’–‹‘—•‡‘Ž›ǤŠ‹•–‡•–—•–„‡‘”†‡”‡†„›ƒ“—ƒŽ‹ˆ‹‡†‡†‹ ƒŽ’”‘ˆ‡••‹‘ƒŽ‹
    ƒ ‘”†ƒ ‡™‹–Š Ž‹‹ ƒŽŽƒ„‘”ƒ–‘”›”‡‰—Žƒ–‹‘•Ǥ
    Ǥ Š‡‡ˆˆ‹ ƒ ›‘ˆ  ȋ‘•‹‡”–‹‹„ȌŠƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹–Š‡EGFR͹ͻͲ’Žƒ•ƒǦ
    ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡‘”—‘™’‘’—Žƒ–‹‘ƒ† Ž‹‹ ƒŽ†ƒ–ƒˆ‘”͹ͻͲ’Žƒ•ƒǦ’‘•‹–‹˜‡
    ’ƒ–‹‡–•ƒ”‡Ž‹‹–‡†Ǣ–Š‡”‡ˆ‘”‡ǡ–‡•–‹‰—•‹‰’Žƒ•ƒ•’‡ ‹‡•‹•‘•–ƒ’’”‘’”‹ƒ–‡ˆ‘”
    ‘•‹†‡”ƒ–‹‘‹’ƒ–‹‡–•ˆ”‘™Š‘ƒ–—‘”„‹‘’•› ƒ‘–„‡‘„–ƒ‹‡†Ǥ
    †Ǥ   ‡ˆˆ‹ ƒ ›Šƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹’ƒ–‹‡–•™‹–ŠEGFR‡š‘ͳͻ†‡Ž‡–‹‘•δͲǤͲͺΨ ǡ
    ‹’ƒ–‹‡–•™‹–ŠEGFRͺͷͺδͲǤͲͻΨ ǡƒ†‹’ƒ–‹‡–•™‹–ŠEGFR͹ͻͲδͲǤͲ͵Ψ Ǥ
    ‡Ǥ ‡ˆˆ‹ ƒ ›Šƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹’ƒ–‹‡–•™‹–ŠEGFR‡š‘ʹͲ‹•‡”–‹‘•δͲǤͲʹΨ
     Ǥ
    ˆǤ ‡ˆˆ‹ ƒ ›Šƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹’ƒ–‹‡–•™‹–ŠKRAS ͳʹ„‹‘ƒ”‡”•δͲǤͳͳΨ
     Ǥ
    ‰Ǥ  ‡ˆˆ‹ ƒ ›Šƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹’ƒ–‹‡–•™‹–ŠERBB2‡š‘ʹͲ‹•‡”–‹‘•δͲǤͲ͵Ψ
     ƒ†‹’ƒ–‹‡–•™‹–ŠERBB2•δͲǤʹ͵Ψ Ǥ
    ŠǤ ‡ˆˆ‹ ƒ ›Šƒ•‘–„‡‡‡•–ƒ„Ž‹•Š‡†‹’ƒ–‹‡–•™‹–ŠESR1‹••‡•‡—–ƒ–‹‘•δͲǤͲ͵ΨǤ
    ‹Ǥ Š‡–‡•–‹•‘–‹–‡†‡†–‘„‡—•‡†ˆ‘”•–ƒ†ƒŽ‘‡†‹ƒ‰‘•–‹ ’—”’‘•‡•Ǥ
    ŒǤ Š‡–‡•–‹•‹–‡†‡†–‘„‡’‡”ˆ‘”‡†‘•’‡ ‹ˆ‹ •‡”‹ƒŽ—„‡”Ǧ ‘–”‘ŽŽ‡†‹•–”—‡–•„›
    —ƒ”†ƒ– ‡ƒŽ–Šǡ  Ǥ
    Ǥ ‡‰ƒ–‹˜‡”‡•—Ž–ˆ‘”ƒ›‰‹˜‡˜ƒ”‹ƒ–†‘‡•‘–’”‡ Ž—†‡–Š‡’”‡•‡ ‡‘ˆ–Š‹•˜ƒ”‹ƒ–‹–—‘”
    –‹••—‡Ǥ

    ʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ŽǤ ‡ ‹•‹‘•‘’ƒ–‹‡– ƒ”‡ƒ†–”‡ƒ–‡–—•–„‡„ƒ•‡†‘–Š‡‹†‡’‡†‡–‡†‹ ƒŽŒ—†‰‡–‘ˆ
    –Š‡–”‡ƒ–‹‰’Š›•‹ ‹ƒǡ–ƒ‹‰‹–‘ ‘•‹†‡”ƒ–‹‘ƒŽŽƒ’’Ž‹ ƒ„Ž‡‹ˆ‘”ƒ–‹‘ ‘ ‡”‹‰–Š‡
    ’ƒ–‹‡–̵• ‘†‹–‹‘ǡ•— Šƒ•’ƒ–‹‡–ƒ†ˆƒ‹Ž›Š‹•–‘”›ǡ’Š›•‹ ƒŽ‡šƒ‹ƒ–‹‘•ǡ‹ˆ‘”ƒ–‹‘ˆ”‘
    ‘–Š‡”†‹ƒ‰‘•–‹ –‡•–•ǡƒ†’ƒ–‹‡–’”‡ˆ‡”‡ ‡•ǡ‹ƒ ‘”†ƒ ‡™‹–Š–Š‡•–ƒ†ƒ”†‘ˆ ƒ”‡Ǥ
    Ǥ –•Š‡††‹‰”ƒ–‡ƒ›„‡Ž‘™‡”‹’ƒ–‹‡–•™‹–Š’”‹ƒ”› ‡–”ƒŽ‡”˜‘—••›•–‡ȋȌ–—‘”•Ǥ

    5. Guardant360 CDx Overview


    ͷǤͳǤ ‡•–—ƒ”›ƒ†š’Žƒƒ–‹‘
    —ƒ”†ƒ–͵͸Ͳš‹•ƒ‡š–‰‡‡”ƒ–‹‘•‡“—‡ ‹‰Ǧ„ƒ•‡†–‡•–ˆ‘”–Š‡†‡–‡ –‹‘‘ˆ‰‡‡–‹ ƒŽ–‡”ƒ–‹‘•‹
    ͷͷ‰‡‡•ˆ”‡“—‡–Ž›—–ƒ–‡†‹ ƒ ‡”Ǥ –‹•ƒ ‘’ƒ‹‘†‹ƒ‰‘•–‹ –‘‹†‡–‹ˆ›’ƒ–‹‡–•™Š‘ƒ›
    „‡‡ˆ‹–ˆ”‘–”‡ƒ–‡–™‹–Š–Š‡–ƒ”‰‡–‡†–Š‡”ƒ’›Ž‹•–‡†‹Table 1‘ˆ–Š‡ –‡†‡†•‡Ǥ††‹–‹‘ƒŽŽ›ǡ
    –Š‡–‡•–‹•‹–‡†‡†–‘’”‘˜‹†‡–—‘”—–ƒ–‹‘’”‘ˆ‹Ž‹‰–‘„‡—•‡†„›“—ƒŽ‹ˆ‹‡†Š‡ƒŽ–Š ƒ”‡
    ’”‘ˆ‡••‹‘ƒŽ•‹ƒ ‘”†ƒ ‡™‹–Š’”‘ˆ‡••‹‘ƒŽ‰—‹†‡Ž‹‡•‹‘ ‘Ž‘‰›ˆ‘” ƒ ‡”’ƒ–‹‡–•™‹–Šƒ›
    •‘Ž‹†ƒŽ‹‰ƒ–‡‘’Žƒ•Ǥ
    Š‡–‡•–”‡’‘”–‹ Ž—†‡•˜ƒ”‹ƒ–•”‡’‘”–‡†‹–Š‡ˆ‘ŽŽ‘™‹‰ ƒ–‡‰‘”‹‡•ȋ Table 2ȌǤ

    Table 2. Category Definitions


    Guardant360 CDx
    Prescriptive
    use for a
    Therapeutic Clinical Analytical
    Category Product Performance Performance Comments
    ƒ–‡‰‘”›ͳǣ ‡• ‡• ‡• –„‹‘ƒ”‡”•Ž‹‡†–‘–Š‡•ƒˆ‡
    ‘’ƒ‹‘ ƒ†‡ˆˆ‡ –‹˜‡—•‡‘ˆ–Š‡ ‘””‡•’‘†‹‰
    ‹ƒ‰‘•–‹ ȋšȌ –Š‡”ƒ’‡—–‹ ’”‘†— –ǡˆ‘”™Š‹ Š
    —ƒ”†ƒ–͵͸ͲšŠƒ•†‡‘•–”ƒ–‡†
    Ž‹‹ ƒŽ’‡”ˆ‘”ƒ ‡•Š‘™–‘
    •—’’‘”––Š‡”ƒ’‡—–‹ ‡ˆˆ‹ ƒ ›ƒ†
    •–”‘‰ƒƒŽ›–‹ ƒŽ’‡”ˆ‘”ƒ ‡ˆ‘”–Š‡
    „‹‘ƒ”‡”Ǥ
    ƒ–‡‰‘”›ʹǣ ‘ ‘ ‡• –„‹‘ƒ”‡”•™‹–Š•–”‘‰
    –‹‘ƒ”‡”• ‡˜‹†‡ ‡‘ˆ Ž‹‹ ƒŽ•‹‰‹ˆ‹ ƒ ‡
    ™‹–Š–”‘‰ ’”‡•‡–‡†„›‘–Š‡” Ǧƒ’’”‘˜‡†
    ˜‹†‡ ‡‘ˆŽ‹‹ ƒŽ Ž‹“—‹†„‹‘’•› ‘’ƒ‹‘†‹ƒ‰‘•–‹ •
    ‹‰‹ˆ‹ ƒ ‡‹ ˆ‘”™Š‹ Š —ƒ”†ƒ–͵͸ͲšŠƒ•
    – †‡‘•–”ƒ–‡†ƒƒŽ›–‹ ƒŽ”‡Ž‹ƒ„‹Ž‹–›„—–
    ‘– Ž‹‹ ƒŽ’‡”ˆ‘”ƒ ‡Ǥ
    ƒ–‡‰‘”›͵ǣ ‘ ‘ ‡• –„‹‘ƒ”‡”•™‹–Š‡˜‹†‡ ‡‘ˆ
    ‹‘ƒ”‡”•™‹–Š Ž‹‹ ƒŽ•‹‰‹ˆ‹ ƒ ‡’”‡•‡–‡†„›
    ˜‹†‡ ‡‘ˆŽ‹‹ ƒŽ –‹••—‡Ǧ„ƒ•‡† Ǧƒ’’”‘˜‡†
    ‹‰‹ˆ‹ ƒ ‡‹–‹••—‡ ‘’ƒ‹‘†‹ƒ‰‘•–‹ •‘”
    •—’’‘”–‡†„›ǣ•–”‘‰ ’”‘ˆ‡••‹‘ƒŽ‰—‹†‡Ž‹‡•ˆ‘”™Š‹ Š
    ƒƒŽ›–‹ ƒŽ˜ƒŽ‹†ƒ–‹‘ —ƒ”†ƒ–͵͸ͲšŠƒ•†‡‘•–”ƒ–‡†
    —•‹‰ – ƒƒŽ›–‹ ƒŽ’‡”ˆ‘”ƒ ‡‹ Ž—†‹‰
    ƒƒŽ›–‹ ƒŽƒ —”ƒ ›ǡƒ† ‘ ‘”†ƒ ‡
    ‘ˆ„Ž‘‘†Ǧ„ƒ•‡†–‡•–‹‰–‘–‹••—‡Ǧ„ƒ•‡†
    –‡•–‹‰ˆ‘”–Š‡„‹‘ƒ”‡”Ǥ

    ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Guardant360 CDx
    Prescriptive
    use for a
    Therapeutic Clinical Analytical
    Category Product Performance Performance Comments
    ƒ–‡‰‘”›͵ǣ ‘ ‘ ‡• –„‹‘ƒ”‡”•™‹–Š‡˜‹†‡ ‡‘ˆ
    ‹‘ƒ”‡”•™‹–Š Ž‹‹ ƒŽ•‹‰‹ˆ‹ ƒ ‡’”‡•‡–‡†„›
    ˜‹†‡ ‡‘ˆŽ‹‹ ƒŽ –‹••—‡Ǧ„ƒ•‡† Ǧƒ’’”‘˜‡†
    ‹‰‹ˆ‹ ƒ ‡‹–‹••—‡ ‘’ƒ‹‘†‹ƒ‰‘•–‹ •‘”
    •—’’‘”–‡†„›ǣ ’”‘ˆ‡••‹‘ƒŽ‰—‹†‡Ž‹‡•ˆ‘”™Š‹ Š
    ƒƒŽ›–‹ ƒŽ˜ƒŽ‹†ƒ–‹‘ —ƒ”†ƒ–͵͸ͲšŠƒ•†‡‘•–”ƒ–‡†
    —•‹‰ – ‹‹—ƒƒŽ›–‹ ƒŽ’‡”ˆ‘”ƒ ‡
    ‹ Ž—†‹‰ƒƒŽ›–‹ ƒŽƒ —”ƒ ›Ǥ
    ƒ–‡‰‘”›Ͷǣ ‘ ‘ ‡• –„‹‘ƒ”‡”•™‹–Š‡‡”‰‡–
    –Š‡”‹‘ƒ”‡”• ‡˜‹†‡ ‡„ƒ•‡†‘’‡‡”Ǧ”‡˜‹‡™‡†
    ™‹–Š‘–‡–‹ƒŽ ’—„Ž‹ ƒ–‹‘•ˆ‘”‰‡‡•Ȁ˜ƒ”‹ƒ–•‹
    Ž‹‹ ƒŽ‹‰‹ˆ‹ ƒ ‡ –‹••—‡ǡ˜ƒ”‹ƒ–‹ˆ‘”ƒ–‹‘ˆ”‘™‡ŽŽǦ
    —”ƒ–‡†’—„Ž‹ †ƒ–ƒ„ƒ•‡•ǡ‘”‹Ǧ˜‹–”‘
    ’”‡Ǧ Ž‹‹ ƒŽ‘†‡Ž•ǡˆ‘”™Š‹ Š
    —ƒ”†ƒ–͵͸ͲšŠƒ•†‡‘•–”ƒ–‡†
    ‹‹—ƒƒŽ›–‹ ƒŽ’‡”ˆ‘”ƒ ‡Ǥ

    ͷǤʹǤ ƒ’Ž‡‘ŽŽ‡ –‹‘ƒ†‡•–”†‡”‹‰


    ‘‘”†‡” —ƒ”†ƒ–͵͸Ͳšǡ–Š‡‡•–‡“—‹•‹–‹‘ ‘”ȋ Ȍ’”‘˜‹†‡†™‹–Š–Š‡ —ƒ”†ƒ–͵͸Ͳš
    Ž‘‘†‘ŽŽ‡ –‹‘‹–—•–„‡ˆ—ŽŽ› ‘’Ž‡–‡†ƒ†•‹‰‡†„›–Š‡‘”†‡”‹‰’Š›•‹ ‹ƒ‘”‘–Š‡”ƒ—–Š‘”‹œ‡†
    ‡†‹ ƒŽ’”‘ˆ‡••‹‘ƒŽǤ‡ˆ‡”–‘–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‘‘†‘ŽŽ‡ –‹‘‹– •–”— –‹‘•ˆ‘”•‡ˆ‘”
    ˆ—”–Š‡”†‡–ƒ‹Ž•ƒ„‘—– ‘ŽŽ‡ –‹‰„Ž‘‘†•ƒ’Ž‡•ƒ†•Š‹’’‹‰•ƒ’Ž‡•–‘–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽ
    ƒ„‘”ƒ–‘”›Ǥ
    ‘‘”†‡”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‘‘†‘ŽŽ‡ –‹‘‹–‘”‘„–ƒ‹ƒ‡Ž‡ –”‘‹ ˜‡”•‹‘‘ˆ–Š‡ ǡ ‘–ƒ –
    –Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‡–‡”˜‹ ‡•†‡’ƒ”–‡–ȋ‡ŽǣͺͷͷǤ͸ͻͺǤͺͺͺ͹ǡ ƒšǣͺͺͺǤͻ͹ͶǤͶʹͷͺǡ‘”ƒ‹Žǣ
    Ž‹‡–•‡”˜‹ ‡•̷‰—ƒ”†ƒ–Š‡ƒŽ–ŠǤ ‘ȌǤ

    ͷǤ͵Ǥ ”‹ ‹’Ž‡•‘ˆ–Š‡”‘ ‡†—”‡


    —ƒ”†ƒ–͵͸Ͳš‹•’‡”ˆ‘”‡†„›ƒ•‹‰Ž‡Žƒ„‘”ƒ–‘”›ǡ–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽƒ„‘”ƒ–‘”›ǡ
    Ž‘ ƒ–‡†‹‡†™‘‘†‹–›ǡǡǤ —ƒ”†ƒ–͵͸Ͳš‹• ‘’‘•‡†‘ˆ–Š‡ˆ‘ŽŽ‘™‹‰ƒŒ‘”’”‘ ‡••‡•ǣ
    x Š‘Ž‡Ž‘‘†‘ŽŽ‡ –‹‘ƒ†Š‹’’‹‰
    x Žƒ•ƒ •‘Žƒ–‹‘ƒ† ˆš–”ƒ –‹‘
    x ‹„”ƒ”›”‡’ƒ”ƒ–‹‘ƒ†”‹ Š‡–
    x ‡“—‡ ‹‰
    x ƒ–ƒƒŽ›•‹•ƒ†‡’‘”–‹‰
    Š‡ —ƒ”†ƒ–͵͸ͲšŽ‘‘†‘ŽŽ‡ –‹‘‹–‹•—•‡†„›–Š‡‘”†‡”‹‰Žƒ„‘”ƒ–‘”‹‡•Ȁ’Š›•‹ ‹ƒ•–‘ ‘ŽŽ‡ –
    ™Š‘Ž‡„Ž‘‘†•’‡ ‹‡•ƒ†•Š‹’–Š‡–‘–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽƒ„‘”ƒ–‘”›ǤŠ‘Ž‡„Ž‘‘†‹•
    ‘ŽŽ‡ –‡†‹–Š‡’”‘˜‹†‡†„Ž‘‘† ‘ŽŽ‡ –‹‘–—„‡•ǡ–”‡ ‡ŽŽǦ ”‡‡•ǡ™Š‹ Š•–ƒ„‹Ž‹œ‡ ˆ
    ƒ†— Ž‡ƒ–‡†„Ž‘‘† ‡ŽŽ•ˆ‘”•Š‹’’‹‰Ǥ
    ŽŽ‘–Š‡””‡ƒ‰‡–•ǡƒ–‡”‹ƒŽ•ƒ†‡“—‹’‡–‡‡†‡†–‘’‡”ˆ‘”–Š‡ƒ••ƒ›ƒ”‡—•‡†‡š Ž—•‹˜‡Ž›‹–Š‡
    —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽƒ„‘”ƒ–‘”›Ǥ
    Š‘Ž‡„Ž‘‘†•’‡ ‹‡•ƒ”‡’”‘ ‡••‡†‹–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽƒ„‘”ƒ–‘”›™‹–Š‹͹†ƒ›•‘ˆ
    „Ž‘‘† ‘ŽŽ‡ –‹‘Ǥ‹‹—‘ˆͷ™Š‘Ž‡„Ž‘‘†—•–„‡”‡ ‡‹˜‡†‹‘”†‡”–‘ƒ Š‹‡˜‡‘’–‹ƒŽ
    ’‡”ˆ‘”ƒ ‡ˆ‘”–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ••ƒ›Ǥ†‡”ˆ‹ŽŽ‹‰‘ˆ–—„‡•™‹–ŠŽ‡••–Šƒͷ‘ˆ„Ž‘‘†ƒ›
    Ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Ž‡ƒ†–‘‹ ‘””‡ –ƒƒŽ›–‹ ƒŽ”‡•—Ž–•‘”’‘‘”’”‘†— –’‡”ˆ‘”ƒ ‡ǤŽƒ•ƒ‹•‹•‘Žƒ–‡†˜‹ƒ ‡–”‹ˆ—‰ƒ–‹‘
    ƒ† ˆ‹•‡š–”ƒ –‡†ˆ”‘’Žƒ•ƒǤ ˆǡͷ–‘͵Ͳ‰ǡ‹•–Š‡—•‡†–‘’”‡’ƒ”‡•‡“—‡ ‹‰Ž‹„”ƒ”‹‡•
    ™Š‹ Šƒ”‡‡”‹ Š‡†„›Š›„”‹†‹œƒ–‹‘ ƒ’–—”‡ǤŠ‡‡”‹ Š‡†Ž‹„”ƒ”‹‡•ƒ”‡–Š‡•‡“—‡ ‡†—•‹‰‡š–
    ‰‡‡”ƒ–‹‘•‡“—‡ ‹‰‘–Š‡ ŽŽ—‹ƒ‡š–‡“ͷͷͲ’Žƒ–ˆ‘”Ǥ
    ‡“—‡ ‹‰†ƒ–ƒƒ”‡–Š‡ƒƒŽ›œ‡†—•‹‰ƒ —•–‘Ǧ†‡˜‡Ž‘’‡†„‹‘‹ˆ‘”ƒ–‹ •’‹’‡Ž‹‡†‡•‹‰‡†–‘
    †‡–‡ –•ǡ‹†‡Ž•ǡ•ƒ†ˆ—•‹‘•ˆ”‘ ˆǤ‡•—Ž–•ȋ†‡–‡ –‡†‘”‘–†‡–‡ –‡†Ȍƒ”‡’”‡•‡–‡†‹
    ƒ”‡•—Ž–•”‡’‘”–Ǥ‘–†‡–‡ –‡†”‡•—Ž–ˆ”‘ƒ’Žƒ•ƒ•’‡ ‹‡ˆ‘”ƒ›‰‹˜‡˜ƒ”‹ƒ–†‘‡•‘–’”‡ Ž—†‡
    –Š‡’”‡•‡ ‡‘ˆ–Š‹•˜ƒ”‹ƒ–‹–—‘”–‹••—‡Ǥ
    Š‡†‡˜‹ ‡‹•†‡•‹‰‡†–‘†‡–‡ –’”‡Ǧ†‡ˆ‹‡†ƒ††‡‘˜‘˜ƒ”‹ƒ–•‹–Š‡‰‡‡•‘—–Ž‹‡†‹Table 3Ǥ
    ‡–ƒ‹Ž•‘ƒŽŽ˜ƒ”‹ƒ–•”‡’‘”–‡† ƒ„‡ˆ‘—†‹Section 8 Additional Guardant360 CDx Variant
    DetailsǤ

    Table 3. Genes Containing Alterations Reported by Guardant360 CDx


    Alteration Type Genes
    ‹‰Ž‡— Ž‡‘–‹†‡ AKT1ǡALKǡAPCǡARǡARAFǡATMȗǡBRAFǡBRCA1ȗȗǡBRCA2ȗȗǡCCND1ǡCDH1ǡCDK4ǡCDK6ǡ
    ƒ”‹ƒ–•ȋ•Ȍ CDK12ȗǡCDKN2AǡCTNNB1ǡEGFRǡERBB2ǡESR1ǡFGFR1ǡFGFR2ǡFGFR3ǡGATA3ǡGNA11ǡ
    GNAQǡHRASǡIDH1ǡIDH2ǡKITǡKRASǡMAP2K1ǡMAP2K2ǡMETǡMLH1ǡMTORǡMYCǡNF1ǡ
    NFE2L2ǡNRASǡNTRK1ǡNTRK3ǡPDGFRAǡPIK3CAǡPTENǡRAF1ǡRETǡRHEBǡROS1ǡSMAD4ǡ
    SMOǡSTK11ǡTERTǡTSC1ǡVHL
    †‡Ž• AKT1ǡALKǡAPCǡATMȗǡBRAFǡBRCA1ȗȗǡBRCA2ȗȗǡCDH1ǡCDK12ȗǡCDKN2AǡEGFRǡERBB2ǡ
    ESR1ǡFGFR2ǡGATA3ǡHNF1AǡHRASǡKITǡKRASǡMETǡMLH1ǡNF1ǡPDGFRAǡPIK3CAǡPTENǡ
    RETǡROS1ǡSTK11ǡTSC1ǡVHL
    ‘’›—„‡” ERBB2ǡMET
    ’Ž‹ˆ‹ ƒ–‹‘•ȋ•Ȍ
    —•‹‘• ALKǡNTRK1ǡRETǡROS1
    ȗ‡’‘”–‹‰‹•‡ƒ„Ž‡†ˆ‘”’ƒ–Š‘‰‡‹ ‰‡”Ž‹‡ƒŽ–‡”ƒ–‹‘•‘Ž›Ǥ‘ƒ–‹ ƒŽ–‡”ƒ–‹‘•™‹ŽŽ‘–„‡”‡’‘”–‡†Ǥ
    ȗȗ‡’‘”–‹‰‹•‡ƒ„Ž‡†ˆ‘”„‘–Š‰‡”Ž‹‡ƒ†•‘ƒ–‹ ƒŽ–‡”ƒ–‹‘•Ǥ

    ͷǤͶǤ ‡ƒ‰‡–ǡƒ–‡”‹ƒŽǡƒ†“—‹’‡–•ƒ‰‡
    ‡ƒ‰‡–•ǡƒ–‡”‹ƒŽ•ǡƒ†‡“—‹’‡–‡‡†‡†–‘’‡”ˆ‘”–Š‡–‡•–ƒ”‡—•‡†‡š Ž—•‹˜‡Ž›‹–Š‡ —ƒ”†ƒ–
    ‡ƒŽ–ŠŽ‹‹ ƒŽƒ„‘”ƒ–‘”›Ǥ —ƒ”†ƒ–͵͸Ͳš‹•‹–‡†‡†–‘„‡’‡”ˆ‘”‡†™‹–Š–Š‡ˆ‘ŽŽ‘™‹‰
    ‹•–”—‡–•ǡ–‘„‡‹†‡–‹ˆ‹‡†„›•’‡ ‹ˆ‹ •‡”‹ƒŽ—„‡”•ǡƒ•‡‡†‡†Ǥ
    x ‰‹Ž‡–‡ Š‘Ž‘‰‹‡•ͶʹͲͲƒ’‡–ƒ–‹‘ •–”—‡–
    x ’’Ž‹‡†‹‘•›•–‡•‡”‹–‹ͻ͸Ǧ‡ŽŽŠ‡”ƒŽ› Ž‡”
    x ƒ‹Ž–‘‘’ƒ›‹ ”‘Žƒ„
    x ƒ‹Ž–‘‘’ƒ›‹ ”‘Žƒ„Ž‡–
    x ŽŽ—‹ƒ‡š–‡“ͷͷͲ‡“—‡ ‹‰›•–‡
    x ‹ƒ‰‡ •›’Š‘› •–”—‡–

    6. Summary of Performance Characteristics


    ‡”ˆ‘”ƒ ‡ Šƒ”ƒ –‡”‹•–‹ •™‡”‡‡•–ƒ„Ž‹•Š‡†—•‹‰ Ž‹‹ ƒŽ•ƒ’Ž‡•ˆ”‘’ƒ–‹‡–•™‹–Šƒ™‹†‡”ƒ‰‡
    ‘ˆ ƒ ‡”–›’‡•ǡ‹ Ž—†‹‰–Š‘•‡™‹–ŠǤŠ‡ Ž‹‹ ƒŽ•ƒ’Ž‡• ‘•‹•–‡†‘ˆ’‘‘Ž•‘ˆ ˆˆ”‘
    Ž‹‹ ƒŽ•ƒ’Ž‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”–›’‡•ǡ’‘‘Ž•‘ˆ ˆˆ”‘ Ž‹‹ ƒŽ•ƒ’Ž‡•†‡”‹˜‡†ˆ”‘‘‡
    ƒ ‡”–›’‡ȋe.g.ǡ•ƒ’Ž‡•ˆ”‘’ƒ–‹‡–•™‹–ŠȌ‘”—Ǧ’‘‘Ž‡† Ž‹‹ ƒŽ•ƒ’Ž‡•Ǥ–—†‹‡•‹ Ž—†‡
    š˜ƒ”‹ƒ–•ƒ•™‡ŽŽƒ•ƒ„”‘ƒ†”ƒ‰‡‘ˆ”‡’”‡•‡–ƒ–‹˜‡ƒŽ–‡”ƒ–‹‘–›’‡•ȋ•ǡ‹†‡Ž•ǡ•ǡƒ†
    ˆ—•‹‘•Ȍ‹˜ƒ”‹‘—•‰‡‘‹  ‘–‡š–•ƒ ”‘••ƒ—„‡”‘ˆ‰‡‡•Ǥ—‡–‘Ž‹‹–ƒ–‹‘•‹ Ž‹‹ ƒŽ•ƒ’Ž‡
    ƒ˜ƒ‹Žƒ„‹Ž‹–›ƒ††—‡–‘–Š‡”ƒ”‹–›‘ˆ–Š‡ˆ—•‹‘•”‡’‘”–‡†„›–Š‡ —ƒ”†ƒ–͵͸Ͳšǡ ‘–”‹˜‡†•ƒ’Ž‡•
    ™‡”‡—–‹Ž‹œ‡†ˆ‘”•‘‡‘Ǧ Ž‹‹ ƒŽ•–—†‹‡•Ǥ ‘–”‹˜‡†•ƒ’Ž‡ˆ— –‹‘ƒŽ Šƒ”ƒ –‡”‹œƒ–‹‘•–—†›™ƒ•
    ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‘†— –‡†–‘†‡‘•–”ƒ–‡ ‘’ƒ”ƒ„Ž‡’‡”ˆ‘”ƒ ‡‘ˆ ‘–”‹˜‡†•ƒ’Ž‡•ƒ†‡‘ˆ ‡ŽŽŽ‹‡ ˆƒ†
    Ž‹‹ ƒŽ•ƒ’Ž‡ ˆ•‘–Šƒ–ˆ—•‹‘ ‡ŽŽŽ‹‡ ˆƒ–‡”‹ƒŽ ‘—Ž†„‡—•‡†‹•‘‡‘Ǧ Ž‹‹ ƒŽ
    •–—†‹‡•Ǥ —•‹‘’‘•‹–‹˜‡ Ž‹‹ ƒŽ•ƒ’Ž‡•™‡”‡—•‡†–‘ ‘ˆ‹”–Š‡‡•–‹ƒ–‡†Ž‹‹–‘ˆ†‡–‡ –‹‘ǡ
    ƒƒŽ›–‹ ƒŽƒ —”ƒ ›ƒ†’”‡ ‹•‹‘Ǥ

    ͸ǤͳǤ ƒŽ›–‹ ƒŽ —”ƒ ›Ȁ‘ ‘”†ƒ ‡

    a. Concordance - Comparison to NGS Comparator Method #1


    Š‡†‡–‡ –‹‘‘ˆƒŽ–‡”ƒ–‹‘•„› —ƒ”†ƒ–͵͸Ͳš™ƒ• ‘’ƒ”‡†–‘”‡•—Ž–•‘ˆƒ‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡†
     ƒ••ƒ›Ǥƒ’Ž‡•ˆ”‘Ͷ͵ͻ†‘‘”•™‹–Š†‹ˆˆ‡”‡– ƒ ‡”–›’‡•™‡”‡ ‘ŽŽ‡ –‡†ˆ‘”–Š‡•–—†›Ǥ‹š–‡‡
    ͳ͸Ȍ •ƒ’Ž‡•ˆƒ‹Ž‡†–‡•–‹‰™‹–Š–Š‡ ‘’ƒ”ƒ–‘”ƒ••ƒ›†—‡–‘‹•–”—‡–ˆƒ‹Ž—”‡•ǡ™Š‹Ž‡‡Ž‡˜‡ȋͳͳȌ
    •ƒ’Ž‡•ˆƒ‹Ž‡†–‡•–‹‰™‹–Š–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ••ƒ›†—‡–‘ƒ‹•–”—‡–ˆƒ‹Ž—”‡†—‡–‘ƒ’‘™‡”
    ‘—–ƒ‰‡ǤͶͳʹ•ƒ’Ž‡•”‡ƒ‹‡† ‘’”‹•‹‰–Š”‡‡ ‘ŽŽ‡ –‹‘•‡–•ƒ•ˆ‘ŽŽ‘™•Ǥ
    ‘ŽŽ‡ –‹‘•‡–‘‡ ‘•‹•–‡†‘ˆͳͲͲ†‘‘”•ƒ’Ž‡••‡Ž‡ –‡†™‹–Š–Š‡ ‘’ƒ”ƒ–‘”ƒ••ƒ› ‘•‡ —–‹˜‡Ž›
    ™‹–Š‘—–•‡Ž‡ –‹‘ˆ‘”ƒ›•’‡ ‹ˆ‹ ˜ƒ”‹ƒ–•Ǥ‹ ‡–Š‡ˆ‹”•–•ƒ’Ž‡ ‘ŽŽ‡ –‹‘™ƒ•‡š’‡ –‡†–‘Žƒ ƒ›
    ”ƒ”‡˜ƒ”‹ƒ–•ǡ‹–Š‡•‡ ‘† ‘ŽŽ‡ –‹‘•‡–ǡƒ•‡–‘ˆͳͲͲ’‘•‹–‹˜‡•ƒ’Ž‡•™‡”‡•‡Ž‡ –‡†™‹–Š–Š‡
    ‘’ƒ”ƒ–‘”ƒ••ƒ›Ǥ‘ŽŽ‡ –‹‘•‡––Š”‡‡ ‘•‹•–‡†‘ˆͳͷͻ•ƒ’Ž‡••‡Ž‡ –‡†ˆ”‘–Š‡ —ƒ”†ƒ– ‡ƒŽ–Š
    „‹‘„ƒ„ƒ•‡†‘ —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•–‘‹ Ž—†‡ƒ††‹–‹‘ƒŽ”ƒ”‡˜ƒ”‹ƒ–•‹ Ž—†‹‰‰‡‡ˆ—•‹‘•
    ™Š‹ Š™‡”‡‘–ƒ˜ƒ‹Žƒ„Ž‡ˆ”‘ ‘ŽŽ‡ –‹‘•‡–•ͳƒ†ʹǤ‘ŽŽ‡ –‹‘•‡–ˆ‘—” ‘•‹•–‡†‘ˆͷ͵•ƒ’Ž‡•ˆ”‘
    –Š‡ —ƒ”†ƒ– ‡ƒŽ–Š„‹‘„ƒ„ƒ•‡†‘ —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•–‘‹ Ž—†‡ƒ††‹–‹‘ƒŽƒ–‡‰‘”›͵
    ˜ƒ”‹ƒ–•Ǥ
    ˆͶͳʹ’ƒ–‹‡–•ǡ–™‘•ƒ’Ž‡•ˆƒ‹Ž‡†‘ —ƒ”†ƒ–͵͸Ͳšǡƒ†–Š”‡‡•ƒ’Ž‡•ˆƒ‹Ž‡†™‹–Š–Š‡
    ‘’ƒ”ƒ–‘” ƒ••ƒ›Ǥ –‘–ƒŽǡͶͲ͹†‘‘”•ƒ’Ž‡•ƒ ”‘••ͳͺ ƒ ‡”–›’‡•ǡ™Š‹ ŠƒŽŽ’ƒ••‡†‡˜‡”›
    ‡–”‹ ™‡”‡—•‡†ˆ‘”–Š‡ ‘ ‘”†ƒ ‡ƒƒŽ›•‹•ǤŠ‡ ƒ ‡”–›’‡•”‡’”‡•‡–‡†‹–Š‹••–—†›‹ Ž—†‡†
    Ž—‰ȋͳͺͺȌǡ‰ƒ•–”‘‹–‡•–‹ƒŽȋͺʹȌǡ ‘Ž‘ȋʹͶȌǡ„”‡ƒ•–ȋͶͺȌǡŠ‡ƒ†ƒ†‡ ȋͳ͵Ȍǡ’”‘•–ƒ–‡ȋͳʹȌǡ
    ‰‡‹–‘—”‹ƒ”›ȋ͹Ȍǡ„Žƒ††‡”ȋ͵Ȍǡ•–‘ƒ Šȋ͵Ȍǡ’ƒ ”‡ƒ•ȋ͵Ȍǡ‡†‘ ”‹‡ȋʹȌǡŽ‹˜‡”ȋʹȌǡ‘˜ƒ”‹ƒȋʹȌǡ‹†‡›
    ȋʹȌǡ‰›‡ ‘Ž‘‰‹ ȋͳȌǡ‡•‘’Šƒ‰—•ȋͳȌǡ•‹ ͺ Ȍǡƒ†‘–Š‡”ȋ͸ȌǤ•—ƒ”›‘ˆ‘•‹–‹˜‡‡” ‡–‰”‡‡‡–
    ȋȌƒ†‡‰ƒ–‹˜‡‡” ‡–‰”‡‡‡–ȋȌ™‹–ŠͻͷΨ ‘ˆ‹†‡ ‡‹–‡”˜ƒŽ•ȋ Ȍ‹•’”‘˜‹†‡†‹
    Table 4ˆ‘”šƒŽ–‡”ƒ–‹‘•‹•ƒ’Ž‡•ˆ”‘–Š‡‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǡi.e.ǡͳͺͺ’ƒ–‹‡–•™‹–Š
    Ǥ‰”‡‡‡–”ƒ–‡•ˆ‘”‡ƒ Š‘ˆ–Š‡š˜ƒ”‹ƒ–•”ƒ‰‡†ˆ”‘ͻͷΨ–‘ͳͲͲΨˆ‘”ǡƒ†ˆ”‘
    ͻͺǤͳΨ–‘ͻͻǤͻΨˆ‘”ǤŠ‡”‡’‘”–‡†ƒ†™‡”‡‘–ƒ†Œ—•–‡†ˆ‘”–Š‡†‹•–”‹„—–‹‘‘ˆ•ƒ’Ž‡•
    ˆ”‘ ‘ŽŽ‡ –‹‘•‡–•͵ƒ†Ͷ•‡Ž‡ –‡†—•‹‰ —ƒ”†ƒ–”‡•—Ž–•Ǥ•—ƒ”›‘ˆƒ†ˆ‘”
    ‘–Š‡” Ž‹‹ ƒŽŽ›•‹‰‹ˆ‹ ƒ–˜ƒ”‹ƒ– ƒ–‡‰‘”‹‡•ƒ†ˆ‘”’ƒ‡Ž™‹†‡ˆ‘”•ƒ†‹†‡Ž•‘˜‡”ƒŽŽ•ƒ’Ž‡
    ‘ŽŽ‡ –‹‘•‹•’”‘˜‹†‡†‹Table 4Ǥ
    ‘•‹–‹˜‡ƒ‰”‡‡‡–”ƒ–‡•™‡”‡‡˜ƒŽ—ƒ„Ž‡ˆ‘”‡‹‰Š–‡‡ȋͳͺȌ’ƒ–‹‡–•™‹–Š Ž‹‹ ƒŽƒ–‡‰‘”›ʹ˜ƒ”‹ƒ–•ǡ
    ™Š‹ Š ‘•‹•–‡†‘ˆ Ž‹‹ ƒŽŽ›”‡Ž‡˜ƒ–PIK3CA—–ƒ–‹‘•‹„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•–Šƒ–‹ Ž—†‡†ͷͶͷǡ
    ͷͶʹǡͷͶͷǡ ͳͲͶ͹ǡƒ† ͳͲͶ͹˜ƒ”‹ƒ–•Ǥ‘ ‘”†ƒ ‡ƒƒŽ›•‹•”‡•—Ž–‡†‹ͻͷǤͲΨƒ†
    ͳͲͲΨˆ‘”–Š‡ƒ–‡‰‘”›ʹ˜ƒ”‹ƒ–•Ǥ
    ‘•‹–‹˜‡ƒ‰”‡‡‡–”ƒ–‡•ˆ‘” Ž‹‹ ƒŽƒ–‡‰‘”‹‡•͵ƒ†Ͷ˜ƒ”‹ƒ–•”‡•—Ž–‡†‹ͻʹǤͺΨƒ†͹͹Ǥ͹Ψ
    ǡ”‡•’‡ –‹˜‡Ž›Ǥƒ”‹ƒ–•‹ Ž‹‹ ƒŽ ƒ–‡‰‘”›͵ƒ†Ͷ•Š‘™‡†ͻͻǤͺΨƒ†ͻͻǤͻΨǤ
    METƒ’Ž‹ˆ‹ ƒ–‹‘•Šƒ†ƒ‘ˆͷ͹Ǥ͹Ψǡ™Š‹ Š‹•ƒ––”‹„—–‡†–‘†‹ˆˆ‡”‡ ‡•‹”‡’‘”–‹‰‘ˆ ‘’›
    —„‡”ƒŽ–‡”ƒ–‹‘•„›–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡ ‘’ƒ”ƒ–‘”ƒ••ƒ›ǤŠ‡ —ƒ”†ƒ–͵͸Ͳš”‡’‘”–•
    ‘‘Ž›ˆ‘ ƒŽƒ’Ž‹ˆ‹ ƒ–‹‘•ƒ†‘– Š”‘‘•‘‡Ǧƒ”ƒ’Ž‹ˆ‹ ƒ–‹‘•ǡ™Š‹Ž‡–Š‡  ‘’ƒ”ƒ–‘”
    ƒ••ƒ›”‡’‘”–•ƒŽŽƒ’Ž‹ˆ‹ ƒ–‹‘•Ǥ

    ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Š‡•–—†›†‡‘•–”ƒ–‡†ƒ‘ˆ͹͵ǤʹΨˆ‘”‹†‡Ž•ǡͺ͹ǤʹΨˆ‘”•ƒ†εͻͻΨˆ‘”–Š‡‡–‹”‡
    ”‡’‘”–ƒ„Ž‡”ƒ‰‡ǡi.e.ǡ’ƒ‡ŽǦ™‹†‡ǡ†‡‘•–”ƒ–‹‰–Š‡ƒƒŽ›–‹ ƒŽƒ —”ƒ ›‘ˆ–Š‡†‡˜‹ ‡Ǥ

    Table 4. Summary of Concordance between Guardant360 CDx and NGS Comparator Method #1
    Guardant3 Guardant3 Guardant3 Guardant3
    60 CDx(+), 60 CDx(+), 60 CDx(-), 60 CDx(-), Possible PPA NPA
    Alteration Comparat Comparat Comparat Comparat Variants Patients (95% (95%
    Type or #1 (+) or #1 (-) or #1 (+) or #1 (-) (n) (n) CI) CI)
    EGFR͹ͻͲ ͳͻ ͵ ͳ ͳͷ͵ ͳ ͳ͹͸ ͻͷǤͲΨ ͻͺǤͳΨ
    ȋ͹ͷǤͳΨǡ ȋͻͶǤͷΨǡ
    ͻͻǤͻΨȌ ͻͻǤ͸ΨȌ
    EGFRͺͷͺ ͳͺ ͳ Ͳ ͳͷ͹ ͳ ͳ͹͸ ͳͲͲǤͲΨ ͻͻǤͶΨ
    ȋͺͳǤͷΨǡ ȋͻ͸ǤͷΨǡ
    ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    EGFR‡š‘ͳͻ ͵Ͳ ͳ ͳ ͳͲʹͶ ͸ ͳ͹͸ ͻ͸ǤͺΨ ͻͻǤͻΨ
    †‡Ž‡–‹‘• ȋͺ͵Ǥ͵Ψǡ ȋͻͻǤͷΨǡ
    ͻͻǤͻΨȌ ͻͻǤͻΨȌ
    ƒ–‡‰‘”›ʹ ͳͻ Ͳ ͳ ʹʹͲ ͷ Ͷͺ ͻͷǤͲΨ ͳͲͲǤͲΨ
    ƒ”‹ƒ–• ȋ͹ͷǤͳΨǡ ȋͻͺǤ͵
    ͻͻǤͻΨȌ Ψǡ
     ͳͲͲǤͲΨȌ
    ƒ–‡‰‘”›͵ ʹͲ͹ ʹʹ ͳ͸ ͳͲʹʹͲ ͺ͸ Ȁȗ ͻʹǤͺΨ ͻͻǤͺΨ
    ƒ”‹ƒ–•  ȋͺͺǤ͸Ψǡ ȋͻͻǤ͹Ψǡ
    ͻͷǤͺΨȌ ͻͻǤͻΨȌ
     
    ƒ–‡‰‘”›Ͷ ͶͲͶ ͻʹ ͳͳ͸ ͳͷͷʹ͸ͻ ͵ͺ͵ ͶͲ͹ ͹͹Ǥ͹Ψ ͻͻǤͻΨ
    ƒ”‹ƒ–•  ȋ͹͵ǤͻΨǡ ȋͻͻǤͻΨǡ
    ͺͳǤʹΨȌ ͳͲͲǤͲΨȌ
    MET• ͳͷ ͵ ͳͳ ͵͹ͺ ͳ ͶͲ͹ ͷ͹Ǥ͹Ψ ͻͻǤʹΨ
    ȋ͵͸ǤͻΨǡ ȋͻ͹Ǥ͹Ψǡ
    ͹͸Ǥ͹ΨȌ ͻͻǤͺΨȌ
     
    ERBB2• ʹ͸ ͳ ʹ ͵͹ͺ ͳ ͶͲ͹ ͻʹǤͻΨ ͻͻǤ͹Ψ
    ȋ͹͸ǤͷΨǡ ȋͻͺǤͷΨǡ
    ͻͻǤͳΨȌ ͳͲͲǤͲΨȌ
     
    NTRK1 —•‹‘• ͸ Ͳ Ͳ ͶͲͳ ͳ ͶͲ͹ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    ȋͷͶǤͲΨǡ ȋͻͻǤͳΨǡ
    ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    RET —•‹‘• ͳͶ ͵ ͳ ͵ͺͻ ͳ ͶͲ͹ ͻ͵Ǥ͵Ψ ͻͻǤʹΨ
    ȋ͸ͺǤͳΨǡ ȋͻ͹ǤͺΨǡ
    ͻͻǤͺΨȌ ͻͻǤͺΨȌ
     
    ALK —•‹‘• ͳͲ ʹ Ͳ ͵ͻͷ ͳ ͶͲ͹ ͳͲͲǤͲΨ ͻͻǤͷΨ
    ȋ͸ͻǤʹΨǡ ȋͻͺǤʹΨǡ
    ͳͲͲǤͲΨȌ ͻͻǤͻΨȌ
    ROS1 —•‹‘• ͳͳ Ͳ Ͳ ͵ͻ͸ ͳ ͶͲ͹ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    ȋ͹ͳǤͷΨǡ ȋͻͻǤͳΨǡ
    ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ

    ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Guardant3 Guardant3 Guardant3 Guardant3
    60 CDx(+), 60 CDx(+), 60 CDx(-), 60 CDx(-), Possible PPA NPA
    Alteration Comparat Comparat Comparat Comparat Variants Patients (95% (95%
    Type or #1 (+) or #1 (-) or #1 (+) or #1 (-) (n) (n) CI) CI)
    ƒ‡ŽǦ‹†‡ Ͷͻ͹ ͹͸ ͹͵ ͳʹͷͳͳ͹ ͵Ͳͻ ͶͲ͹ ͺ͹ǤʹΨ ͻͻǤͻΨ
    • ȋͺͶǤʹΨǡ ȋͻͻǤͻΨǡ
    ͺͻǤͺΨȌ ͳͲͲǤͲΨȌ
    ƒ‡ŽǦ‹†‡ ͳ͵ͳ ͵ͷ Ͷͺ ͸ͶͲͻʹ ͳͷͺ ͶͲ͹ ͹͵ǤʹΨ ͳͲͲǤͲΨ
    †‡Ž• ȋ͸͸ǤͳΨǡ ȋͻͻǤͻΨǡ
    ͹ͻǤͷΨȌ ͳͲͲǤͲΨȌ
    ȗ ‘”ƒ–‡‰‘”›͵ǡ‘—„‡”‹•‰‹˜‡ǤŠ‹•‹•„‡ ƒ—•‡ƒ–‡‰‘”›͵‹•ƒ‡”‰‡‘ˆƒ›†‹ˆˆ‡”‡–˜ƒ”‹ƒ–•ǡ‡ƒ Š™‹–Šƒ•’‡ ‹ˆ‹ 
    •‡–‘ˆ ƒ ‡”–›’‡•–Šƒ–“—ƒŽ‹ˆ›–Š‡˜ƒ”‹ƒ––‘„‡Ž‘‰‹ƒ–‡‰‘”›͵ǤŠ‹•‡ƒ•–Šƒ–ƒ†‹ˆˆ‡”‡–—„‡”‘ˆ’ƒ–‹‡–•™ƒ•
    ƒ••‘ ‹ƒ–‡†™‹–Š‡ƒ Š˜ƒ”‹ƒ–™‹–Š‹ƒ–‡‰‘”›͵Ǥ ‘”–Š‹•Ž‡˜‡Žǡ–Š‡ ‘ ‘”†ƒ–Ž›‡‰ƒ–‹˜‡’‘’—Žƒ–‹‘™ƒ• ‘’—–‡†ƒ•–Š‡
    •—‘ˆ–Š‡ ‘ ‘”†ƒ–Ž›‡‰ƒ–‹˜‡’‘’—Žƒ–‹‘•‹ˆ‡ƒ Š˜ƒ”‹ƒ–‹–Š‹• ƒ–‡‰‘”›™ƒ•–”‡ƒ–‡†‹†‡’‡†‡–Ž›Ǥ

    b. Concordance – Comparison to NGS Comparator Method #2


    Š‡†‡–‡ –‹‘‘ˆEGFR‡š‘ʹͲ‹•‡”–‹‘•ƒ†ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ
    ‹•‡”–‹‘•Ȍ„› —ƒ”†ƒ–͵͸Ͳš™ƒ• ‘’ƒ”‡†–‘”‡•—Ž–•‘ˆƒ‘–Š‡”‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡†’Žƒ•ƒǦ
    „ƒ•‡† ƒ••ƒ›Ǥ
    •ƒ’Ž‡•ˆ”‘ʹ͹͹’ƒ–‹‡–•™‡”‡ ‘ŽŽ‡ –‡†ˆ‘”–Š‡•–—†›‘EGFR‡š‘ʹͲ‹•‡”–‹‘•‹ Ž—†‹‰
    •ƒ’Ž‡•ˆ”‘ƒŽŽ•—„Œ‡ –•–‡•–‡†‹–Š‡ƒ••‘ ‹ƒ–‡† Ž‹‹ ƒŽ•–—†›™‹–Š•—ˆˆ‹ ‹‡–”‡ƒ–ƒ–‡”‹ƒŽˆ‘”
    –‡•–‹‰™‹–Š–Š‡ ‘’ƒ”ƒ–‘”‡–Š‘†Ǥ ‘—”•ƒ’Ž‡•ˆƒ‹Ž‡†–‡•–‹‰™‹–Š–Š‡ ‘’ƒ”ƒ–‘”ƒ••ƒ›†—‡–‘
    •‡“—‡ ‹‰ˆƒ‹Ž—”‡•ǡ™Š‹Ž‡‘‡•ƒ’Ž‡ˆƒ‹Ž‡†–‡•–‹‰™‹–Š —ƒ”†ƒ–͵͸Ͳš†—‡–‘‡”‹ Š‡–ˆƒ‹Ž—”‡Ǥ
    ƒ†ƒ”‡”‡’‘”–‡†‹Table 5„‡Ž‘™Ǥˆ‘–‡ǡ–Š‡ ‘’ƒ”ƒ–‘”‡–Š‘†—•‡†™ƒ•Ž‡•••‡•‹–‹˜‡
    –Šƒ —ƒ”†ƒ–͵͸Ͳšȋ‘ͲǤͷΨ˜•ǤͲǤ͵ΨȌǡƒ†ͻʹΨȋʹͶȀʹ͸Ȍ‘ˆ†‹• ‘”†ƒ ‡•‘„•‡”˜‡†™‡”‡ˆ‘”
    ˜ƒ”‹ƒ–•™‹–ŠƒŽŽ‡Ž‹ ˆ”ƒ –‹‘•„‡Ž‘™–Š‡ ‘’ƒ”ƒ–‘”‘Ǥ
    •ƒ’Ž‡•ˆ”‘ʹͲͷ’ƒ–‹‡–•™‡”‡–‡•–‡†ˆ‘”–Š‡•–—†›‘ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†
    ‡š‘ʹͲ‹•‡”–‹‘•Ȍǡ‹ Ž—†‹‰•ƒ’Ž‡•ˆ”‘ƒŽŽƒ˜ƒ‹Žƒ„Ž‡•—„Œ‡ –•–‡•–‡†‹–Š‡ƒ••‘ ‹ƒ–‡† Ž‹‹ ƒŽ
    •–—†›™‹–Š•—ˆˆ‹ ‹‡–”‡ƒ–ƒ–‡”‹ƒŽˆ‘”–‡•–‹‰™‹–Š–Š‡ ‘’ƒ”ƒ–‘”‡–Š‘†Ǥ‘•ƒ’Ž‡•ˆƒ‹Ž‡†
    –‡•–‹‰‘–Š‡ ‘’ƒ”ƒ–‘”ǡ™Š‹Ž‡–™‘•ƒ’Ž‡•ˆƒ‹Ž‡†–‡•–‹‰‘ —ƒ”†ƒ–͵͸Ͳšƒ†™‡”‡‡š Ž—†‡†
    ˆ”‘–Š‡•—„•‡“—‡–ƒƒŽ›•‹•Ǥƒ†ƒ”‡”‡’‘”–‡†‹Table 5„‡Ž‘™Ǥ

    Table 5. Summary of Concordance Between Guardant360 CDx and NGS Comparator Method #2
    Guardant360 Guardant360 Guardant360 Guardant360
    CDx(+), CDx(+), CDx(-), CDx(-),
    Alteration Comparator Comparator Comparator Comparator Patients PPA NPA
    Type #2 (+) #2 (-) #2 (+) #2 (-) (n) (95% CI) (95% CI)

    EGFR‡š‘ ͺͲ ʹͷ ͳ ͳ͸͸ ʹ͹ʹ ͻͺǤ͹͸Ψ ͺ͸ǤͻͳΨ


    ʹͲ ȋͻ͵Ǥ͵ͳΨǡ ȋͺͳǤʹͻΨǡ
    ‹•‡”–‹‘• ͻͻǤͻ͸ΨȌ ͻͳǤ͵ͷΨȌ

    ERBB2 ͺͷ ͳͲ ͳ ͳͲ͹ ʹͲ͵ ͻͺǤͺΨ ͻͳǤͷΨ


    ƒ –‹˜ƒ–‹‰ ȋͻ͵Ǥ͹Ψǡ ȋͺͶǤͺΨǡ
    —–ƒ–‹‘• ͳͲͲǤͲΨȌ ͻͷǤͺΨȐ
    ȋ•ƒ†
    ‡š‘ʹͲ
    ‹•‡”–‹‘• 

    ͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    c. Concordance - Comparison to Mass Spectrometry-Based Comparator Method #3
    ƒƒŽ›–‹ ƒŽƒ —”ƒ ›•–—†›™ƒ•’‡”ˆ‘”‡†™‹–Š’Žƒ•ƒ Ž‹‹ ƒŽ•’‡ ‹‡•ȋͳͲ͸KRAS ͳʹ
    —–ƒ–‹‘Ǧ’‘•‹–‹˜‡’ƒ–‹‡–•ƒ†ͳͲ͹KRAS ͳʹ—–ƒ–‹‘Ǧ‡‰ƒ–‹˜‡’ƒ–‹‡–•Ȍˆ”‘’ƒ–‹‡–•–‘
    †‡‘•–”ƒ–‡–Š‡ ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†ƒ‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡†ƒ••
    •’‡ –”‘‡–”›Ǧ„ƒ•‡† ‘’ƒ”ƒ–‘”ƒ••ƒ›ˆ‘”–Š‡†‡–‡ –‹‘‘ˆKRAS ͳʹǤŠ‹••–—†›‡˜ƒŽ—ƒ–‡†ƒ•‡–‘ˆ
    ʹͳͶ’Žƒ•ƒ•’‡ ‹‡•ˆ”‘–Š”‡‡ȋ͵Ȍ ‘Š‘”–•ǡ‹ Ž—†‹‰ͷ͵•ƒ’Ž‡•’‘•‹–‹˜‡ˆ‘”KRAS
    ͳʹ—–ƒ–‹‘„›–‹••—‡–‡•–‹‰ˆ”‘–Š‡ Ž‹‹ ƒŽ•–—†›ȋ ‘Š‘”–ͳȌǡͷ͵•ƒ’Ž‡•‘„–ƒ‹‡†
    ™‹–Š‘—– ‘•‹†‡”ƒ–‹‘ˆ‘”„‹‘ƒ”‡”•–ƒ–—•ˆ”‘–Š‡ Ž‹‹ ƒŽ•‡•‹–‹˜‹–›•–—†›ȋ ‘Š‘”–ʹȌǡ͸ͻ
    •ƒ’Ž‡•’‘•‹–‹˜‡ˆ‘”KRAS ͳʹ—–ƒ–‹‘„› —ƒ”†ƒ–͵͸Ͳˆ”‘–Š‡ —ƒ”†ƒ– ‡ƒŽ–Š„‹‘„ƒ‘ˆ
    ’”‡˜‹‘—•Ž› ‘ŽŽ‡ –‡†•ƒ’Ž‡•ȋ ‘Š‘”–͵Ȍǡƒ†͵ͻ•ƒ’Ž‡••‡Ž‡ –‡†™‹–Š‘—– ‘•‹†‡”ƒ–‹‘ˆ‘”
    „‹‘ƒ”‡”•–ƒ–—•ˆ”‘–Š‡ —ƒ”†ƒ– ‡ƒŽ–Š„‹‘„ƒȋ ‘Š‘”–͵ȌǤ‡•ƒ’Ž‡ˆƒ‹Ž‡†‡–”‹ •‘
    —ƒ”†ƒ–͵͸Ͳšǡ”‡•—Ž–‹‰‹ʹͳ͵‡˜ƒŽ—ƒ„Ž‡•ƒ’Ž‡•Ǥ•—ƒ”›‘ˆ’‘•‹–‹˜‡’‡” ‡–ƒ‰”‡‡‡–
    ȋȌƒ†‡‰ƒ–‹˜‡’‡” ‡–ƒ‰”‡‡‡–ȋȌƒ† ‘””‡•’‘†‹‰–™‘Ǧ•‹†‡†Ž‘’’‡”Ǧ‡ƒ”•‘ͻͷΨ
    ‘ˆ‹†‡ ‡‹–‡”˜ƒŽ•ȋ •Ȍ‹•’”‘˜‹†‡†‹Table 6Ǥ
    Š‡ ‘ ‘”†ƒ ‡ˆ‘”KRAS ͳʹ—–ƒ–‹‘•™ƒ•ͻ͸Ψƒ†ͻͶΨǤŠ‡†‹• ‘”†ƒ ‡ȋͳͲ
    •ƒ’Ž‡•ȌŽ‹•–‡†‹Table 6‘ —”•‘Ž›‹•ƒ’Ž‡•™‹–Š ‹” —Žƒ–‹‰–—‘”ƒ‘—–•‡ƒ”‘”„‡Ž‘™–Š‡
    ‘ǡ™Š‹ Š”‡•—Ž–•‹•–‘ Šƒ•–‹ †‡–‡ –‹‘†—‡–‘”ƒ†‘•ƒ’Ž‹‰‡ˆˆ‡ –•ǤŠ‡”‡’‘”–‡†ƒ†
    ȋTable 6Ȍ™‡”‡‘–ƒ†Œ—•–‡†ˆ‘”–Š‡†‹•–”‹„—–‹‘‘ˆ•ƒ’Ž‡•ˆ”‘–Š‡ —ƒ”†ƒ– ‡ƒŽ–Š„‹‘„ƒ
    ‘ŽŽ‡ –‡†—•‹‰–Š‡ —ƒ”†ƒ–͵͸ͲǤ
    ƒƒŽ›–‹ ƒŽƒ —”ƒ ›•–—†›™ƒ•’‡”ˆ‘”‡†ˆ‘”ESR1—–ƒ–‹‘•™‹–Šʹͷͻ•ƒ’Ž‡•ˆ”‘’ƒ–‹‡–•‹
    –Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ•–—†›•‡Ž‡ –‡†™‹–Š‘—–”‡ˆ‡”‡ ‡–‘„‹‘ƒ”‡”•–ƒ–—•ǤŽŽ•ƒ’Ž‡•™‡”‡
    –‡•–‡†„›„‘–Š —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡† ‘’ƒ”ƒ–‘”‡–Š‘†ǤŽ‹‰‹„Ž‡ESR1
    —–ƒ–‹‘•™‡”‡†‡–‡ –‡†‹ͳͶͳ‘—–‘ˆʹͷͶ•ƒ’Ž‡•ȋͷͷǤͷΨȌˆ‘” —ƒ”†ƒ–͵͸Ͳšȋ™Š‹ Š‡š Ž—†‡†
    ‘‡ˆƒ‹Ž—”‡ƒ†–™‘’ƒ‹”•‘ˆ†—’Ž‹ ƒ–‡†•ƒ’Ž‡•Ȍǡƒ†ͳʹͶ‘—–‘ˆʹͷͶ•ƒ’Ž‡•ȋͶͺǤͺΨȌˆ‘”–Š‡
    ‘’ƒ”ƒ–‘”‡–Š‘†ǤŠ‡ƒƒŽ›•‡•‘Ž›‹ Ž—†‡†‘Ǧ†—’Ž‹ ƒ–‡†•ƒ’Ž‡•–Šƒ–’ƒ••‡†‘„‘–Š
    ’Žƒ–ˆ‘”•ȋαʹͷͶȌǤTable 6•—ƒ”‹œ‡•–Š‡•ƒ’Ž‡ǦŽ‡˜‡Žƒ‰”‡‡‡–„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†
    –Š‡ ‘’ƒ”ƒ–‘”‡–Š‘†Ǥ

    Table 6. Summary of Concordance Between Guardant360 CDx and Comparator Method #3


    Guardant360 Guardant360 Guardant360 Guardant360
    CDx (+), CDx (+), CDx (-), CDx (-), PPA NPA PPV NPV
    Alteration Comparator Comparator Comparator Comparator Patients (95% (95% (95% (95%
    Type (+) (-) (+) (-) (n) CI) CI) CI) CI)
    ESR1 ͳʹͳ ʹͲ ͵ ͳͳͲ ʹͷͶ ͻͺΨ ͺͷΨ ͺ͸Ψ ͻ͹Ψ
    —–ƒ–‹‘• ȋͻ͵Ψǡ ȋ͹͹Ψǡ ȋ͹ͻΨǡ ȋͻ͵Ψǡ
    ͻͻΨȌ ͻͲΨȌ ͻͳΨȌ ͻͻΨȌ
    KRAS ͳʹ ͳͲʹ ͸ Ͷ ͳͲͳ ʹͳ͵ ͻ͸Ψ ͻͶΨ ͻͶΨ ͻ͸Ψ
    ȋͻͳΨǡ ȋͺͺΨǡ ȋͺͺΨǡ ȋͻͳΨǡ
    ͻͻΨȌ ͻͺΨȌ ͻͺΨȌ ͻͻΨȌ

    ‘ˆ—”–Š‡”‹˜‡•–‹‰ƒ–‡–Š‡‘”‹‰‹‘ˆ–Š‡•‹š —ƒ”†ƒ–͵͸Ͳš Ϊ‘’ƒ”ƒ–‘”Ȃ•ƒ’Ž‡•ˆ‘”KRAS ͳʹǡ


    ƒ‰”‡‡‡–„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡ ‘’ƒ”ƒ–‘”ƒ••ƒ›™ƒ• ƒŽ —Žƒ–‡†ˆ‘”‡ƒ Š•ƒ’Ž‡
    •‘—” ‡‹†‡’‡†‡–Ž›ȋTable 7 Ǥ••Š‘™‹ Table 7ǡƒŽŽ•‹š —ƒ”†ƒ–͵͸ͲšΪ‘’ƒ”ƒ–‘”Ȃ
    †‹• ‘”†ƒ–•ƒ’Ž‡•™‡”‡ˆ”‘ ‘Š‘”–•‡”‹ Š‡†ˆ‘”KRAS ͳʹǡ‹ Ž—†‹‰ˆ‘—”’‘•‹–‹˜‡•ƒ’Ž‡•ˆ”‘
    –Š‡ —ƒ”†ƒ– ‡ƒŽ–Š„‹‘„ƒƒ†–™‘’‘•‹–‹˜‡•ƒ’Ž‡•ˆ”‘–Š‡ Ž‹‹ ƒŽ•–—†›Ǥ

    ͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 7. Summary of Concordance Between Guardant360 CDx and Comparator for KRAS G12C
    by Cohort
    Guardant360 Guardant360 Guardant360 Guardant360 PPA NPA PPV NPV
    Sample CDx (+), CDx (+), CDx (-), CDx (-), (95% (95% (95% (95%
    Cohort Comparator (+) Comparator (-) Comparator (+) Comparator (-) CI) CI) CI) CI)
    ̴  ͵ͻ ʹ ͳ ͳͳ ͻͺΨ ͺͷΨ ͻͷΨ ͻʹΨ
    ȋαͷ͵Ȍ ȋͺ͹Ψǡ ȋͷͷΨǡ ȋͺͶΨǡ ȋ͸ʹΨǡ
    ͳͲͲΨȌ ͻͺΨȌ ͻͻΨȌ ͳͲͲΨȌ
    ̴ ͵ Ͳ Ͳ ͷͲ ͳͲͲΨ ͳͲͲΨ ͳͲͲΨ ͳͲͲΨ
    ”‡˜ƒŽ‡ ‡ ȋʹͻΨǡ ȋͻ͵Ψǡ ȋʹͻΨǡ ȋͻ͵Ψǡ
    ȋαͷ͵Ȍ ͳͲͲΨȌ ͳͲͲΨȌ ͳͲͲΨȌ ͳͲͲΨȌ
    Ǧ‹‘„ƒǦ ͵ Ͳ Ͳ ͵͸ ͳͲͲΨ ͳͲͲΨ ͳͲͲΨ ͳͲͲΨ
    •‡Ž‡ –‡† ȋʹͻΨǡ ȋͻͲΨǡ ȋʹͻΨǡ ȋͻͲΨǡ
    ȋα͵ͻȌ ͳͲͲΨȌ ͳͲͲΨȌ ͳͲͲΨȌ ͳͲͲΨȌ
    Ǧ‹‘„ƒǦ ͷ͹ Ͷ ͵ Ͷ ͻͷΨ ͷͲΨ ͻ͵Ψ ͷ͹Ψ
    ‘•‹–‹˜‡ ȋͺ͸Ψǡ ȋͳ͸Ψǡ ȋͺͶΨǡ ȋͳͺΨǡ
    ȋα͸ͺȌ ͻͻΨȌ ͺͶΨȌ ͻͺΨȌ ͻͲΨȌ
    ‘–‡ǣȀƒ†Ȁ™‡”‡‘–ƒ†Œ—•–‡†ˆ‘”–Š‡†‹•–”‹„—–‹‘‘ˆ•ƒ’Ž‡•‹–Š‡ƒ —”ƒ ›•–—†›Ǥ

    ͸ǤʹǤ ‘–”‹˜‡†ƒ’Ž‡ — –‹‘ƒŽŠƒ”ƒ –‡”‹œƒ–‹‘ȋ  Ȍ–—†›


     •–—†›™ƒ•’‡”ˆ‘”‡†–‘†‡‘•–”ƒ–‡ ‘’ƒ”ƒ„Ž‡’‡”ˆ‘”ƒ ‡„‡–™‡‡ ‘–”‹˜‡†•ƒ’Ž‡•
    –Šƒ– ‘•‹•–‡†‘ˆˆ—•‹‘ ‡ŽŽŽ‹‡ ˆƒ–‡”‹ƒŽƒ†ˆ—•‹‘’‘•‹–‹˜‡ Ž‹‹ ƒŽ•ƒ’Ž‡ ˆƒ–‡”‹ƒŽǤ
    Š‡ •–—†›™ƒ•’‡”ˆ‘”‡†—•‹‰ͷ‰‹’—–ȋ–Š‡Ž‘™‡•– ˆ‹’—–ˆ‘”–Š‡ƒ••ƒ›Ȍ–‘
    ‘’ƒ”‡–Š‡’‡”ˆ‘”ƒ ‡‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš™‹–Š ˆ†‡”‹˜‡†ˆ”‘ ‡ŽŽŽ‹‡•ƒ† ˆ
    †‡”‹˜‡†ˆ”‘—Ž–‹’Ž‡ Ž‹‹ ƒŽ•ƒ’Ž‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”–›’‡•™‹–ŠALKǡNTRK1ǡRETǡƒ†ROS1
    ˆ—•‹‘•ǤŠ‡ ‡ŽŽŽ‹‡ƒ† Ž‹‹ ƒŽ ˆ•ƒ’Ž‡’‘‘Ž• ‘–ƒ‹‡†‘™ˆ—•‹‘‡˜‡–•–Šƒ–™‡”‡
    †‹Ž—–‡†™‹–Š’‘‘Ž•‘ˆ™‹Ž†Ǧ–›’‡  Ȍ ˆˆ”‘—Ž–‹’Ž‡ Ž‹‹ ƒŽ•’‡ ‹‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”
    –›’‡•–‘’”‡Ǧ†‡–‡”‹‡† Ž‡˜‡Ž•ȋ–ƒ”‰‡–‡†Ž‡˜‡Ž•™‡”‡ƒ„‘˜‡ƒ†„‡Ž‘™‘Ǣ•‡‡Table 8 Ǥ‡ŽŽ
    Ž‹‡ ˆ•ƒ’Ž‡’‘‘Ž•™‡”‡–‡•–‡†ƒ ”‘••ͳ͵ǦʹͲ”‡’Ž‹ ƒ–‡•ǡͳ͵”‡’Ž‹ ƒ–‡•ˆ‘”Ž‡˜‡Ž͸ǡͳͶ”‡’Ž‹ ƒ–‡•
    ˆ‘”Ž‡˜‡Žʹǡƒ†ʹͲ”‡’Ž‹ ƒ–‡•ˆ‘”–Š‡‘–Š‡”Ž‡˜‡Ž•ƒ–ͷ‰ ˆ‹’—–ǤŽ‹‹ ƒŽ ˆ•ƒ’Ž‡’‘‘Ž•ˆ”‘
    —Ž–‹’Ž‡ ƒ ‡”–›’‡•™‡”‡–‡•–‡†™‹–ŠͳͶ”‡’Ž‹ ƒ–‡•ƒ–ͷ‰ ˆ‹’—–Ǥ‘–Š ‡ŽŽŽ‹‡ƒ† Ž‹‹ ƒŽ
    ˆ•ƒ’Ž‡’‘‘Ž•™‡”‡–‡•–‡†™‹–Šƒ‘”–Š‘‰‘ƒŽ‡–Š‘†–‘ ‘ˆ‹” Ž‡˜‡ŽǤ‡–‡ –‹‘”ƒ–‡•‘ˆ
    –Š‡Ͷˆ—•‹‘•ǡˆ‘”‡ƒ Š–‹–”ƒ–‹‘Ž‡˜‡Žǡƒ†ˆ‘”‡ƒ Š‘ˆ–Š‡–™‘–›’‡•‘ˆ’‘‘Ž•ǡƒ”‡’”‡•‡–‡†‹Table 8Ǥ
    ƒ•‡†‘–Š‡•‡ƒƒŽ›•‡•ǡ–Š‡”‡•—Ž–•†‡‘•–”ƒ–‡–Šƒ––Š‡’‡”ˆ‘”ƒ ‡‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš‹•
    •‹‹Žƒ”ˆ‘”„‘–Šˆ—•‹‘’‘•‹–‹˜‡ ‘–”‹˜‡† ˆ•ƒ’Ž‡•ƒ†ˆ‘”ˆ—•‹‘’‘•‹–‹˜‡ Ž‹‹ ƒŽ ˆ
    •ƒ’Ž‡•Ǥ

    Table 8. Fusion Detection Rate in the CSFC study


    Detection Rate (95% confidence interval)
    Level 1 Level 2 Level 3 Level 4 Level 5 Level 6
    Sample Target MAF Target MAF Target MAF Target MAF Target MAF Target MAF
    Fusion Type 0.07% 0.175% 0.35% 0.7% 1.4% 1.8%
    EML4ǦALK ‡ŽŽŽ‹‡ ͷǤͲΨ ʹͺǤ͸Ψ ͷͲǤͲΨ ͻͲǤͲΨ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    ȋͲǤͳΨǡ ȋͺǤͶΨǡ ȋʹ͹ǤʹΨǡ ȋ͸ͺǤ͵Ψǡ ȋͺ͵ǤʹΨǡ ȋ͹ͷǤ͵Ψǡ
    ʹͶǤͻΨȌ ͷͺǤͳΨȌ ͹ʹǤͺΨȌ ͻͺǤͺΨȌ ͳͲͲǤͲΨȌ ͳͲͲΨȌ
    EML4ǦALK Ž‹‹ ƒŽ ͹ǤͳΨ ʹͺǤ͸Ψ ͷͲǤͲΨ ͺͷǤ͹Ψ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    ȋͲǤʹΨǡ ȋͺǤͶΨǡ ȋʹ͵ǤͲΨǡ ȋͷ͹ǤʹΨǡ ȋ͹͸ǤͺΨǡ ȋ͹͸ǤͺΨǡ
    ͵͵ǤͻΨȌ ͷͺǤͳΨȌ ͹͹ǤͲΨȌ ͻͺǤʹΨȌ ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    CCDC6ǦRET ‡ŽŽŽ‹‡ ͳͷǤͲΨ ͵ͷǤ͹Ψ ͺͲǤͲΨ ͻͷǤͲΨ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    ȋ͵ǤʹΨǡ ȋͳʹǤͺΨǡ ȋͷ͸Ǥ͵Ψǡ ȋ͹ͷǤͳΨǡ ȋͺ͵ǤʹΨǡ ȋ͹ͷǤ͵Ψǡ
    ͵͹ǤͻΨȌ ͸ͶǤͻΨȌ ͻͶǤ͵ΨȌ ͻͻǤͻΨȌ ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    ͳͲ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Detection Rate (95% confidence interval)
    Level 1 Level 2 Level 3 Level 4 Level 5 Level 6
    Sample Target MAF Target MAF Target MAF Target MAF Target MAF Target MAF
    Fusion Type 0.07% 0.175% 0.35% 0.7% 1.4% 1.8%
    TRIM33Ǧ Ž‹‹ ƒŽ ͹ǤͳΨ ͳͶǤ͵Ψ ͸ͶǤ͵Ψ ͺͷǤ͹Ψ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    RET ȋͲǤʹΨǡ ȋͳǤͺΨǡ ȋ͵ͷǤͳΨǡ ȋͷ͹ǤʹΨǡ ȋ͹͸ǤͺΨǡ ȋ͹͸ǤͺΨǡ
    ͵͵ǤͻΨȌ ͶʹǤͺΨȌ ͺ͹ǤʹΨȌ ͻͺǤʹΨȌ ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    ROS1Ǧ ‡ŽŽŽ‹‡ ͲǤͲΨ ʹͳǤͶΨ ͷͲǤͲΨ ͹ͷǤͲΨ ͳͲͲΨ ͳͲͲǤͲΨ
    SLC34A2 ȋͲǤͲΨǡ ȋͶǤ͹Ψǡ ȋʹ͹ǤʹΨǡ ȋͷͲǤͻΨǡ ȋͺ͵ǤʹΨǡ ȋ͹ͷǤ͵Ψǡ
    ͳ͸ǤͺΨȌ ͷͲǤͺΨȌ ͹ʹǤͺΨȌ ͻͳǤ͵ΨȌ ͳͲͲǤͲΨȌ ͳͲͲΨȌ
    ROS1ǦCD74 Ž‹‹ ƒŽ ͹ǤͳΨ ͶʹǤͻΨ ͺͷǤ͹Ψ ͳͲͲǤͲΨ ͳͲͲǤͲΨ 
    ȋͲǤʹΨǡ ȋͳ͹Ǥ͹Ψǡ ȋͷ͹ǤʹΨǡ ȋ͹͸ǤͺΨǡ ȋͺ͵ǤͻΨǡ
    ͵͵ǤͻΨȌ ͹ͳǤͳΨȌ ͻͺǤʹΨȌ ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    TPM3Ǧ ‡ŽŽŽ‹‡ ͳͷǤͲΨ ͷͲǤͲΨ ͶͲǤͲΨ ͻͲǤͲΨ ͳͲͲǤͲΨ ͳͲͲǤͲΨ
    NTRK1 ȋ͵ǤʹΨǡ ȋʹ͵ǤͲΨǡ ȋͳͻǤͳΨǡ ȋ͸ͺǤ͵Ψǡ ȋͺ͵ǤʹΨǡ ȋ͹ͷǤ͵Ψǡ
    ͵͹ǤͻΨȌ ͹͹ǤͲΨȌ ͸͵ǤͻΨȌ ͻͺǤͺΨȌ ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    PLEKHA6Ǧ Ž‹‹ ƒŽ ʹͳǤͶΨ ͵ͷǤ͹Ψ ͺͷǤ͹Ψ ͳͲͲǤͲΨ  ͳͲͲǤͲΨ
    NTRK1 ȋͶǤ͹Ψǡ ȋͳʹǤͺΨǡ ȋͷ͹ǤʹΨǡ ȋ͹͸ǤͺΨǡ ȋ͹͸ǤͺΨǡ
    ͷͲǤͺΨȌ ͸ͶǤͻΨȌ ͻͺǤʹΨȌ ͳͲͲǤͲΨȌ ͳͲͲǤͲΨȌ
    ǣ‘–†‡–‡”‹‡†

    ͸Ǥ͵Ǥ ƒŽ›–‹ ƒŽ‡•‹–‹˜‹–›

    a. Limit of Blank (LoB)


    Š‡‘™ƒ•‡•–ƒ„Ž‹•Š‡†„›‡˜ƒŽ—ƒ–‹‰™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡•ˆ”‘Š‡ƒŽ–Š›ƒ‰‡Ǧƒ– Š‡††‘‘”
    •ƒ’Ž‡•Ǥ‹š–›Ǧ–™‘ȋ͸ʹȌ†‘‘”•ƒ’Ž‡• ‘ˆ‹”‡†–‘„‡—–ƒ–‹‘‡‰ƒ–‹˜‡„ƒ•‡†‘•‡“—‡ ‹‰™‹–Š
    ƒ‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡†‘”–Š‘‰‘ƒŽ‡–Š‘†™‡”‡’”‘ ‡••‡†—•‹‰͵Ͳ‰‘ˆ ˆ‹’—–™‹–Š–Š‡
    —ƒ”†ƒ–͵͸ͲšȋŠ‹‰Š‡•–‹’—–ˆ‘”–Š‡ƒ••ƒ›Ȍƒ ”‘••–Š”‡‡Ž‘–•‘ˆ”‡ƒ‰‡–•ǡ‘’‡”ƒ–‘”‰”‘—’•ǡ
    ƒ†‹•–”—‡–•Ǥˆ–Š‡͸ʹ†‘‘”•ƒ’Ž‡•ǡͷͺ†‘‘”•ƒ’Ž‡•™‡”‡–‡•–‡†™‹–ŠͶ”‡’Ž‹ ƒ–‡•ǡ™Š‹Ž‡Ͷ
    †‘‘”•™‡”‡–‡•–‡†™‹–Šʹ”‡’Ž‹ ƒ–‡•ˆ‘”ƒ–‘–ƒŽ‘ˆʹͶͲ”‡’Ž‹ ƒ–‡•ƒƒŽ›œ‡†–‘ƒ••‡••–Š‡ˆƒŽ•‡’‘•‹–‹˜‡
    ”ƒ–‡‘ˆ —ƒ”†ƒ–͵͸ͲšǤŠ‹••–—†›†‡‘•–”ƒ–‡†ƒ‡ƒ”œ‡”‘ˆƒŽ•‡’‘•‹–‹˜‡”ƒ–‡ƒ ”‘••–Š‡‡–‹”‡
    ”‡’‘”–ƒ„Ž‡”ƒ‰‡ǡƒ••Š‘™‹Table 9ǤŠ‡ˆƒŽ•‡’‘•‹–‹˜‡”ƒ–‡™ƒ•œ‡”‘ˆ‘”ƒ–‡‰‘”›ͳȋšȌƒ†
    ƒ–‡‰‘”›ʹ˜ƒ”‹ƒ–•Ǥ

    Table 9. LoB Study Summary Results


    Category Per Position False Positive Rate Per Sample False Positive Rate
    ƒ–‡‰‘”›ͳǣEGFRͺͷͺ ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ–‡‰‘”›ͳǣEGFR͹ͻͲ ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ–‡‰‘”›ͳǣEGFR‡š‘ͳͻ†‡Ž‡–‹‘• ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ–‡‰‘”›ͳǣEGFR‡š‘ʹͲ‹•‡”–‹‘• ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ–‡‰‘”›ͳǣERBB2 ƒ –‹˜ƒ–‹‰—–ƒ–‹‘• ͲΨ ͲȋͲȀʹͶͲȌ
    ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ
    ƒ–‡‰‘”›ͳǣESR1—–ƒ–‹‘• ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ–‡‰‘”›ͳǣKRAS ͳʹ ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ–‡‰‘”›ʹ ͲΨ ͲȋͲȀʹͶͲȌ
    ƒ‡ŽǦ™‹†‡•ȋ͵ͺǡͷ͸Ͳ„’  δͲǤͲͲͲͲͷΨ ͳǤ͸͹ΨȋͶȀʹͶͲȌ
    ƒ‡ŽǦ™‹†‡ †‡Ž•ȋͶͶǡͳͷͲ„’Ȍ δͲǤͲͲͲͲʹΨ ͲǤͺ͵ΨȋʹȀʹͶͲȌ
    ƒ‡ŽǦ™‹†‡•ȋʹ‰‡‡•Ȍ ͲǤʹΨ ͲǤͶʹΨȋͳȀʹͶͲȌ
    ƒ‡ŽǦ™‹†‡ —•‹‘•ȋͶ‰‡‡•Ȍ ͲΨ ͲȋͲȀʹͶͲȌ

    ͳͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    b. Limit of Detection (LoD)
    Š‡‘ˆ‘”–Š‡ —ƒ”†ƒ–͵͸Ͳš˜ƒ”‹ƒ–•™‹–Šš Žƒ‹•ǡ”‡’”‡•‡–ƒ–‹˜‡•ƒ†‹†‡Ž•ǡƒ†ƒŽŽ
    ”‡’‘”–ƒ„Ž‡•ƒ†ˆ—•‹‘•™ƒ•‡•–ƒ„Ž‹•Š‡†ƒ––Š‡Ž‘™‡•–ƒ†Š‹‰Š‡•– Žƒ‹‡† ˆ‹’—–ƒ‘—–•
    ȋͷƒ†͵Ͳ‰ȌǤ‘‡•–ƒ„Ž‹•Š‡†ˆ‘”ˆ—•‹‘•—•‹‰ ˆ†‡”‹˜‡†ˆ”‘ ‡ŽŽŽ‹‡•™ƒ• ‘ˆ‹”‡†ƒ–ͷ‰
    ˆ‹’—–—•‹‰ ˆ†‡”‹˜‡†ˆ”‘ Ž‹‹ ƒŽ’ƒ–‹‡–•ƒ’Ž‡•Ǥ‘•™‡”‡ˆ—”–Š‡” ‘ˆ‹”‡†‹–Š‡
    Ž‹‹ ƒŽ’‘‘Ž•‘ˆ”‡Ž‡˜ƒ– ƒ ‡”–›’‡•ˆ‘”š˜ƒ”‹ƒ–•ƒ†ƒ††‹–‹‘ƒŽ”‡’”‡•‡–ƒ–‹˜‡˜ƒ”‹ƒ–•ǡ
    ‹ Ž—†‹‰Ž‘‰‹†‡Ž•ƒ†Š‘‘’‘Ž›‡”•‹ƒ ‘„‹‡†‘ ‘ˆ‹”ƒ–‹‘ƒ†’”‡ ‹•‹‘•–—†›Ǥ
    ‘”•ǡ‹†‡Ž•ǡ‹ Ž—†‹‰š˜ƒ”‹ƒ–•ƒ†ˆ‘”•ǡ–Š‡ —ƒ”†ƒ–͵͸Ͳš‘™ƒ•‡•–ƒ„Ž‹•Š‡†„›
    ‘„‹‹‰ ˆˆ”‘ Ž‹‹ ƒŽ’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”•–‘ ”‡ƒ–‡’‘‘Ž•‘ˆƒ–‡”‹ƒŽ
    ‘’”‹•‹‰—Ž–‹’Ž‡‘™ƒŽ–‡”ƒ–‹‘•ǤŠ‡‘™ƒ•‡•–ƒ„Ž‹•Š‡†™‹–Š–Š‡•‡ Ž‹‹ ƒŽ ˆ•ƒ’Ž‡
    ’‘‘Ž•ƒ–ͷ‰ƒ†͵Ͳ‰‹’—–ǡ—•‹‰ƒ ‘„‹ƒ–‹‘‘ˆ’”‘„‹–ƒ†‡’‹”‹ ƒŽƒ’’”‘ƒ Š‡•Ǥƒ’Ž‡•™‡”‡
    –‹–”ƒ–‡†ƒ–ͷ†‹ˆˆ‡”‡– ˜ƒŽ—‡•–Šƒ–‹ Ž—†‡†Ž‡˜‡Ž•ƒ„‘˜‡ƒ†„‡Ž‘™–Š‡‘ˆ‘”•ǡƒ†‹†‡Ž•
    ‘” ‘’›—„‡”˜ƒŽ—‡•ˆ‘”•ƒ†–‡•–‡†ƒ ”‘••ʹͲ”‡’Ž‹ ƒ–‡•ˆ‘”ͷ‰‹’—–ƒ†ͳͶ”‡’Ž‹ ƒ–‡•ˆ‘”͵Ͳ
    ‰‹’—–ƒ ”‘••ƒ–Ž‡ƒ•––™‘”‡ƒ‰‡–Ž‘–•Ǥ
    Š‡‘•‘ˆˆ‘—”ȋͶȌšƒŽ–‡”ƒ–‹‘•”‡’”‡•‡–‹‰EGFR͹ͻͲǡEGFRͺͷͺǡEGFR‡š‘ͳͻ†‡Ž‡–‹‘•ǡ
    ƒ†EGFR‡š‘ʹͲ‹•‡”–‹‘•‡•–ƒ„Ž‹•Š‡†—•‹‰’‘‘Ž•‘ˆ ˆˆ”‘ Ž‹‹ ƒŽ’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘
    —Ž–‹’Ž‡ ƒ ‡”–›’‡•ƒ”‡•—ƒ”‹œ‡†‹Table 10ǤŠ‡‘™ƒ• ‘ˆ‹”‡†ˆ‘”–Š‡•‡š˜ƒ”‹ƒ–•
    —•‹‰ ˆ•ƒ’Ž‡’‘‘Ž•ˆ”‘’ƒ–‹‡–•™‹–Š‘Ž›Ǣ”‡ˆ‡”–‘Table 12„‡Ž‘™Ǥ
    Š‡‘•ˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ™‡”‡‡•–ƒ„Ž‹•Š‡†—•‹‰’‘‘Ž•
    ‘ˆ ˆˆ”‘ Ž‹‹ ƒŽ’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘’ƒ–‹‡–•ǤŠ‡‘ˆ‘”ERBB2ƒ –‹˜ƒ–‹‰
    —–ƒ–‹‘•™ƒ•‡•–ƒ„Ž‹•Š‡†–‘„‡ͳǤ͵Ψ ƒ–ͷ‰ ˆ‹’—–ƒ†ͲǤ͵Ψ ƒ–͵Ͳ‰ ˆ‹’—–
    ȋTable 10 ǤŠ‡‘•ˆ‘” ERBB2ƒ –‹˜ƒ–‹‰‡š‘ʹͲ‹•‡”–‹‘•™‡”‡‡•–ƒ„Ž‹•Š‡†–‘„‡ͳǤ͵Ψƒ†ͳǤͲΨ
     •ƒ–ͷ‰ ˆ‹’—–ˆ‘”‹•‡”–‹‘•‹œ‡•‘ˆͻ„’ƒ†ͳʹ„’ǡ”‡•’‡ –‹˜‡Ž›ǤŠ‡‘ˆ‘”ERBB2
    ƒ –‹˜ƒ–‹‰‡š‘ʹͲ‹•‡”–‹‘‘ˆͳʹ„’ƒ–͵Ͳ‰ ˆ‹’—–™ƒ•‡•–ƒ„Ž‹•Š‡†–‘„‡ͲǤͶΨ ǤŠ‡
    ERBB2ƒ –‹˜ƒ–‹‰‡š‘ʹͲ‹•‡”–‹‘‘ˆͻ„’ƒ–͵Ͳ‰ ˆ‹’—–™ƒ•‘–†‡–‡”‹‡†ƒ•ƒŽŽ†‹Ž—–‹‘•
    –‡•–‡††‘™–‘ͲǤͳΨ ™‡”‡†‡–‡ –‡†ƒ–ͳͲͲΨǤ
    Š‡‘ˆ‘”KRAS ͳʹ™ƒ•‡•–ƒ„Ž‹•Š‡†–‘„‡ͳǤͷΨ ƒ–ͷ‰ ˆ‹’—–ƒ†ͲǤͷΨ ƒ–͵Ͳ‰
    ˆ‹’—–—•‹‰’ƒ–‹‡–•ƒ’Ž‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”•ȋ Table 11ȌǤŠ‡‡•–ƒ„Ž‹•Š‡†‘™ƒ•
    ˆ—”–Š‡” ‘ˆ‹”‡†‹ Ž‹‹ ƒŽ•ƒ’Ž‡•–‘„‡ͳǤͺΨ ƒ–ͷ‰‹’—–ƒ†ͲǤͷΨ ƒ–͵Ͳ‰
    ‹’—–„›–‡•–‹‰ʹͲƒ†ͳͶ”‡’Ž‹ ƒ–‡•ǡ”‡•’‡ –‹˜‡Ž›ǡ™‹–Š͵•‡–•‘ˆ”‡ƒ‰‡–Ž‘–•ȋ Table 10 ǤŠ‡•‡
    ‘ˆ‹”‡†‘˜ƒŽ—‡•™‡”‡—–‹Ž‹œ‡†‹‘–Š‡”’‡”ˆ‘”ƒ ‡•–—†‹‡•ȋ e.g.ǡ’”‡ ‹•‹‘ǡ‰—ƒ”†„ƒ†‹‰ƒ†
    ‹–‡”ˆ‡”‡ ‡ȌǤ —”–Š‡”ǡ–Š‡‘˜ƒŽ—‡•ƒ–Š‹‰Šƒ†Ž‘™‹’—–Ž‡˜‡Ž•ˆ‘”KRAS ͳʹ™‡”‡
    ‘ˆ‹”‡†‹ƒ’”‡ ‹•‹‘•–—†›—•‹‰’ƒ–‹‡–•ƒ’Ž‡•‡ƒ”–Š‡•‡ ‘ˆ‹”‡†‘˜ƒŽ—‡•ȋ•‡‡
    Section 6.5 PrecisionȌǤ
    Š‡‘ˆ‘”ESR1—–ƒ–‹‘•™ƒ•‡•–ƒ„Ž‹•Š‡†—•‹‰•ƒ’Ž‡’‘‘Ž•’”‡’ƒ”‡†ˆ”‘ESR1—–ƒ–‹‘Ǧ
    ’‘•‹–‹˜‡„”‡ƒ•– ƒ ‡”•ƒ’Ž‡•ƒ†‹••—ƒ”‹œ‡†‹Table 10Ǥ

    Table 10. Summary of LoDs for Alterations Associated with CDx Claims using Pools of cfDNA
    from Clinical Plasma Samples
    Alteration Alteration Type LoD (5 ng input) LoD (30 ng input)
    EGFR͹ͻͲ  ͳǤͳΨ  ͲǤʹΨ 
    EGFRͺͷͺ  ͳǤͲΨ  ͲǤʹΨ 
    EGFR‡š‘ͳͻ†‡Ž‡–‹‘ ‡Ž‡–‹‘ȋͳͷ„’Ȍ ͳǤͷΨ  ͲǤʹΨ 
    EGFR‡š‘ʹͲ‹•‡”–‹‘• •‡”–‹‘• ͳǤͶΨ ȗ ͲǤ͵Ψ 
    ȋ͵ǡ͸ǡͻǡƒ†ͳʹ„’Ȍ ȋͲǤͺΨǦͳǤͺΨȌ

    ͳʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Alteration Alteration Type LoD (5 ng input) LoD (30 ng input)
    ERBB2•  ͳǤ͵Ψ ȗ  ͲǤ͵Ψ ȗ
    ȋͳǤͲΨǦͳǤͺΨȌ ȋͲǤʹΨǦͲǤͷΨȌ
    ERBB2‡š‘ʹͲ‹•‡”–‹‘• •‡”–‹‘ȋͻ„’Ȍ ͳǤ͵Ψ  
    •‡”–‹‘ȋͳʹ„’Ȍ ͳǤͲΨ  ͲǤͶΨ 
    ESR1‹••‡•‡—–ƒ–‹‘•  ͳǤͳΨ ̰ ͲǤ͵Ψ ̰
    
    KRAS ͳʹ  ͳǤͺΨ  ͲǤͷΨ 
    ȗ‡ƒ Ǥ ”ƒ‰‡•Š‘™‹’ƒ”‡–Š‡•‹•Ǥǣ‘–†‡–‡”‹‡†ǢƒŽŽ†‹Ž—–‹‘•†‘™–‘ͲǤͳΨ ™‡”‡†‡–‡ –‡†ƒ–
    ͳͲͲΨǤ
    ̰Š‡ ˜ƒŽ—‡•™‡”‡‡•–ƒ„Ž‹•Š‡†ˆ‘”’”‡˜ƒŽ‡–ESR1 —–ƒ–‹‘•ȋ͵ͺͲǡͷ͵͹ǡƒ†ͷ͵ͺ ȌǤ
    Š‡‘‡•–‹ƒ–‡•ˆ‘”ǡ‹†‡Ž•ǡƒ†ƒŽ–‡”ƒ–‹‘•‡•–ƒ„Ž‹•Š‡†—•‹‰’‘‘Ž•‘ˆ ˆˆ”‘ Ž‹‹ ƒŽ
    ’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”–›’‡•ƒ”‡•—ƒ”‹œ‡†‹Table 11.
    ‘”ˆ—•‹‘•ǡ–Š‡ —ƒ”†ƒ–͵͸Ͳš‘™ƒ•‡•–ƒ„Ž‹•Š‡†—•‹‰ ˆˆ”‘ ‡ŽŽŽ‹‡•™‹–Š‘™
    ˆ—•‹‘•–‹–”ƒ–‡†‹–‘™‹Ž†Ǧ–›’‡ȋȌ ˆˆ”‘ Ž‹‹ ƒŽ’Žƒ•ƒ•ƒ’Ž‡•Ǥƒ’Ž‡•™‡”‡–‹–”ƒ–‡†ƒ–ͷ
    †‹ˆˆ‡”‡– ˜ƒŽ—‡•ˆ‘”ˆ—•‹‘•ƒ ”‘••ʹͲ”‡’Ž‹ ƒ–‡•ˆ‘”ͷ‰ ˆ‹’—–ƒ†ͳͶ”‡’Ž‹ ƒ–‡•ˆ‘”͵Ͳ‰
    ˆ‹’—–ƒ ”‘••–™‘”‡ƒ‰‡–Ž‘–•ǤŠ‡‡•–ƒ„Ž‹•Š‡†‘™ƒ•–Š‡ ‘ˆ‹”‡†—•‹‰ˆ—•‹‘’‘•‹–‹˜‡
    ˆˆ”‘ Ž‹‹ ƒŽ’Žƒ•ƒ•ƒ’Ž‡•ƒ–ͷ‰ ˆ‹’—–‘Ž›Ǥ —•‹‘’‘•‹–‹˜‡ ˆˆ”‘ Ž‹‹ ƒŽ
    •ƒ’Ž‡•™‡”‡–‹–”ƒ–‡†ƒ ”‘••ͷ ‘ ‡–”ƒ–‹‘•™‹–ŠͳͶ”‡’Ž‹ ƒ–‡•ƒ ”‘••ʹ”‡ƒ‰‡–Ž‘–•Ǥ
    Š‡Š‹‰Š‡”‘ˆ–Š‡‘˜ƒŽ—‡•‡•–ƒ„Ž‹•Š‡†—•‹‰ ‡ŽŽŽ‹‡•ƒ† ‘ˆ‹”‡†—•‹‰ Ž‹‹ ƒŽ•ƒ’Ž‡•™‡”‡
    —•‡†–‘ Žƒ‹–Š‡‘’‡”ˆ‘”ƒ ‡Ž‡˜‡Ž•‘ˆ–Š‡–‡•–ˆ‘”ˆ—•‹‘•ƒ–ͷ‰ȋ Table 11 Ǥ

    Table 11. LoD Establishment Study Summary Results for Representative Variants using Pools
    of cfDNA Clinical Plasma Samples from Multiple Cancer Types
    Alteration Alteration Type LoD, 5 ng (MAF/CN) LoD, 30 ng (MAF/CN)
    BRAF͸ͲͲ  ͳǤͺΨ ͲǤʹΨ
    KRAS ͳʹ  ͳǤͷΨ ͲǤͷΨ
    NRAS͸ͳ  ͵ǤͲΨ ͲǤͺΨ
    ESR1͵ͺͲ  ͳǤͲΨ ͲǤ͵Ψ
    ESR1ͷ͵͹  ͳǤͲΨ ͲǤ͵Ψ
    ESR1ͷ͵ͺ  ͳǤͳΨ ͲǤʹΨ
    BRCA1ʹ͵ˆ• ‡Ž‡–‹‘ȋʹ„’Ȍ ʹǤ͸Ψ ͲǤͺΨ
    BRCA2ͳͻͺʹˆ• ‡Ž‡–‹‘ȋͳ„’Ȍ ͳǤ͵Ψ ͲǤͶΨ
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋͻ„’Ȍ ͲǤͺΨ ͲǤʹΨ
    ͹͸͹̴͹͸ͻ†—’
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋͻ„’Ȍ ͳǤͶΨ ͲǤ͵Ψ
    ͹͸͹̴͹͸ͻ†—’ȗ
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋ͵„’Ȍ ͲǤͻΨ 
    ͹͹͵†—’ȗ
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋͻ„’Ȍ ͳǤͺΨ ͲǤ͵Ψ
    ͹͹ͳ̴ ͹͹͵†—’ȗ
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋ͸„’Ȍ ͳǤͷΨ 
    ͹͹ʹ̴ ͹͹͵†—’ȗ
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋͳʹ„’Ȍ ͳǤͺΨ 
    ͹͹ʹ̴ ͹͹͵‹•ȗ
    ERBB2‡š‘ʹͲ‹•‡”–‹‘ǡ •‡”–‹‘ȋͳʹ„’Ȍ ͳǤͳΨ ͲǤʹΨ
    ͹͹ͷ̴ ͹͹͸‹•
    MET  ʹǤͶ ʹǤͶ
    ERBB2  ʹǤ͵ ʹǤ͵

    ͳ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Alteration Alteration Type LoD, 5 ng (MAF/CN) LoD, 30 ng (MAF/CN)
    NTRK1 —•‹‘ ͲǤͻΨȋͲǤͻΨȌ ȋͲǤʹΨȌ
    RET —•‹‘ ͳǤͳΨȋͲǤ͹ΨȌ ȋͲǤͳΨȌ
    ROS1 —•‹‘ ͳǤͻΨȋͳǤʹΨȌ ȋͲǤʹΨȌ
    ALK —•‹‘ ͳǤͶΨȋͳǤͷΨȌ ȋͲǤʹΨȌ
    ‘–‡ǣȗ•ƒ’Ž‡’‘‘Ž„ƒ ‰”‘—†Ǥ—„‡”•‹’ƒ”‡–Š‡•‡•”‡’”‡•‡–‘‡•–ƒ„Ž‹•Š‡†—•‹‰ ‡ŽŽŽ‹‡†‡”‹˜‡† ˆǤ
     ǣ—–ƒ–ŽŽ‡Ž‡ ”ƒ –‹‘ǡǣ ‘’›—„‡”
    Š‡‡•–ƒ„Ž‹•Š‡†‘™ƒ• ‘ˆ‹”‡†ˆ‘”š˜ƒ”‹ƒ–•„›–‡•–‹‰ Ž‹‹ ƒŽ’ƒ–‹‡–’‘‘Ž•‡š Ž—•‹˜‡Ž›ˆ”‘
    ’ƒ–‹‡–•–ƒ”‰‡–‹‰ͳǦͳǤͷš‘‘ˆ–Š‡‡•–ƒ„Ž‹•Š‡†‘ȋ”‡ˆ‡”–‘Table 12 ƒ ”‘••ƒ–Ž‡ƒ•–ʹͲ
    ”‡’Ž‹ ƒ–‡•ƒ–ͷ‰‹’—–—•‹‰ƒ ‘„‹‡†‘‘ˆ‹”ƒ–‹‘ƒ†”‡ ‹•‹‘–—†›Ǥ‹‹Žƒ”Ž›ǡ–Š‡
    ‡•–ƒ„Ž‹•Š‡†‘™ƒ• ‘ˆ‹”‡†ˆ‘”•ƒ†‹†‡Ž•‹ Ž‹‹ ƒŽ’‘‘Ž•ƒ†‡‡š Ž—•‹˜‡Ž›ˆ”‘–Š‡
    ”‡Ž‡˜ƒ– ƒ ‡”–›’‡•‘—” ‡ƒ–‡”‹ƒŽ’”‡’ƒ”‡†™‹–Šͷ‰ ˆ‹’—––ƒ”‰‡–‹‰ͳǦͳǤͷš‘ƒ†”—‹
    ƒ–Ž‡ƒ•–ʹͲ”‡’Ž‹ ƒ–‡•–ƒ”‰‡–‹‰ͷ†‹•–‹ –˜ƒ”‹ƒ–•Ǥ•–ƒ„Ž‹•Š‡†‘–ƒ”‰‡–•™‡”‡—•‡†ˆ‘”ͷ˜ƒ”‹ƒ–•
    ȋEGFRͺͷͺǡEGFR͹ͻͲǡEGFR‡š‘ͳͻ†‡Ž‡–‹‘ǡ͹Ͷ͸̴͹ͷͲ†‡ŽǡKRAS ͳʹǡƒ†ROS1ˆ—•‹‘•Ȍǡ
    ™Š‹Ž‡in silico‘–ƒ”‰‡–•™‡”‡—•‡†ˆ‘”ͳͲƒ††‹–‹‘ƒŽ˜ƒ”‹ƒ–•–‘–ƒ”‰‡–˜ƒ”‹ƒ–•–‘ͳǦͳǤͷš‘Ǥ
    –Š‹• ‘„‹‡†‘ƒ†”‡ ‹•‹‘•–—†›ǡȋ•‡‡Section 6.5 Precision „‡Ž‘™ˆ‘”ƒ††‹–‹‘ƒŽ•–—†‹‡•
    †‡‘•–”ƒ–‹‰ƒ••ƒ›’”‡ ‹•‹‘•–ƒ”–‹‰ˆ”‘ ˆ‡š–”ƒ –‹‘ǡƒ†™‹–Šƒ††‹–‹‘ƒŽ—–ƒ–‹‘’‘•‹–‹˜‡
    ƒ†‡‰ƒ–‹˜‡•ƒ’Ž‡•Ȍ•ƒ’Ž‡•™‡”‡–‡•–‡†ƒ ”‘••–Š”‡‡’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•–Šƒ–‡˜ƒŽ—ƒ–‡†–Š”‡‡
    ‘’‡”ƒ–‘”‰”‘—’•ǡ–Š”‡‡‹•–”—‡– ‘„‹ƒ–‹‘•ǡƒ†–Š”‡‡”‡ƒ‰‡–Ž‘–•‘˜‡”ƒ–Ž‡ƒ•––Š”‡‡
    †‹ˆˆ‡”‡–•–ƒ”–†ƒ–‡•Ǥ
    Š‡Š‹‰Š‡”‘ˆ–Š‡‘˜ƒŽ—‡•‡•–ƒ„Ž‹•Š‡†—•‹‰ Ž‹‹ ƒŽ•ƒ’Ž‡’‘‘Ž•ˆ”‘ ƒ ‡”’ƒ–‹‡–•ƒ†
    ‘ˆ‹”‡†—•‹‰ Ž‹‹ ƒŽ•ƒ’Ž‡•‡š Ž—•‹˜‡Ž›ˆ”‘–Š‡”‡Ž‡˜ƒ– ƒ ‡”–›’‡•‘—” ‡ƒ–‡”‹ƒŽ™‡”‡—•‡†
    –‘ Žƒ‹‘’‡”ˆ‘”ƒ ‡‘ˆ–Š‡–‡•–ƒ–ͷ‰‹’—–ƒ••—ƒ”‹œ‡†‹Table 12Ǥ

    Table 12. Combined LoD Confirmation and Precision Study Summary Results for CDx Variants
    and Representative Variants
    Number Positive
    / Number
    Alteration MAF Alteration Type Cancer Type Expected PPA
    EGFRͺͷͺ ͳǤͷΨȗ   ʹͲȀʹͲ ͳͲͲǤͲΨ
    EGFR͹ͻͲ ͳǤͶΨȗ   ͳͻȀʹͲ ͻͷǤͲΨ
    EGFR‡š‘ͳͻ†‡Ž‡–‹‘ǡ ͳǤͷΨȗ ‡Ž‡–‹‘ȋͳͷ„’Ȍ  ʹͲȀʹͲ ͳͲͲǤͲΨ
    ͹Ͷ͸̴͹ͷͲ†‡Ž
    EGFR‡š‘ͳͻ†‡Ž‡–‹‘ǡ ʹǤ͵Ψ̰ ‡Ž‡–‹‘ȋʹͻ„’Ȍ  ʹͲȀʹͲ ͳͲͲǤͲΨ
    ͹ͷͲ̴ ͹ͷͻ†‡Ž‹•
    KIT͸ͷͶ ʹǤͷΨ̰  ”‘•–ƒ–‡ ʹͲȀʹͲ ͳͲͲǤͲΨ
    KRAS ͳʹ ͳǤͺΨȗ   ͳͻȀʹͲ ͻͷǤͲΨ
    PIK3CAͷͶͷ ʹǤͶΨ̰  ”‡ƒ•– ʹͳȀʹͳ ͳͲͲǤͲΨ
    PIK3CA ͳͲͶ͹ ͳǤ͹Ψ̰  ”‡ƒ•– ʹͳȀʹͳ ͳͲͲǤͲΨ
    ESR1͵ͺͲ ͳǤͲΨȗȗ  ”‡ƒ•– ʹͶȀʹͶ ͳͲͲǤͲΨ
    ESR1ͷ͵͹ ͳǤͲΨȗȗ  ”‡ƒ•– ʹ͵ȀʹͶ ͻͷǤͺΨ
    ESR1ͷ͵ͺ ͳǤͳΨȗȗ  ”‡ƒ•– ʹ͵ȀʹͶ ͻͷǤͺΨ
    ESR1 ͶͶʹ ʹǤ͵Ψ̰  ”‡ƒ•– ʹͶȀʹͶ ͳͲͲǤͲΨ
    ESR1Ͷ͵͸ ʹǤͺΨ̰  ”‡ƒ•– ʹͶȀʹͶ ͳͲͲǤͲΨ
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ ͳǤͶΨ •‡”–‹‘ȋͻ„’Ȍ  ͶͳȀͶʹ ͻ͹Ǥ͸Ψ
    ͹͸͹̴ ͹͸ͻ†—’
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ ͲǤͻΨȗȗ •‡”–‹‘ȋ͵„’Ȍ  ͶͳȀͶʹ ͻ͹Ǥ͸Ψ
    ͹͹͵†—’

    ͳͶ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Number Positive
    / Number
    Alteration MAF Alteration Type Cancer Type Expected PPA
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ ͳǤͺΨȗȗ •‡”–‹‘ȋͻ„’Ȍ  ͶͳȀͶͳ ͳͲͲΨ
    ͹͹ͳ̴ ͹͹͵†—’
    EGFR‡š‘ʹͲ‹•‡”–‹‘ǡ ͵ǤͷΨ̰ •‡”–‹‘ȋͻ„’Ȍ  ʹʹȀʹʹ ͳͲͲǤͲΨ
    ͹͹͵̴͹͹Ͷ‹•  
    MET‡š‘ͳͶ•‹’’‹‰ ʹǤ͹Ψ̰ ‡Ž‡–‹‘ȋͳͷ„’Ȍ  ʹͲȀʹͲ ͳͲͲǤͲΨ
    ͹Ǥͳͳ͸ͶͳʹͲͶͳǤ 
     ε
    BRCA2͵Ͳ͵͵ˆ• ͶǤͶΨ̰ †‡Žȋͳ„’Ȍǡ  ʹͳȀʹͳ ͳͲͲǤͲΨ
    Š‘‘’‘Ž›‡”
    BRCA2 ͸Ͳͷˆ• ͷǤͲΨ̰ †‡Žȋͳ„’Ȍǡ ”‘•–ƒ–‡ ʹͲȀʹͲ ͳͲͲǤͲΨ
    Š‘‘’‘Ž›‡”
    BRCA2ͳͷ͵ʹˆ• ͶǤʹΨ̰ †‡Žȋͳ„’Ȍǡ ”‘•–ƒ–‡ ʹͲȀʹͲ ͳͲͲǤͲΨ
    Š‘‘’‘Ž›‡”
    STK11ʹͺʹˆ• ͶǤ͹Ψ̰ †‡Žȋͳ„’Ȍǡ  ʹͳȀʹͳ ͳͲͲǤͲΨ
    Š‘‘’‘Ž›‡”
    ROS1 ͳǤͺΨȗ —•‹‘  ʹͳȀʹͳ ͳͲͲǤͲΨ
    ȗ„•‡”˜‡† Ž‡˜‡Ž‹‘‘ˆ‹”ƒ–‹‘–—†›Ǥ‘ ‘ˆ‹”‡†™‹–Š•‹‰Ž‡ ƒ ‡”–›’‡ Ž‹‹ ƒŽ’‘‘Žƒ†ηͻͷΨ†‡–‡ –‹‘
    ”ƒ–‡‹•™‹–Š‹ͳǦͳǤͷš‘ Ž‡˜‡Žˆ”‘–Š‡‘”‹‰‹ƒŽ‡•–ƒ„Ž‹•Š‡–•–—†›”ƒ‰‡Ǥ
    ȗȗ„•‡”˜‡†‘Ž‡˜‡Ž‹‘•–ƒ„Ž‹•Š‡––—†›Ǥ‘™ƒ•‡’‹”‹ ƒŽŽ›‡•–ƒ„Ž‹•Š‡†—•‹‰‘”„”‡ƒ•– ƒ ‡”’‘‘Ž•Ǥ
    ̰„•‡”˜‡† ƒ––Š‡Ž‡˜‡Ž–‡•–‡†™‹–ŠηͻͷΨ†‡–‡ –‹‘”ƒ–‡ˆ‘”˜ƒ”‹ƒ–•™‹–Š‘—–†‹”‡ –’”‹‘”‘‡•–ƒ„Ž‹•Š‡–†ƒ–ƒǤ
    ƒ‡ŽǦ™‹†‡ƒ†‹†‡Ž•†‡–‡ –‡†„› —ƒ”†ƒ–͵͸Ͳšƒ”‡•—ƒ”‹œ‡†‹Table 13ƒ•‡†‹ƒ
    ˜ƒŽ—‡•Ǥ

    Table 13. Summary of LoD for Alterations Associated with Panel-Wide Claims
    Alteration Median LoD, 5ng (MAF) Median LoD, 30ng (MAF)
    ƒ‡ŽǦ™‹†‡• ͳǤͺΨ ͲǤʹΨ
    ƒ‡ŽǦ™‹†‡ †‡Ž• ʹǤ͹Ψ ͲǤʹΨ

    ͸ǤͶǤ ƒŽ›–‹ ƒŽ’‡ ‹ˆ‹ ‹–›

    a. Endogenous and Exogenous Interfering Substances


    ‘‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ‡†‘‰‡‘—•ƒ†‹ ”‘„‹ƒŽ‹–‡”ˆ‡”‹‰•—„•–ƒ ‡•‘–Š‡
    ’‡”ˆ‘”ƒ ‡‘ˆ —ƒ”†ƒ–͵͸Ͳšǡ–Š‹••–—†›‡˜ƒŽ—ƒ–‡†™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡•ˆ”‘ƒ–‘–ƒŽ‘ˆͷͲ
    ’ƒ–‹‡–•ȋƒ–Ž‡ƒ•––‡’ƒ–‹‡–•’‡”‹–‡”ˆ‡”‹‰•—„•–ƒ ‡Ȍǡ”‡’”‡•‡–‹‰‘”‡–Šƒͳ͵ ƒ ‡”–›’‡•ǤŠ‡
    ͳ͵Ͳ•ƒ’Ž‡•–Šƒ–’ƒ••‡† Š‡ •‹ Ž—†‡†”‡’”‡•‡–ƒ–‹˜‡˜ƒ”‹ƒ–•Ǥ
    —„•–ƒ ‡•™‡”‡ ‘•‹†‡”‡†ƒ•‘Ǧ‹–‡”ˆ‡”‹‰‹ˆǡ™Š‡ ‘’ƒ”‡†–‘‘‹–‡”ˆ‡”‡– ‘–”‘Ž•ǡ–Š‡
    •ƒ’Ž‡Ž‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›ǡ‡š‘ǦŽ‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›ǡƒ†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ ‡‡–’”‡Ǧ
    †‡ˆ‹‡†ƒ ‡’–ƒ ‡–Š”‡•Š‘Ž†•Ǥ
    ƒ’Ž‡Ž‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›™ƒ•†‡–‡”‹‡†„›–Š‡†‡’–Š‘ˆ‘Ǧ•‹‰Ž‡–‘‘Ž‡ —Ž‡ȋȌ
    ‘˜‡”ƒ‰‡ƒ ”‘••–Š‡’ƒ‡ŽǤ‡†‹ƒ‘Ǧ•‹‰Ž‡–‘‘Ž‡ —Ž‡ ‘˜‡”ƒ‰‡ƒ ”‘••–ƒ”‰‡–‡†”‡‰‹‘•™ƒ•
    ‡˜ƒŽ—ƒ–‡†–‘†‡‘•–”ƒ–‡–Šƒ–‹ ”‘„‹ƒŽ‘”‹–‡”ˆ‡”‹‰•—„•–ƒ ‡•†‘‘–‹’ƒ –ƒ••ƒ›’‡”ˆ‘”ƒ ‡
    –‘•‡“—‡ ‡—‹“—‡‘Ž‡ —Ž‡•Ǥ‡ ‘˜‡”›‘ˆ—‹“—‡‘Ž‡ —Ž‡•ƒ ”‘••‹–‡”ˆ‡”‹‰•—„•–ƒ ‡ ‘†‹–‹‘•
    †‹†‘–•Š‘™ƒ‡‰ƒ–‹˜‡‹’ƒ –‘ˆ‹–‡”ˆ‡”‹‰•—„•–ƒ ‡•ȋˆ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹•’‹‡
    ‘†‹–‹‘‘˜‡””‡ˆ‡”‡ ‡ ‘†‹–‹‘”ƒ‰‡†ˆ”‘ͲǤͺͺ–‘ͳǤͲͺȌǤ
    ‡Žƒ–‹˜‡‡š‘ ‘˜‡”ƒ‰‡ ƒŽ —Žƒ–‡†ƒ•–Š‡”ƒ–‹‘‘ˆ‡†‹ƒ‡š‘ ‘˜‡”ƒ‰‡–‘•ƒ’Ž‡Ž‡˜‡Ž ‘˜‡”ƒ‰‡ˆ‘”
    ‡ƒ Š‘ˆ–Š‡ͷͲͺ‡š‘”‡‰‹‘•™ƒ• ‘’ƒ”‡†ˆ‘”‡ƒ Š ‘†‹–‹‘Ǧ”‡ˆ‡”‡ ‡•ƒ’Ž‡’ƒ‹”Ǥ‰‰”‡‰ƒ–‹‰
    ͳͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ƒ ”‘••ƒŽŽ•ƒ’Ž‡• ‘–”‹„—–‹‰–‘–Š‡ƒƒŽ›•‹•ǡ–Š‡–‘–ƒŽˆ”ƒ –‹‘‘ˆƒŽŽ‡š‘‹ ”‡‰‹‘•™‹–Š‹‡š’‡ –‡†
    Ž‡˜‡Ž‘ˆ†‹ˆˆ‡”‡ ‡•†‡ˆ‹‡†ƒ•ʹȗɐǡ™Š‡”‡ɐ‹•–Š‡’‘‘Ž‡†•–ƒ†ƒ”††‡˜‹ƒ–‹‘‘ˆ–Š‡†‹ˆˆ‡”‡ ‡•
    ‘„•‡”˜‡†‹Š‹•–‘”‹ ƒŽȋɐαͲǤͳͲͺȌ™‡”‡ ƒŽ —Žƒ–‡†Ǥ†‡”‘”ƒŽ†‹•–”‹„—–‹‘ƒ••—’–‹‘ǡ–Š‡ˆ”ƒ –‹‘
    ‘ˆ•— Š”‡‰‹‘•‹•‡š’‡ –‡†–‘„‡ͻͷΨǤŠ‡ˆ”ƒ –‹‘‘ˆ‡š‘•™‹–Š”‡Žƒ–‹˜‡‡š‘Ž‡˜‡Ž ‘˜‡”ƒ‰‡
    †‹ˆˆ‡”‡ ‡„‡–™‡‡ ‘†‹–‹‘ƒ†”‡ˆ‡”‡ ‡™‹–Š‹ʹɐȋʹȗͲǤͳͲͺȌ™ƒ•ͻͶǤ͵ǦͻͻǤ͹Ψǡ™Š‹ Š
    †‡‘•–”ƒ–‡•–Šƒ––Š‡”‡™ƒ•‘’”‡ˆ‡”‡–‹ƒŽ†”‘’Ǧ‘—–‘ˆ”‡Žƒ–‹˜‡‡š‘ǦŽ‡˜‡Ž ‘˜‡”ƒ‰‡‡š ‡‡†‹‰
    ‡š’‡ –‡†Ž‡˜‡Ž•†—‡–‘”ƒ†‘˜ƒ”‹ƒ–‹‘ǡƒ†–Š‡‡–‹”‡’ƒ‡Ž™ƒ• ‘˜‡”‡† ‘•‹•–‡–Ž›„‡–™‡‡
    ”‡ˆ‡”‡ ‡ƒ†‹–‡”ˆ‡”‹‰•—„•–ƒ ‡ ‘†‹–‹‘•Ǥ
    Š‡”‡•—Ž–•™‡”‡ƒ‰‰”‡‰ƒ–‡†ƒ ”‘••ƒŽŽ˜ƒ”‹ƒ–•ƒ ”‘••ƒŽŽ–‡™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡•ǡƒ† ‘ ‘”†ƒ ‡
    ™ƒ•ƒ••‡••‡†™‹–Š‹‡ƒ Š–”‡ƒ–‡– ƒ–‡‰‘”›ƒ ”‘••˜ƒ”‹ƒ–•Ǥ•™‡”‡ ƒŽ —Žƒ–‡†ˆ‘”͸ʹ•ǡʹͶ
    ‹†‡Ž•ǡƒ†͵•ǤŠ‡͸ ‘†‹–‹‘•–‡•–‡†•Š‘™‡†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ–•”ƒ‰‹‰ˆ”‘ͺ͵Ǥ͵ΨǦ
    ͳͲͲǤͲΨǤηͳš‘”ƒ‰‡†ˆ”‘ͻͲǤͲΨǦͳͲͲǤͲΨˆ‘”ƒŽŽ͸‹–‡”ˆ‡”‡–•Ǥ
    Š‡’ƒ‡ŽǦ™‹†‡•™‡”‡ƒŽ•‘ ƒŽ —Žƒ–‡†ˆ‘”•ƒ†‹†‡Ž•™‹–Š‹–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡ǤŠ‡
    †‹• ‘”†ƒ–‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•™‡”‡†‡ˆ‹‡†ƒ•–Š‘•‡‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•–Šƒ–™‡”‡’‘•‹–‹˜‡‹–Š‡‘Ǧ
    ”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǤŠ‡’ƒ‡ŽǦ™‹†‡™ƒ•ͻͻǤͻΨǦͳͲͲǤͲΨˆ‘”ƒŽŽ ‘†‹–‹‘•Ǥ
    ††‹–‹‘ƒŽŽ›ǡ–‘‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ‡š‘‰‡‘—•‹–‡”ˆ‡”‹‰•—„•–ƒ ‡•‘–Š‡’‡”ˆ‘”ƒ ‡
    ‘ˆ —ƒ”†ƒ–͵͸Ͳšǡ–‡†‹ˆˆ‡”‡–”‡’”‡•‡–ƒ–‹˜‡˜ƒ”‹ƒ–•™‡”‡–‡•–‡†—•‹‰ Ž‹‹ ƒŽ‘” ‡ŽŽŽ‹‡Ǧ
    †‡”‹˜‡† ˆ•ƒ’Ž‡••’‹‡†™‹–Š™ƒ•Š„—ˆˆ‡”ȋͳͲΨ˜Ȁ˜Ȍ ‘’ƒ”‡†–‘ƒ”‡ˆ‡”‡ ‡ ‘†‹–‹‘Ǥ ”‘••
    ƒ–‘–ƒŽ‘ˆʹͷ”‡ˆ‡”‡ ‡ƒ†–‡•–•ƒ’Ž‡•’ƒ••‹‰’‘•–Ǧ•‡“—‡ ‹‰ǡ–Š‡“—ƒŽ‹–ƒ–‹˜‡†‡–‡ –‹‘”ƒ–‡
    ”ƒ‰‡†„‡–™‡‡ͻͺǤ͵Ψƒ†ͳͲͲΨǢ’‡”Ǧ•ƒ’Ž‡ˆ‘”„‘–Š ‘†‹–‹‘•™‡”‡ͳͲͲΨǤ
     ‘ Ž—•‹‘ǡ‘‹–‡”ˆ‡”‡ ‡™ƒ•ˆ‘—†‹ƒŽ„—‹ȋ͸Ͳ‰ȀȌǡ ‘Œ—‰ƒ–‡†„‹Ž‹”—„‹ȋ͵ͶʹɊ‘ŽȀȌǡ
    — ‘Œ—‰ƒ–‡†„‹Ž‹”—„‹ȋ͵ͶʹɊ‘ŽȀȌǡŠ‡‘‰Ž‘„‹ȋʹ‰ȀȌǡStaphylococcus epidermidisȋͳͲ͸ ˆ— ǡ
    ‡š–”ƒ –‹‘™ƒ•Š„—ˆˆ‡”ȋͳͲΨ˜Ȁ˜Ȍ‘”–”‹‰Ž› ‡”‹†‡•ȋͳͷ‰ȀȌǤ

    b. •‹Ž‹ ‘ Analysis
    ”‹‡”ƒ†’”‘„‡•’‡ ‹ˆ‹ ‹–›™‡”‡ƒ††”‡••‡†„›ƒ’’‹‰’ƒ‡Ž’”‘„‡•–‘–Š‡Š—ƒ‰‡‘‡ǤŠ‡
    ƒ’’‡†–‘–Š‡Š—ƒ‰‡‘‡ȋŠ‰ͳͻȌ™‹–Š†‡ ‘›•‡“—‡ ‡•ǡ—’Žƒ ‡† ‘–‹‰•ǡƒ†”‡’”‡•‡–ƒ–‹˜‡
    ‹ ”‘„‹ƒŽ ‘–ƒ‹ƒ–•‰‡‘‡•ǡͻ͹Ǥ͸Ψ‘ˆ’”‘„‡•—‹“—‡Ž›ƒ’–‘–Š‡‰‡‘‡ȋη͸ͲȌǤ‘‡‘ˆ
    –Š‡’”‹‡”•‘”’”‘„‡•ƒ’’‡†–‘–Š‡”‡’”‡•‡–ƒ–‹˜‡‹ ”‘„‹ƒŽ ‘–ƒ‹ƒ–‰‡‘‡•Ǥ

    ͸ǤͷǤ ”‡ ‹•‹‘


    Š‡’—”’‘•‡‘ˆ–Š‡’”‡ ‹•‹‘•–—†‹‡•™ƒ•–‘†‡‘•–”ƒ–‡–Š‡”‡’‡ƒ–ƒ„‹Ž‹–›ƒ†™‹–Š‹Ǧ•‹–‡
    ”‡’”‘†— ‹„‹Ž‹–›‘ˆ —ƒ”†ƒ–͵͸Ͳš–Š”‘—‰Š Ž‘•‡‡••‘ˆƒ‰”‡‡‡–„‡–™‡‡‡ƒ•—”‡†“—ƒŽ‹–ƒ–‹˜‡
    ‘—–’—–‘„–ƒ‹‡†‹”‡’Ž‹ ƒ–‡–‡•–‹‰—•‹‰†‹ˆˆ‡”‡– ‘„‹ƒ–‹‘•‘ˆ”‡ƒ‰‡–Ž‘–•ǡ‹•–”—‡–•ǡ
    ‘’‡”ƒ–‘”•ǡƒ††ƒ›•Ǥ††‹–‹‘ƒŽ”—•™‡”‡ ‘†— –‡† ͳ Ȍ‘—–ƒ–‹‘Ǧ‡‰ƒ–‹˜‡•ƒ’Ž‡•–‘
    †‡‘•–”ƒ–‡’”‡ ‹•‹‘‘ˆƒƒŽ›–‹ ƒŽŽ›„Žƒ•ƒ’Ž‡•ƒ†ȋʹȌ‘’Žƒ•ƒ•ƒ’Ž‡•–‘—†‡”•–ƒ†–Š‡
    ‹ˆŽ—‡ ‡‘ˆ‡š–”ƒ –‹‘‘’”‡ ‹•‹‘ǤŽŽ•–—†‹‡•™‡”‡ ‘†— –‡†‡š Ž—•‹˜‡Ž›™‹–Š’ƒ–‹‡–Ǧ†‡”‹˜‡†
    •ƒ’Ž‡•Ǣ‘ ‡ŽŽŽ‹‡ƒ–‡”‹ƒŽ™ƒ•—•‡†Ǥ

    a. Precision Across Three Distinct cfDNA Clinical Sample Pools


    ”‡ ‹•‹‘™ƒ•‡˜ƒŽ—ƒ–‡†ˆ‘”ƒŽ–‡”ƒ–‹‘•ƒ••‘ ‹ƒ–‡†™‹–Šš Žƒ‹•ǡƒ•™‡ŽŽƒ•”‡’”‡•‡–ƒ–‹˜‡ƒ†
    •’‡ ‹ˆ‹ ƒŽ–‡”ƒ–‹‘•–‘•—’’‘”–’Žƒ–ˆ‘”ǦŽ‡˜‡Ž’‡”ˆ‘”ƒ ‡Ǥ‡’‡ƒ–ƒ„‹Ž‹–›‹ Ž—†‹‰‹–”ƒǦ”—
    ’‡”ˆ‘”ƒ ‡ȋ”—‘–Š‡•ƒ‡’Žƒ–‡—†‡”–Š‡•ƒ‡ ‘†‹–‹‘•Ȍƒ†”‡’”‘†— ‹„‹Ž‹–›‹ Ž—†‹‰‹–‡”Ǧ
    ”—’‡”ˆ‘”ƒ ‡ȋ”—‘†‹ˆˆ‡”‡–’Žƒ–‡•—†‡”†‹ˆˆ‡”‡– ‘†‹–‹‘•Ȍ™‡”‡ƒ••‡••‡†ƒ† ‘’ƒ”‡†
    ƒ ”‘••–Š”‡‡†‹ˆˆ‡”‡–’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•‘ˆ‹•–”—‡–•‡–•ǡ”‡ƒ‰‡–Ž‘–•ǡƒ†‘’‡”ƒ–‘”•‘˜‡”
    ͳ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    —Ž–‹’Ž‡†ƒ›•ǤŠ‹••–—†›™ƒ• ƒ””‹‡†‘—–‘–Š”‡‡†‹•–‹ – Ž‹‹ ƒŽ•ƒ’Ž‡’‘‘Ž•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”
    –›’‡•ǡ ‘–ƒ‹‹‰ƒ–‘–ƒŽ‘ˆͳ͸–ƒ”‰‡–‡†ƒŽ–‡”ƒ–‹‘•ƒ ”‘••–Š‡’‘‘Ž•ǡ’”‡’ƒ”‡†–ƒ”‰‡–‹‰ͳǦͳǤͷš‘ƒ–ͷ
    ‰ ˆ‹’—–ǡ‹ Ž—†‡†˜ƒ”‹ƒ–•ƒ••‘ ‹ƒ–‡†™‹–Šš Žƒ‹•ƒ†ƒ††‹–‹‘ƒŽ˜ƒ”‹ƒ–•‹–‡†‡†–‘
    †‡‘•–”ƒ–‡’ƒ‡ŽǦ™‹†‡˜ƒŽ‹†ƒ–‹‘Ǥ‡ȋͳͲȌ”‡’Ž‹ ƒ–‡•’‡”–Š”‡‡ȋ͵Ȍ’‘‘Ž•™‡”‡–‡•–‡†ˆ‘”‡ƒ Š‘ˆ
    –Š”‡‡ȋ͵Ȍ’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ȋͻͲ”‡’Ž‹ ƒ–‡•ƒ’Ž‡•–‘–ƒŽȌƒ† ‘’”‹•‡†‘ˆ–Š”‡‡ ͵Ȍ †‹ˆˆ‡”‡–
    ”‡ƒ‰‡–Ž‘–•ȋ —ƒ”†ƒ–͵͸Ͳǡ—”‡„‡ƒ†•ǡƒ†‡š–‡“ͷͷͲ•‡“—‡ ‹‰”‡ƒ‰‡–Ž‘–•Ȍǡ–Š”‡‡
    ȋ͵Ȍ†‹ˆˆ‡”‡–‹•–”—‡–•‡–•ƒ†–Š”‡‡ȋ͵Ȍ†‹ˆˆ‡”‡–‘’‡”ƒ–‘”‰”‘—’•Ǥƒ Š ‘„‹ƒ–‹‘™ƒ•–‡•–‡†‘
    –™‘ȋʹȌ„ƒ– Š‡•ǡ•‡“—‡ ‡†‘ˆ‘—”ȋͶȌˆŽ‘™ ‡ŽŽ•ǤŠ‡ •›’Š‘›‹•–”—‡–™ƒ•‘–’ƒ‹”‡†
    ™‹–Š‹‡ƒ Š‘ˆ–Š‡–Š”‡‡ȋ͵Ȍ’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•‡–•ǡ•‹ ‡–Š‡•ƒ’Ž‡’‘‘Ž•™‡”‡‰‡‡”ƒ–‡†ˆ”‘
    ’”‡˜‹‘—•Ž›‡š–”ƒ –‡†ƒ†•–‘”‡† ˆǤ”‡ ‹•‹‘•–ƒ”–‹‰ˆ”‘ ˆ‡š–”ƒ –‹‘™ƒ•‡˜ƒŽ—ƒ–‡†‹ƒ
    •‡’ƒ”ƒ–‡•–—†›†‡• ”‹„‡†‹Section 6.5.f Precision from Plasma Evaluation of Extraction
    Precision and Precision of Downstream Steps. –‘–ƒŽǡͶͺͲƒŽ–‡”ƒ–‹‘•™‡”‡ƒ••‡••‡†ƒ ”‘••ͻͲ
    •ƒ’Ž‡•–‡•–‡†Ǥ—ƒŽ‹–ƒ–‹˜‡”‡•—Ž–•™‡”‡—•‡†–‘ ƒŽ —Žƒ–‡ƒ†Ǥ
    Š‡ˆ‹ƒŽŽ‡˜‡Ž•ˆ‘”–Š‡–ƒ”‰‡–‡†˜ƒ”‹ƒ–•–‡•–‡†”ƒ‰‡†ˆ”‘ͲǤ͹š–‘ʹǤ͸š‘ǤŠ”‡‡˜ƒ”‹ƒ–•™‡”‡
    „‡Ž‘™ͳš‘ȋROS1ˆ—•‹‘ƒ–ͲǤͻš‘ǡMETƒ’Ž‹ˆ‹ ƒ–‹‘ƒ–ͲǤͺš‘ǡƒ†NRAS͸ͳƒ–ͲǤ͹š‘Ȍǡͺ
    ™‡”‡™‹–Š‹ͳǦͳǤͷš”ƒ‰‡ǡ‹ Ž—†‹‰–Š‡š˜ƒ”‹ƒ–•ǡƒ†ͷ˜ƒ”‹ƒ–•™‡”‡‹–Š‡ͳǤ͹šȂʹǤ͸š‘
    ”ƒ‰‡Ǥ
     ”‘••ͻ͸Ͳ‡š’‡ –‡†‡‰ƒ–‹˜‡–ƒ”‰‡–‡†•‹–‡•ȋ͵ʹ–ƒ”‰‡–‡†‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•ƒ ”‘••͵•ƒ’Ž‡’‘‘Ž•ȗ͵Ͳ
    ”‡’Ž‹ ƒ–‡•Ȍǡ–Š‡‘„•‡”˜‡†™ƒ•ͳͲͲǤͲΨǤŽŽšƒŽ–‡”ƒ–‹‘•†‡‘•–”ƒ–‡†ƒ ‡’–ƒ„Ž‡’”‡ ‹•‹‘
    ȋͻ͸Ǥ͹ΨǦͳͲͲǤͲΨȌǡTable 14Ǥ
    Š‡˜ƒ”‹ƒ–Ž‡˜‡Žˆ‘”ƒŽŽ–ƒ”‰‡–‡†˜ƒ”‹ƒ–•™‡”‡ƒ„‘˜‡ͻͲǤͲΨƒ ”‘••ƒŽŽ‹•–”—‡–ǡ”‡ƒ‰‡–ǡƒ†
    ‘’‡”ƒ–‘” ‘„‹ƒ–‹‘•ǡ‡š ‡’–ˆ‘”METƒ’Ž‹ˆ‹ ƒ–‹‘‹’‘‘Žͳǡ™Š‹ Šƒ›„‡ƒ––”‹„—–‡†–‘–Š‡ͲǤͺš
    ‘”ƒ‰‡ƒ Š‹‡˜‡†‹–Š‡–‹–”ƒ–‹‘’‘‘ŽȋTable 14 Ǥ ROS1ˆ—•‹‘†‡–‡ –‹‘†‡‘•–”ƒ–‡†ͻ͵Ǥ͵Ψǡ
    ‘•‹•–‡–™‹–Š–Š‡ƒ Š‹‡˜‡†ͲǤͻš‘–‹–”ƒ–‹‘Ž‡˜‡ŽǤBRCA1ʹ͵ˆ•ƒŽ•‘”‡•—Ž–‡†‹ƒŽ‘™‡”˜ƒ”‹ƒ–
    Ž‡˜‡ŽȋͻͲǤͲΨȌ–Šƒ‡š’‡ –‡†Ǥ ‘™‡˜‡”ǡ–Š‡ͻͲǤͲΨ†‡–‡ –‹‘”ƒ–‡‹• ‘•‹•–‡–™‹–Š–Š‡˜ƒ”‹ƒ–
    „‡‹‰Ž‘ ƒ–‡†‹ƒ‘”‡ ŠƒŽŽ‡‰‹‰ƒ”‡ƒ‘ˆ–Š‡’ƒ‡Ž™‹–Š”‡•’‡ ––‘ ‘˜‡”ƒ‰‡Ǥ’‡ ‹ˆ‹ ƒŽŽ›ǡ–Š‡˜ƒ”‹ƒ–
    ‹• ‘•‹†‡”‡†–‘„‡‹ƒ‘”‡ ŠƒŽŽ‡‰‹‰ƒ”‡ƒ„‡ ƒ—•‡‹–‹•‹ƒ”‡‰‹‘™‹–Š”‡Žƒ–‹˜‡Ž›Ž‘™  ‘–‡–
    ƒ†Šƒ•„‡Ž‘™ƒ˜‡”ƒ‰‡‘Ž‡ —Ž‡”‡ ‘˜‡”›Ǥ
     ”‘••ͶͺͲƒŽ–‡”ƒ–‹‘•ȋͳͷͲ•ǡͳͷͲ‹†‡Ž•ǡ͸Ͳ•ǡƒ†ͳʹͲˆ—•‹‘•Ȍǡˆ”‘ƒ•‡–‘ˆͻͲ ˆ
    •ƒ’Ž‡”‡’Ž‹ ƒ–‡• ‘–ƒ‹‹‰ͳ͸—‹“—‡ƒŽ–‡”ƒ–‹‘•ƒ ”‘••͵ ˆ•ƒ’Ž‡’‘‘Ž•ƒ†‡ˆ”‘ ˆ
    ˆ”‘—Ž–‹’Ž‡ ƒ ‡”–›’‡•ǡƒŽŽƒŽ–‡”ƒ–‹‘•†‡‘•–”ƒ–‡†‘ˆͺ͸Ǥ͹ΨǦͳͲͲǤͲΨǤŽ–‡”ƒ–‹‘ǦŽ‡˜‡Ž
    ”‡’‡ƒ–ƒ„‹Ž‹–›ƒ†”‡’”‘†— ‹„‹Ž‹–›•Š‘™‡†Š‹‰Š‘˜‡”ƒŽŽ’‘•‹–‹˜‡ ƒŽŽ”ƒ–‡•ȋ Table 14 Ǥ

    Table 14. Summary of Precision PPA Results


    Number Positive /
    Alteration Class Alteration Number Expected PPA (95% CI)
     EGFR͹ͻͲ ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǡͳͲͲǤͲΨȌ
     EGFRͺͷͺ ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǡͳͲͲǤͲΨȌ
    †‡Ž EGFRš‘ͳͻ‡Žǡ ʹͻȀ͵Ͳ ͻ͸Ǥ͹ΨȋͺʹǤͺΨǡͻͻǤͻΨȌ
    ͹Ͷ͸̴͹ͷͲ†‡Ž
     KRAS ͳʹ ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǡͳͲͲǤͲΨȌ
     NRAS͸ͳ ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǡͳͲͲǤͲΨȌ
     BRAF͸ͲͲ ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǡͳͲͲǤͲΨȌ
    †‡Ž ERBB2͹͹ͷ̴ ͹͹͸‹• ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǡͳͲͲǤͲΨȌ
    †‡Ž EGFR͹͸͹̴͹͸ͻ†—’ ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǦͳͲͲǤͲΨȌ
    †‡Ž BRCA1ʹ͵ˆ• ʹ͹Ȁ͵Ͳ ͻͲǤͲΨȋ͹͵ǤͷΨǦͻ͹ǤͻΨȌ
    †‡Ž BRCA2ͳͻͺʹˆ• ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǦͳͲͲǤͲΨȌ
    ͳ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Number Positive /
    Alteration Class Alteration Number Expected PPA (95% CI)
     ERBB2 ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǦͳͲͲǤͲΨȌ
     MET ʹ͸Ȁ͵Ͳ ͺ͸Ǥ͹Ψȋ͸ͻǤ͵ΨǦͻ͸ǤʹΨȌ
    —•‹‘ ͶǦALK ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǦͳͲͲǤͲΨȌ
    —•‹‘ ͵ǦNTRK1 ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǦͳͲͲǤͲΨȌ
    —•‹‘  ͵͵ǦRET ͵ͲȀ͵Ͳ ͳͲͲǤͲΨȋͺͺǤͶΨǦͳͲͲǤͲΨȌ
    —•‹‘ ROS1Ǧ͸ ʹͺȀ͵Ͳ ͻ͵Ǥ͵Ψȋ͹͹ǤͻΨǦͻͻǤʹΨȌ
     ƒ‡ŽǦ™‹†‡ ͳͷͲȀͳͷͲ ͳͲͲǤͲΨȋͻ͹Ǥ͸ΨǦͳͲͲǤͲΨȌ
    †‡Ž ƒ‡ŽǦ™‹†‡ ͳͶ͸ȀͳͷͲ ͻ͹Ǥ͵Ψȋͻ͵Ǥ͵ΨǦͻͻǤ͵ΨȌ

    Š‡ƒ ”‘••ƒŽŽ–ƒ”‰‡–‡†ƒŽ–‡”ƒ–‹‘•ˆ‘”‡ƒ Š ‘†‹–‹‘™ƒ•‡˜ƒŽ—ƒ–‡†ǤŠ‡ƒ ”‘••ƒŽŽ–ƒ”‰‡–‡†


    ƒŽ–‡”ƒ–‹‘•’‡”’”‡ ‹•‹‘ ‘„‹ƒ–‹‘ȋȌ”ƒ‰‡†ˆ”‘ͻ͸Ǥ͵ΨǦͻͻǤͶΨǤ
    ”‡ ‹•‹‘ˆ”‘ Ž‹‹ ƒŽ’‘‘Ž•™‹–Š•ƒ’Ž‡•ˆ”‘ƒ•‹‰Ž‡ Ž‹‹ ƒŽŽ›”‡Ž‡˜ƒ– ƒ ‡”–›’‡™ƒ• ‘ˆ‹”‡†
    ‹–Š‡ ‘„‹‡†‘ ‘ˆ‹”ƒ–‹‘ƒ†’”‡ ‹•‹‘•–—†›†‡• ”‹„‡†‹Section 6.3.b Limit of Detection
    (LoD)Ǥ

    b. Precision for   exon 20 Insertions from NSCLC cfDNA Clinical Sample Pools
    •‡’ƒ”ƒ–‡’”‡ ‹•‹‘•–—†›‡˜ƒŽ—ƒ–‡†–Š”‡‡EGFR‡š‘ʹͲ‹•‡”–‹‘•—•‹‰ Ž‹‹ ƒŽ•ƒ’Ž‡
    ’‘‘Ž•Ǥ”‡ ‹•‹‘™ƒ•ƒ••‡••‡†ƒ† ‘’ƒ”‡†ƒ ”‘•••‹š†‹ˆˆ‡”‡–—‹“—‡”‡ƒ‰‡–Ž‘–ǡ‹•–”—‡–ǡƒ†
    ‘’‡”ƒ–‘” ‘„‹ƒ–‹‘•‘˜‡”†‹ˆˆ‡”‡–•–ƒ”–†ƒ–‡•Ǥ
    ƒ”‹ƒ–•‘—” ‡’‘‘Ž•™‡”‡’”‡’ƒ”‡†„›†‹Ž—–‹‰’ƒ–‹‡– ˆ•ƒ’Ž‡•’‘•‹–‹˜‡ˆ‘”•‡Ž‡ –‡†
    EGFR‡š‘ʹͲ‹•‡”–‹‘•™‹–Š—–ƒ–‹‘Ǧ‡‰ƒ–‹˜‡ ˆ†‡”‹˜‡†ˆ”‘ Ž‹‹ ƒŽ•ƒ’Ž‡•Ǥƒ Š
    ‹•‡”–‹‘™ƒ•–‡•–‡†ƒ ”‘•••‹š’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ƒ–ͷ‰‹’—–ƒ– Ž‡˜‡Ž•”ƒ‰‹‰ˆ”‘ͳǤͲš
    –‘ͳǤͳš‘Ǥ
    ”ƒ‰‡†ˆ”‘ͻ͹Ǥ͸Ψ–‘ͳͲͲΨƒ ”‘•••’‡ ‹ˆ‹ ‹•‡”–‹‘•ƒ†™ƒ•ͻͺǤͶΨƒ ”‘••ƒŽŽ‹•‡”–‹‘•ƒ†
    ’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ȋTable 15 Ǥ

    Table 15. Summary of Precision PPA Results for EGFR Exon 20 Insertions
    Alteration Number Positive / Number Expected PPA (95% CI)
    EGFR‡š‘ʹͲ‹•‡”–‹‘• ͳʹ͵Ȁͳʹͷ ͻͺǤͶΨȋͻͶǤ͵ΨǡͻͻǤͺΨȌ

    c. Precision for ERBB2 Activating Mutations (SNVs and Exon 20 Insertions) from NSCLC cfDNA Clinical
    Sample Pools
    ’”‡ ‹•‹‘•–—†›‡˜ƒŽ—ƒ–‡†ˆ‹˜‡ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ—•‹‰
     Ž‹‹ ƒŽ•ƒ’Ž‡’‘‘Ž•Ǥ”‡ ‹•‹‘™ƒ•ƒ••‡••‡†ƒ† ‘’ƒ”‡†ƒ ”‘•••‹š†‹ˆˆ‡”‡–—‹“—‡
    ”‡ƒ‰‡–Ž‘–ǡ‹•–”—‡–ǡƒ†‘’‡”ƒ–‘” ‘„‹ƒ–‹‘•‘˜‡”†‹ˆˆ‡”‡–•–ƒ”–†ƒ–‡•Ǥ
    ƒ”‹ƒ–•‘—” ‡’‘‘Ž•™‡”‡’”‡’ƒ”‡†„›†‹Ž—–‹‰’ƒ–‹‡– ˆ•ƒ’Ž‡•’‘•‹–‹˜‡ˆ‘”•‡Ž‡ –‡†
    ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ™‹–Š—–ƒ–‹‘Ǧ‡‰ƒ–‹˜‡ ˆ†‡”‹˜‡†
    ˆ”‘ Ž‹‹ ƒŽ•ƒ’Ž‡•Ǥƒ Š˜ƒ”‹ƒ–™ƒ•–‡•–‡†ƒ ”‘•••‹š’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ƒ–ͷ‰‹’—–
    ƒ– Ž‡˜‡Ž•”ƒ‰‹‰ˆ”‘ͳǤͲš–‘ͳǤͶš‘Ǥ
    ”ƒ‰‡†ˆ”‘ͻͷǤ͹Ψ–‘ͳͲͲΨƒ ”‘•••’‡ ‹ˆ‹ ˜ƒ”‹ƒ–•ƒ†™ƒ•ͻͻǤʹΨƒ ”‘••ƒŽŽ˜ƒ”‹ƒ–•ƒ†
    ’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ȋTable 16 Ǥ

    ͳͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 16. Summary of Precision PPA Results for ERBB2 Activating Mutations (SNVs and Exon
    20 Insertions)
    Alteration Number Positive / Number Expected PPA (95% CI)
    ERBB2• ͹ͲȀ͹ͳ ͻͺǤ͸ΨȋͻʹǤͶΨǡͳͲͲǤͲΨȌ
    ERBB2‡š‘ʹͲ‹•‡”–‹‘• Ͷ͹ȀͶ͹ ͳͲͲΨȋͻʹǤͷΨǡͳͲͲǤͲΨȌ

    d. Precision for  G12C from NSCLC cfDNA Clinical Sample Pools
    Š‡’—”’‘•‡‘ˆ–Š‡’”‡ ‹•‹‘•–—†›™ƒ•–‘†‡‘•–”ƒ–‡–Š‡”‡’‡ƒ–ƒ„‹Ž‹–›ƒ†™‹–Š‹Ǧ•‹–‡
    ”‡’”‘†— ‹„‹Ž‹–›‘ˆ —ƒ”†ƒ–͵͸Ͳšˆ‘”†‡–‡ –‹‰KRAS ͳʹ—–ƒ–‹‘–Š”‘—‰Š Ž‘•‡‡••‘ˆ
    ƒ‰”‡‡‡–„‡–™‡‡“—ƒŽ‹–ƒ–‹˜‡†‡–‡ –‹‘‹”‡’Ž‹ ƒ–‡•—•‹‰†‹ˆˆ‡”‡– ‘„‹ƒ–‹‘•‘ˆ”‡ƒ‰‡–Ž‘–•ǡ
    ‹•–”—‡–•ǡ‘’‡”ƒ–‘”•ǡƒ††ƒ›•ǤŠ‡•–—†›™ƒ• ‘†— –‡†™‹–Š’‘‘Ž‡†’ƒ–‹‡–•ƒ’Ž‡•
    Šƒ”„‘”‹‰KRAS ͳʹ—–ƒ–‹‘•Ǥ
    ™‘ ˆ•ƒ’Ž‡’‘‘Ž•Šƒ”„‘”‹‰KRAS ͳʹ™‡”‡’”‡’ƒ”‡†ƒ––ƒ”‰‡–‡† Ž‡˜‡Ž•‘ˆͳǦͳǤͷš‘
    ƒ†–‡•–‡†ƒ––Š‡ͷ‰ȋʹǤͶΨ ǡͳǤ͵š‘Ȍƒ†͵Ͳ‰ȋͲǤ͹Ψ ǡͳǤͶš‘Ȍ ˆ‹’—–ƒ‘—–•Ǥ
    ‘”–Š‡ͷ‰ƒ†͵Ͳ‰‹’—–ƒ‘—–•ǡ•‡˜‡ȋ͹Ȍƒ†–Š”‡‡ȋ͵Ȍ”‡’Ž‹ ƒ–‡•™‡”‡–‡•–‡†ǡ”‡•’‡ –‹˜‡Ž›ǡˆ‘”
    ‡ƒ Š‘ˆ•‹šȋ͸Ȍ’”‡ ‹•‹‘ ‘„‹ƒ–‹‘• ‘’‘•‡†‘ˆ–Š”‡‡†‹ˆˆ‡”‡–”‡ƒ‰‡–Ž‘–•ǡ–™‘†‹ˆˆ‡”‡–
    ‹•–”—‡–•‡–•ǡƒ†–™‘†‹ˆˆ‡”‡–‘’‡”ƒ–‘”‰”‘—’•Ǥ –‘–ƒŽǡͶʹ”‡’Ž‹ ƒ–‡•™‡”‡–‡•–‡†ƒ––Š‡ͷ‰‹’—–
    Ž‡˜‡Žƒ†ͳͺ”‡’Ž‹ ƒ–‡•ƒ––Š‡͵Ͳ‰‹’—–Ž‡˜‡ŽǤ
    Š‹••–—†›•— ‡••ˆ—ŽŽ›˜‡”‹ˆ‹‡†–Š‡’”‡ ‹•‹‘‘ˆ —ƒ”†ƒ–͵͸Ͳšˆ‘”†‡–‡ –‹‰KRAS ͳʹ—–ƒ–‹‘
    ™‹–Š‹ƒ†„‡–™‡‡†‹ˆˆ‡”‡–”‡ƒ‰‡–Ž‘–•ǡ‹•–”—‡–•‡–•ǡƒ†‘’‡”ƒ–‘”‰”‘—’•™‹–Š•ƒ’Ž‡•‡ƒ”
    ‘’”‘ ‡••‡†‘†‹ˆˆ‡”‡–”—•ƒ††ƒ›•‹–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽƒ„‘”ƒ–‘”›ȋ Table 17 ǤŠ‡
    ƒ ‡’–ƒ ‡ ”‹–‡”‹ƒ™‡”‡‡–™‹–Šƒ’‘•‹–‹˜‡’”‡ ‹•‹‘‘ˆͳͲͲΨƒ–„‘–Šͷƒ†͵Ͳ‰ ˆ‹’—–•Ǥ

    Table 17. Summary of Precision Results for KRAS G12C


    Input Amount Concordant / Expected Positives PPA (95% CI)
    ͷ‰ ͶʹȀͶʹ ͳͲͲΨȋͻͳǤ͸ΨǦͳͲͲǤͲΨȌ
    ͵Ͳ‰ ͳͺȀͳͺ ͳͲͲΨȋͺͳǤͷΨǦͳͲͲǤͲΨȌ

    e. Precision for ESR1 mutations


    ”‡ ‹•‹‘‘ˆESR1—–ƒ–‹‘•‘ —ƒ”†ƒ–͵͸Ͳš™ƒ•ƒƒŽ›œ‡†ˆ‘”ESR1 ͵ͷ͸ǡ͵ͺͲǡ ͶͶʹǡ
    Ͷ͸͵ǡͷ͵͹ǡƒ†ͷ͵ͺ ƒ–ͷ‰ ˆ‹’—–—•‹‰„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•ƒ’Ž‡•Ǥƒ Š—–ƒ–‹‘
    ™ƒ•–‡•–‡†ƒ–ͳǦ͵‘ǡ™Š‹ Š™ƒ•‡•–ƒ„Ž‹•Š‡†ˆ‘”’”‡˜ƒŽ‡–ESR1—–ƒ–‹‘•ȋ͵ͺͲǡͷ͵͹ǡͷ͵ͺ ǡ
    ™‹–ŠʹͶ”‡’Ž‹ ƒ–‡•ƒ ”‘••͸—‹“—‡”‡ƒ‰‡–Ž‘–Ǧ‹•–”—‡–Ǧ‘’‡”ƒ–‘” ‘„‹ƒ–‹‘•ǡ™Š‹ Šƒ”‡–Š‡ƒ‹
    •‘—” ‡•‘ˆ˜ƒ”‹ƒ„‹Ž‹–›‹ƒƒ—–‘ƒ–‡†ƒ••ƒ›ȋTable 18 Ǥ

    Table 18. Summary of Precision Results for ESR1 Mutations


    ESR1 Missense Observed Number Positive/ PPA
    Relative LoD Level*
    Mutation MAF% Number Expected (95% CI)
    ͳͲͲΨ
    ͵ͺͲ ͳǤͲ ͳǤͲš ʹͶȀʹͶ
    ȋͺͷǤͺΨǦͳͲͲΨȌ
    ͻͷǤͺΨ
    ͷ͵͹ ͳǤͲ ͳǤͲš ʹ͵ȀʹͶ
    ȋ͹ͺǤͻΨǦͻͻǤͻΨ 
    ͻͷǤͺΨ
    ͷ͵ͺ  ͳǤͳ ͳǤͲš ʹ͵ȀʹͶ
    ȋ͹ͺǤͻΨǦͻͻǤͻΨ 
    ͺ͵Ǥ͵Ψ
    ͵ͷ͸ ʹǤͳȗȗ ʹǤͲš ʹͲȀʹͶ
    ȋ͸ʹǤ͸ΨǦͻͷǤ͵Ψ 
    ͻͳǤ͹Ψ
    ͵ͷ͸ ͵Ǥͳȗȗ ʹǤͻš ʹʹȀʹͶ
    ȋ͹͵ǤͲΨǦͻͻǤͲΨ 

    ͳͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ͳͲͲΨ
    ͶͶʹ ʹǤ͵ ʹǤͳš ʹͶȀʹͶ
    ȋͺͷǤͺΨǦͳͲͲΨȌ
    ͳͲͲΨ
    Ͷ͸͵ ʹǤͺ ʹǤ͸š ʹͶȀʹͶ
    ȋͺͷǤͺΨǦͳͲͲΨȌ
    ȗ‘’ƒ”‡†–‘–Š‡‡•–ƒ„Ž‹•Š‡†‘ˆ‘”–Š‡’”‡˜ƒŽ‡–ESR1‹••‡•‡—–ƒ–‹‘•Ǥ
    ȗȗ‘–‡–Šƒ––Š‡‘„•‡”˜‡† ‹•–Š‡ƒ˜‡”ƒ‰‡˜ƒ”‹ƒ– ˆ”‘ƒŽŽ•ƒ’Ž‡•™‹–Šƒ”‡’‘”–‡†˜ƒ”‹ƒ–ȋ‹Ǥ‡Ǥǡ‡š Ž—†‹‰
    †”‘’‘—–•ȌǤ

    f. Precision from Plasma Evaluation of Extraction Precision and Precision of Downstream Steps
    Š‡’—”’‘•‡‘ˆ–Š‹••–—†›™ƒ•–‘•Š‘™–Š‡’”‡ ‹•‹‘‘ˆ˜ƒ”‹ƒ– ƒŽŽ‹‰ˆ‘”–Š‡‡–‹”‡•ƒ’Ž‡™‘”ˆŽ‘™
    ȋˆ”‘ ˆ‡š–”ƒ –‹‘–Š”‘—‰Š•‡“—‡ ‹‰Ȍ™‹–Š—Ǧ’‘‘Ž‡† Ž‹‹ ƒŽ•ƒ’Ž‡•Ǥ
    Š‹••–—†›—–‹Ž‹œ‡† Ž‹‹ ƒŽ’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘ͷ͵—‹“—‡’ƒ–‹‡–•Ǥƒ Š’Žƒ•ƒ•ƒ’Ž‡™‹–Š’‘•‹–‹˜‡
    ˜ƒ”‹ƒ–•ȋƒ•†‡–‡ –‡†„› —ƒ”†ƒ–͵͸ͲȌƒ†Š‹‰Š ˆ›‹‡Ž†•™ƒ••’Ž‹–‹–‘•‹šƒŽ‹“—‘–•‘”•‹š
    ”‡’Ž‹ ƒ–‡•’‡”’ƒ–‹‡–Ǥ
    Š‡‘™ƒ•‡•–ƒ„Ž‹•Š‡†ˆ‘”‹’—–•‘ˆͷ‰ƒ†͵Ͳ‰ǡ™Š‹ Šƒ”‡–Š‡Ž‘™‡”ƒ†—’’‡”Ž‹‹–‘ˆ ˆ
    ƒ••‹’—–ˆ‘”Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘Ǥ‹ ‡–Š‡’—”’‘•‡‘ˆ–Š‹•’”‡ ‹•‹‘•–—†›™ƒ•–‘–‡•––Š‡ˆ—ŽŽ
    •’‡ –”—‘ˆ•ƒ’Ž‡›‹‡Ž†•–Šƒ–™‘—Ž†„‡‘„•‡”˜‡†‹‘”ƒŽ—•‡ǡ•ƒ’Ž‡‹’—–•”ƒ‰‡†ˆ”‘ͷ‰–‘
    ͵Ͳ‰‘ˆ ˆ‹’—–ǤŠ‡ ‘””‡•’‘†‹‰‘”ƒ‰‡™ƒ•„‡–™‡‡ͳš–Š‡͵Ͳ‰‘ •ǡƒ†ͳǤͷš–Š‡
    ͷ‰‘ •Ǥƒ”‹ƒ–•–Šƒ–™‡”‡’”‡˜‹‘—•Ž›‘„•‡”˜‡†‹–Š‹• ”ƒ‰‡‹–Š‡ —ƒ”†ƒ–͵͸Ͳ
    ”—™‡”‡•‡Ž‡ –‡†ˆ‘”–Š‹••–—†›ƒ†‡˜ƒŽ—ƒ–‡†ˆ‘” ƒŽŽƒ‰”‡‡‡–Ǥ
    ‹‰Š–‡‡ȋͳͺȌ†‹ˆˆ‡”‡––—‘”–›’‡•™‡”‡‡˜ƒŽ—ƒ–‡†‹–Š‹••–—†›–‘•—’’‘”–ƒ’ƒǦ ƒ ‡”–—‘”
    ’”‘ˆ‹Ž‹‰‹†‹ ƒ–‹‘ˆ‘” —ƒ”†ƒ–͵͸ͲšǤƒ Š†‘‘”•’‡ ‹‡™ƒ•’”‘ ‡••‡†‹†—’Ž‹ ƒ–‡ƒ ”‘••
    –Š”‡‡Ž‘–•ˆ‘”ƒ–‘–ƒŽ‘ˆ͸”‡’Ž‹ ƒ–‡•ǤDz‘–dz”‡ˆ‡”•–‘†‹ˆˆ‡”‡–”‡ƒ‰‡–Ž‘–•ǡƒ•™‡ŽŽƒ•†‹ˆˆ‡”‡–
    ‘„‹ƒ–‹‘•‘ˆ‘’‡”ƒ–‘”•ǡ†ƒ›•ǡƒ†‹•–”—‡–•–‘‡˜ƒŽ—ƒ–‡’”‡ ‹•‹‘ǤŠ‡–ƒ”‰‡–‡†˜ƒ”‹ƒ–•
    ‡˜ƒŽ—ƒ–‡†‹–Š‡•–—†›ƒ”‡•Š‘™‹Table 19Ǥ

    Table 19. Targeted Variants amongst the 53 Donor Samples Selected for Study
    Category Variant Number of Eligible Based on MAF/CN
    ERBB2  ͵
    MET  ͵
    ALK ˆ—•‹‘ ʹ
    RET ˆ—•‹‘ ʹ
    EGFR‡š‘ͳͻ†‡Ž‡–‹‘ ‹†‡Ž ͸
    EGFR‡š‘ʹͲ‹•‡”–‹‘ ‹†‡Ž ʹ
    ‘‰‹†‡Žȋε͵Ͳ„’Ȍ ‹†‡Ž ͳ
    MET‡š‘ͳͶ•‹’’‹‰ ‹†‡Ž ͳ
    BRAF͸ͲͲ  ͵
    EGFRͺͷͺ  ͸
    EGFR͹ͻͲ  Ͷ
    KRAS ͳʹ  ͵
    PIK3CAͷͶʹ  ͵
    PIK3CAͷͶͷ  Ͷ
    PIK3CA ͳͲͶ͹Ȁ  ʹ
    PIK3CAͶʹͲ  ͵

    –‘–ƒŽ‘ˆ͵ͳͷ”‡’Ž‹ ƒ–‡•’ƒ••‡†ƒ†™‡”‡ƒƒŽ›œ‡†ˆ‘”™‹–Š‹Ǧ ‘†‹–‹‘ƒ†„‡–™‡‡Ǧ ‘†‹–‹‘


    ’”‡ ‹•‹‘Ǥ

    ʹͲ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‘”‡ƒ Š‡Ž‹‰‹„Ž‡˜ƒ”‹ƒ–ǡ’ƒ‹”™‹•‡ ‘’ƒ”‹•‘•‘ˆ˜ƒ”‹ƒ–†‡–‡ –‹‘™‡”‡ƒ†‡„‡–™‡‡–Š‡–‡ Š‹ ƒŽ
    ”‡’Ž‹ ƒ–‡•‹‡ƒ ŠŽ‘–Ǥ ”‘–Š‡•–—†›†‡•‹‰™‹–Š–Š”‡‡Ž‘–•ƒ†–™‘”‡’Ž‹ ƒ–‡•™‹–Š‹‡ƒ ŠŽ‘–ǡ–Š‡”‡
    ™‡”‡͵’ƒ‹”•ˆ‘”‡ƒ Š˜ƒ”‹ƒ–‹ ƒŽ —Žƒ–‹‰™‹–Š‹ǦŽ‘–ƒ˜‡”ƒ‰‡’‘•‹–‹˜‡ƒ‰”‡‡‡–ȋȌƒ†ͳʹ’ƒ‹”•
    ˆ‘”‡ƒ Š˜ƒ”‹ƒ–‹ ƒŽ —Žƒ–‹‰„‡–™‡‡ǦŽ‘–Ǥ
    Š‡”‡•—Ž–•ˆ‘”‡Ž‹‰‹„Ž‡•ǡ‹†‡Ž•ǡˆ—•‹‘•ǡ•ƒ†ƒŽŽ–Š”‡‡–‘‰‡–Š‡”ƒ”‡•Š‘™‹Table 20Ǥ
    ‘”ˆŽ‘™‘”•ƒ’Ž‡ˆƒ‹Ž—”‡•‡ƒ–Š‡”‡™‡”‡ˆ‡™‡”–Šƒ͵Ž‘–•’‡”˜ƒ”‹ƒ––‡•–‡†‹•‘‡ ƒ•‡•Ǥ
    Š‡™‹–Š‹Ž‘–ˆ‘”ƒŽŽ˜ƒ”‹ƒ––›’‡•–‘‰‡–Š‡”™ƒ•ͻ͹Ǥ͵Ψƒ••Š‘™‹Table 20Ǥ

    Table 20. Within Reagent Lot APA Summary


    Variant Lot
    Variant Type Comparisons Concordant (C) Discordant (D) APA
     ͳͷͲ ͳͶͳ ͻ ͻ͸ǤͻΨ
    †‡Ž ͵ͷ ͵ͷ Ͳ ͳͲͲǤͲΨ
     ͳͷ ͳ͵ ʹ ͻʹǤͻΨ
    —•‹‘ ͳʹ ͳʹ Ͳ ͳͲͲǤͲΨ
     ʹͳʹ ʹͲͳ ͳͳ ͻ͹Ǥ͵Ψ

    Š‡™‹–Š‹ǦŽ‘–™ƒ•ͻͻǤͻΨǤŠ‹••–ƒ–‹•–‹ ‹ Ž—†‡•ƒŽŽ ƒŽŽ‡†˜ƒ”‹ƒ–•‹–‡•’ƒ‡ŽǦ™‹†‡ǡ‘–Œ—•––Š‡


    ‡Ž‹‰‹„Ž‡˜ƒ”‹ƒ–••‹–‡•„ƒ•‡†‘‘‹–Š‡•‘—” ‡•ƒ’Ž‡•ǡ•‘–Š‹••–ƒ–‹•–‹ ‹ Ž—†‡•’‘•‹–‹‘•™‹–Š
    ‡š’‡ –‡†•–‘ Šƒ•–‹ †‡–‡ –‹‘†—‡–‘Ž‘™—–ƒ–‘Ž‡ —Ž‡ ‘—–ǤŠ‡—„‡”‘ˆ’‘•‹–‹‘•‡˜ƒŽ—ƒ–‡†
    ™ƒ•Ͷ͸ǡʹͳ͹—‹“—‡ƒ†‹†‡Ž”‡’‘”–ƒ„Ž‡’‘•‹–‹‘•ǡʹ•ǡƒ†Ͷˆ—•‹‘•Ǥ
    Š‡„‡–™‡‡Ž‘–ˆ‘”‡Ž‹‰‹„Ž‡•ǡ‹†‡Ž•ǡˆ—•‹‘•ǡ•ǡƒ†ƒŽŽ”‡’‘”–ƒ„Ž‡˜ƒ”‹ƒ–•–‘‰‡–Š‡”ƒ”‡
    •Š‘™‹Table 21Ǥ ‘”‡ƒ Š‘ˆ–Š‡•‡˜ƒ”‹ƒ–•ǡ–Š‡”‡™‡”‡ͳʹ’ƒ‹”™‹•‡ ‘’ƒ”‹•‘•Ǥ

    Table 21. Between-Lot APA Summary


    Variant Lot
    Variant Type Comparisons Concordant Discordant APA
     Ͷ͹ ͷ͵ͳ ʹ͸ ͻ͹Ǥ͸Ψ
    †‡Ž ͳͳ ͳ͵ʹ Ͳ ͳͲͲǤͲΨ
     ͺ ͷ͵ ͸ ͻͶǤ͸Ψ
    —•‹‘ Ͷ Ͷͺ Ͳ ͳͲͲǤͲΨ
     ͹Ͳ ͹͸Ͷ ͵ʹ ͻͺǤͲΨ

    Š‡„‡–™‡‡ǦŽ‘–ˆ‘”ƒŽŽ˜ƒ”‹ƒ––›’‡•–‘‰‡–Š‡”™ƒ•ͻͺǤͲΨǢ„‡–™‡‡Ž‘–™ƒ•ͻͻǤͻΨƒ ”‘••ƒŽŽ
    ”‡’‘”–ƒ„Ž‡’‘•‹–‹‘•ƒ†˜ƒ”‹ƒ–•ǤŠ‹••–ƒ–‹•–‹ ‹ Ž—†‡•ƒŽŽ ƒŽŽ‡†˜ƒ”‹ƒ–•‹–‡•ǡ‘–Œ—•––Š‡‡Ž‹‰‹„Ž‡
    ˜ƒ”‹ƒ–••‹–‡•„ƒ•‡†‘‘‹–Š‡•‘—” ‡•ƒ’Ž‡•ǡ•‘‹ Ž—†‡•’‘•‹–‹‘•™‹–Š‡š’‡ –‡†•–‘ Šƒ•–‹ 
    †‡–‡ –‹‘†—‡–‘Ž‘™—–ƒ–‘Ž‡ —Ž‡ ‘—–ǤŠ‡—„‡”‘ˆ’‘•‹–‹‘•‡˜ƒŽ—ƒ–‡†™ƒ•Ͷ͸ǡʹͳ͹—‹“—‡
    ƒ†‹†‡Ž”‡’‘”–ƒ„Ž‡’‘•‹–‹‘•ǡʹ•ǡƒ†Ͷˆ—•‹‘•Ǥ
    ‘–ƒ„Ž›ǡˆ‘”ERBB2ƒ’Ž‹ˆ‹ ƒ–‹‘•ǡ™‹–Š‹ƒ†„‡–™‡‡ǦŽ‘–™‡”‡‘„•‡”˜‡†–‘„‡ͺͲǤͲΨƒ†
    ͺͷǤͲΨǡ”‡•’‡ –‹˜‡Ž›ǡ†—‡–‘˜ƒ”‹ƒ–‹‘‹ˆ‘ ƒŽ‹–›†‡–‡”‹ƒ–‹‘Ǥ’‡ ‹ˆ‹ ƒŽŽ›ǡ•‘‡‘ˆ–Š‡”‡’Ž‹ ƒ–‡•
    ™‡”‡†‡–‡”‹‡†–‘„‡ˆ‘ ƒŽŽ›ƒ’Ž‹ˆ‹‡†ǡƒ†–Š—•”‡’‘”–‡†„›–Š‡ƒ••ƒ›ǡƒ†•‘‡™‡”‡†‡–‡”‹‡†
    –‘„‡ƒ‡—’Ž‘‹†ƒ†–Š—•”‡’‘”–‡†‡‰ƒ–‹˜‡ƒ•–Š‡ —ƒ”†ƒ–͵͸Ͳš”‡’‘”–••‘Ž›ˆ‘”ˆ‘ ƒŽ
    ƒ’Ž‹ˆ‹ ƒ–‹‘•ƒ†‘– Š”‘‘•‘‡Ǧƒ”ƒ’Ž‹ˆ‹ ƒ–‹‘•Ǥ
    ƒ††‹–‹‘–‘–Š‡ƒ‹•–—†›ǡ•—’’Ž‡‡–ƒ”›•ƒ’Ž‡•ǡ•–ƒ”–‹‰ˆ”‘’Žƒ•ƒǡ™‡”‡’”‘ ‡••‡†–‘
    ‡˜ƒŽ—ƒ–‡’”‡ ‹•‹‘ˆ”‘‡š–”ƒ –‹‘Ǥ —•‹‘•ƒ’Ž‡•™‡”‡ ”‡ƒ–‡†„›†‹Ž—–‹‰ ˆ‡š–”ƒ –‡†ˆ”‘
    ‡ŽŽŽ‹‡•Šƒ”„‘”‹‰ROS1ƒ†NTRK1ˆ—•‹‘•‹–‘’Žƒ•ƒ‘ˆ Ž‹‹ ƒŽŽ—‰ ƒ ‡”•ƒ’Ž‡•‡‰ƒ–‹˜‡ˆ‘”
    ˆ—•‹‘•ǤŠ‡•‡ ‘–”‹˜‡†’Žƒ•ƒ•ƒ’Ž‡•™‡”‡‡˜ƒŽ—ƒ–‡†‹Ž‹‡—‘ˆ Ž‹‹ ƒŽ•ƒ’Ž‡•ˆ‘”–Š‹••–—†›†—‡
    –‘–Š‡”ƒ”‹–›‘ˆ–Š‡•‡ƒŽ–‡”ƒ–‹‘•ǤŽƒ•ƒ™ƒ•’”‘ ‡••‡†ˆ”‘‡š–”ƒ –‹‘–‘•‡“—‡ ‹‰‘–Š‡•ƒ‡
    ʹͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    „ƒ– Š‡•ƒ•–Š‡”‡•–‘ˆ–Š‡•–—†›•ƒ’Ž‡•ǤŠ‡ˆ—•‹‘ ˆ™ƒ•†‹Ž—–‡†–‘δͲǤʹΨ ˆ‘”ROS1ƒ†
    NTRK1ƒ–̱͵Ͳ‰‹’—–ǤŠ‡”‡™ƒ•ͳͲͲΨ†‡–‡ –‹‘ȋ͸Ȁ͸Ȍƒ ”‘••”‡ƒ‰‡–Ž‘–•ˆ‘”„‘–Šˆ—•‹‘•™Š‡
    –‡•–‡†ƒ–ͲǤͳͷΨ ƒ–ƒ’’”‘š‹ƒ–‡Ž›͵Ͳ‰‘ˆ ˆǤ

    g. Precision from mutation-negative samples


    ƒ’Ž‡•ˆ”‘Š‡ƒŽ–Š›†‘‘”•™‡”‡’”‡Ǧ• ”‡‡‡†„›ƒ‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡†‘”–Š‘‰‘ƒŽ‡–Š‘†Ǥ
    —–ƒ–‹‘‡‰ƒ–‹˜‡•ƒ’Ž‡•„›–Š‡‘”–Š‘‰‘ƒŽ‡–Š‘†™‡”‡–‡•–‡†„› —ƒ”†ƒ–͵͸Ͳš‹–Š”‡‡
    ”‡’”‘†— ‹„‹Ž‹–› ‘†‹–‹‘•ȋi.e.ǡ†‹ˆˆ‡”‡–”‡ƒ‰‡–Ž‘–•ǡ‘’‡”ƒ–‘”•ǡ‹•–”—‡–•ǡƒ††ƒ›•ȌǤ ‘—”
    ”‡’Ž‹ ƒ–‡•ˆ”‘‡ƒ Š†‘‘”™‡”‡–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸Ͳšƒ ”‘••–Š‡†‹ˆˆ‡”‡–”‡’”‘†— ‹„‹Ž‹–›
    ‘†‹–‹‘•ǤŠ‡•–—†›†‡‘•–”ƒ–‡†ƒ•ƒ’Ž‡ǦŽ‡˜‡Žǡ™‹–Š‹Ǧ ‘†‹–‹‘‘ˆͻ͹ǤͶΨƒ†•ƒ’Ž‡ǦŽ‡˜‡Ž
    „‡–™‡‡Ǧ ‘†‹–‹‘‘ˆͻ͹Ǥ͵ΨǤŠ‡™‹–Š‹Ǧ ‘†‹–‹‘™ƒ•ͻͻǤ͸Ψƒ†„‡–™‡‡Ǧ ‘†‹–‹‘
    ™ƒ•ͻͻǤ͸Ψˆ‘”͹˜ƒ”‹ƒ–•–Šƒ–Šƒ†ƒ’‘•‹–‹˜‡ ƒŽŽ‹ƒ–Ž‡ƒ•–‘‡ ‘†‹–‹‘Ǥ‹–Š‹Ǧ ‘†‹–‹‘ƒ†
    „‡–™‡‡Ǧ ‘†‹–‹‘˜ƒŽ—‡•™‡”‡ͳͲͲǤͲΨˆ‘”ƒŽŽš˜ƒ”‹ƒ–•ȋ EGFRͺͷͺǡEGFR͹ͻͲǡEGFR
    ‡š‘ͳͻ†‡Ž‡–‹‘•ǡƒ†EGFR‡š‘ʹͲ‹•‡”–‹‘•Ȍƒ† ƒ–‡‰‘”›ʹ˜ƒ”‹ƒ–•Ǥ
    ƒ’Ž‡•ˆ”‘Š‡ƒŽ–Š›†‘‘”•ȋKRAS ͳʹ‡‰ƒ–‹˜‡•Ȍǡ’”‡Ǧ• ”‡‡‡†„›ƒ‡š–‡”ƒŽŽ›˜ƒŽ‹†ƒ–‡†
    ‘”–Š‘‰‘ƒŽ‡–Š‘†ǡ™‡”‡”‡ƒƒŽ›œ‡†•’‡ ‹ˆ‹ ƒŽŽ›ˆ‘”KRAS ͳʹ—–ƒ–‹‘–‘†‡–‡”‹‡‹ˆˆƒŽ•‡
    ’‘•‹–‹˜‡•™‡”‡†‡–‡ –‡†ƒ ”‘••”‡’Ž‹ ƒ–‡•‘” ‘†‹–‹‘•ǤŠ‡•–—†›†‡‘•–”ƒ–‡†ƒ•ƒ’Ž‡ǦŽ‡˜‡Žǡ
    ™‹–Š‹Ǧ ‘†‹–‹‘ƒ˜‡”ƒ‰‡‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ȋȌ‘ˆͳͲͲΨƒ†ƒ•ƒ’Ž‡ǦŽ‡˜‡Ž„‡–™‡‡Ǧ ‘†‹–‹‘
    ‘ˆͳͲͲΨˆ‘”KRAS ͳʹǤ

    ͸Ǥ͸Ǥ ”‘••Ǧ‘–ƒ‹ƒ–‹‘Ȁƒ””›Ǧ˜‡”
    Š‡ ƒ””›‘˜‡”Ȁ ”‘••Ǧ ‘–ƒ‹ƒ–‹‘•–—†›‡˜ƒŽ—ƒ–‡†–Š‡’”‡˜ƒŽ‡ ‡‘ˆ ”‘••Ǧ ‘–ƒ‹ƒ–‹‘™Š‡
    ƒ–‡”‹ƒŽ‹•–”ƒ•ˆ‡””‡†„‡–™‡‡•ƒ’Ž‡•‹–Š‡•ƒ‡„ƒ– Šƒ† ƒ””›Ǧ‘˜‡”™Š‡ƒ–‡”‹ƒŽ‹•
    –”ƒ•ˆ‡””‡†„‡–™‡‡•ƒ’Ž‡•ƒ ”‘••„ƒ– Š‡•’”‘ ‡••‡†•‡“—‡–‹ƒŽŽ›‘–Š‡•ƒ‡‹•–”—‡–—•‹‰
    —ƒ”†ƒ–͵͸ͲšǤ
    –‘–ƒŽ‘ˆ͵ͷʹ’Žƒ•ƒ•ƒ’Ž‡•ƒ ”‘••ͺ„ƒ– Š‡•ȋͶͶ•ƒ’Ž‡•Ȁ„ƒ– Ššͺ„ƒ– Š‡•Ȍ™‡”‡”—‹ƒ
    ‘•‡ —–‹˜‡‘”†‡”ƒ ”‘••‹•–”—‡–•™‹–Š‹–Š‡ƒƒŽ›–‹ ƒŽƒ —”ƒ ›•–—†›ƒ†•‡“—‡ ‡†‘ͳ͸
    ˆŽ‘™ ‡ŽŽ•Ǥ
    Š‡”‡™ƒ•‘‡˜‹†‡ ‡‘ˆŠ‹‰Š’‘•‹–‹˜‡˜ƒ”‹ƒ–•ˆ”‘‡ƒ”Ǧ„›™‡ŽŽ•†‡–‡ –‡†‹‡‰ƒ–‹˜‡•ƒ’Ž‡•Ǥ 
    ‘ Ž—•‹‘ǡ‘ ƒ””›‘˜‡”‘” ”‘••Ǧ ‘–ƒ‹ƒ–‹‘™ƒ•‘„•‡”˜‡†‹͵ͷʹ•ƒ’Ž‡•’”‘ ‡••‡†ƒ ”‘••ͺ
    ‘•‡ —–‹˜‡„ƒ– Š‡•Ǥ

    ͸Ǥ͹Ǥ —ƒ”†ƒ†‹‰Ȁ‘„—•–‡••
    Š‡’—”’‘•‡‘ˆ–Š‡‰—ƒ”†„ƒ†‹‰•–—†›™ƒ•–‘‡˜ƒŽ—ƒ–‡ ˆ‹’—–ƒ––Š‡‹‹—‹’—–ƒ‘—–
    ȋͷ‰Ȍƒ†–Š‡ƒš‹—ƒ‘—–ȋ͵Ͳ‰Ȍǡƒ†ƒ’–‡”˜‘Ž—‡–‘Ž‡”ƒ ‡•ˆ‘”Ž‹‰ƒ–‹‘•–‡’•ǡŠ›„”‹†‹œƒ–‹‘
    –‹‡–‘Ž‡”ƒ ‡•‹–Š‡‡”‹ Š‡–’”‘ ‡••ƒ†™ƒ•Š„—ˆˆ‡”ʹ–‡’‡”ƒ–—”‡–‘Ž‡”ƒ ‡•‹–Š‡
    ‡”‹ Š‡–’”‘ ‡••ȋTable 22 Ǥ

    Table 22. Guard Banding Study Overview


    Guard Banding Condition Reference condition Condition 1 Condition 2
    ˆ ’—–ƒ‘—– ͷ‰ ʹǤͷ‰ Ͷ‰
    ˆ ’—–ƒ‘—– ͵Ͳ‰ ͵͸‰ Ͷͷ‰
    †ƒ’–‡”˜‘Ž—‡ ͳͺǤͲρ ͳ͸Ǥʹρ ͳͻǤͺρ
    ›„”‹†‹œƒ–‹‘‹‡ ͳʹŠ‘—”• ʹͶŠ‘—”• Ȁ
    ƒ•Š—ˆˆ‡”‡’‡”ƒ–—”‡ ͹ͳι ͹Ͳι ͹ʹι

    ʹʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‡–ƒ”‰‡–‡†˜ƒ”‹ƒ–•”‡’”‡•‡–ƒ–‹˜‡‘ˆ•ǡ‹†‡Ž•ǡ•ǡƒ†ˆ—•‹‘•™‡”‡–‡•–‡†‹ʹ˜ƒ”‹ƒ–’‘‘Ž•Ǥ
    ƒ Š˜ƒ”‹ƒ–’‘‘Ž™ƒ•’”‡’ƒ”‡†„›†‹Ž—–‹‰‡‹–Š‡” Ž‹‹ ƒŽ‘” ‡ŽŽŽ‹‡Ǧ†‡”‹˜‡† ˆ•ƒ’Ž‡•’‘•‹–‹˜‡
    ˆ‘”ƒ‰‹˜‡„‹‘ƒ”‡”™‹–Š—–ƒ–‹‘Ǧ‡‰ƒ–‹˜‡ ˆ†‡”‹˜‡†ˆ”‘‡‹–Š‡”‘”„”‡ƒ•– ƒ ‡”
    ’ƒ–‹‡–•–ƒ”‰‡–‹‰‡ƒ Š˜ƒ”‹ƒ––‘ͳȂʹš‘Ǥ‡Š—†”‡†ˆ‘—”ȋͳͲͶȌ‘ˆ–Š‡ͳʹ͸•ƒ’Ž‡•’ƒ••‡†’‘•–Ǧ
    •‡“—‡ ‹‰‡–”‹ •ǡ™‹–Š‘Ž›–Š‡ʹǤͷ‰ ˆ‹’—– ‘†‹–‹‘ˆƒ‹Ž‹‰–‘”‡ƒ Š–Š‡‹‹—
    •ƒ’Ž‡—„‡”Ǥ
    ŽŽ•ȋ—ƒŽ‹–ƒ–‹˜‡‡–‡ –‹‘ƒ–‡•Ȍ™‡”‡ͳͲͲΨǡ‡š ‡’–ˆ‘”–Š‡Ͷ‰‹’—– ‘†‹–‹‘ǡ™Š‹ Š•Š‘™‡†
    ƒ‘ˆͻ͹ǤʹΨǡ™‹–Š‘‡˜ƒ”‹ƒ–ȋEGFR͹͸͹̴͹͸ͻ†—’Ȍ‹••‹‰‹‘‡‘ˆͶ‰‹’—–•ƒ’Ž‡•ȋTable
    23ȌǤŠ‡™ƒ•ͳͲͲΨ™‹–ŠƒŽ‘™‡”Ž‹‹–‘ˆ–Š‡ͻͷΨ ‘ˆ‹†‡ ‡‹–‡”˜ƒŽȋ Ȍ‘ˆͺͷǤͶ͹ΨǤ ‘”
    ‡ƒ Š–‡•–‡†‰—ƒ”†„ƒ†‹‰ ‘†‹–‹‘ǡƒŽŽ–Š‡ ™‡”‡Š‹‰Š‡”–ŠƒͺͲΨǡ‡‡–‹‰–Š‡ƒ ‡’–ƒ ‡
    ”‹–‡”‹ƒǤ
    ™ƒ•ƒƒŽ›œ‡†„›ƒ••‡••‹‰ˆ‘”–Š‡˜ƒ”‹ƒ–•–ƒ”‰‡–‡†‹‡ƒ Š’‘‘ŽǤ‘‡‘ˆ–Š‡–ƒ”‰‡–‡†˜ƒ”‹ƒ–•
    ™‡”‡‘„•‡”˜‡†ƒ ”‘•••ƒ’Ž‡•ǡ”‡•—Ž–‹‰‹ƒͳͲͲΨ’‡”Ǧ•ƒ’Ž‡ƒ ”‘••ƒŽŽ ‘†‹–‹‘•Ǥ

    Table 23. Guard Banding Results Summary


    Guard Banding
    Condition Reference Condition Condition 1 Condition 2
    ˆ ’—–‘—–ȋͷ‰Ȍ ͷ͸Ȁͷ͸αͳͲͲΨ Ȁ ͵ͷȀ͵͸αͻ͹ǤʹʹΨ
    ȏͻͷΨ Ȑ ȏͻ͵Ǥ͸ʹΨǡͳͲͲΨȐ ȋ›†‡•‹‰ǡ–Š‡‡–”‹  ȏͺͷǤͶ͹ΨǡͻͻǤͻ͵ΨȐ
    ˆƒ‹Ž‡†ƒ––Š‹•Ž‡˜‡ŽȌ
    ˆ ’—–‘—–ȋ͵Ͳ‰Ȍ ͷͲȀͷͲαͳͲͲΨ Ͷ͸ȀͶ͸αͳͲͲΨ ͷͲȀͷͲαͳͲͲΨ
    ȏͻͷΨ Ȑ ȏͻʹǤͺͻΨǡͳͲͲΨȐ ȏͻʹǤʹͻΨǡͳͲͲΨȐ ȏͻʹǤͺͻΨǡͳͲͲΨȐ
    †ƒ’–‡”‘Ž—‡ ͷ͸Ȁͷ͸αͳͲͲΨ ͸ͲȀ͸ͲαͳͲͲΨ ͷͲȀͷͲαͳͲͲΨ
    ȏͻͷΨ Ȑ ȏͻ͵Ǥ͸ʹΨǡͳͲͲΨȐ ȏͻͶǤͲͶΨǡͳͲͲΨȐ ȏͻʹǤͺͻΨǡͳͲͲΨȐ
    ›„”‹†‹œƒ–‹‘‹‡ ͷ͸Ȁͷ͸αͳͲͲΨ ͸ͲȀ͸ͲαͳͲͲΨ Ȁ
    ȏͻͷΨ Ȑ ȏͻ͵Ǥ͸ʹΨǡͳͲͲΨȐ ȏͻͶǤͲͶΨǡͳͲͲΨȐ
    ƒ•Š—ˆˆ‡”‡’‡”ƒ–—”‡ ͷ͸Ȁͷ͸αͳͲͲΨ ͸ͲȀ͸ͲαͳͲͲΨ ͸ͲȀ͸ͲαͳͲͲΨ
    ȏͻͷΨ Ȑ ȏͻ͵Ǥ͸ʹΨǡͳͲͲΨȐ ȏͻͶǤͲͶΨǡͳͲͲΨȐ ȏͻͶǤͲͶΨǡͳͲͲΨȐ
    Ȁǣ‘–’’Ž‹ ƒ„Ž‡ȋ‡‡Table 22ȌǢǣ“—ƒŽ‹–ƒ–‹˜‡†‡–‡ –‹‘”ƒ–‡Ǥ
    Š‡•‡”‡•—Ž–•†‡‘•–”ƒ–‡–Š‡”‘„—•–‡••‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘˜ƒ”‹ƒ–‹‘‹ ˆ‹’—–ȋͶ‰–‘Ͷͷ
    ‰Ȍǡ‡”‹ Š‡–™ƒ•Š„—ˆˆ‡”–‡’‡”ƒ–—”‡ǡ‡”‹ Š‡–Š›„”‹†‹œƒ–‹‘–‹‡ǡƒ†Ž‹„”ƒ”›ƒ†ƒ’–‡”
    ˜‘Ž—‡Ǥ

    ͸ǤͺǤ ‡ƒ‰‡–‘– –‡” Šƒ‰‡ƒ„‹Ž‹–›


    ‡ƒ‰‡–•Ž‘–‹–‡” Šƒ‰‡ƒ„‹Ž‹–›™ƒ•ƒ••‡••‡†„›–‡•–‹‰–™‘ ˆ•ƒ’Ž‡’‘‘Ž• ‘–ƒ‹‹‰ͳ͸
    ƒŽ–‡”ƒ–‹‘•ǡͻ˜ƒ”‹ƒ–•‹’‘‘Žͳƒ†͹˜ƒ”‹ƒ–•‹’‘‘Žʹǡ‹ˆ‹˜‡”‡’Ž‹ ƒ–‡•—•‹‰–™‘†‹ˆˆ‡”‡–Ž‘–•‘ˆ
    —ƒ”†ƒ–͵͸Ͳšƒ’Ž‡”‡’ƒ”ƒ–‹‘‹–‹•‡˜‡†‹ˆˆ‡”‡–Ž‘– ‘„‹ƒ–‹‘•Ǥ ‘”–Š‡•ƒ’Ž‡
    ”‡’Ž‹ ƒ–‡•–Šƒ–’”‘ ‡‡†‡†–‘•‡“—‡ ‹‰ǡƒŽŽ‡––Š‡’‡”ˆ‘”ƒ ‡‡–”‹ •Ǥ‹–‘– –‡” Šƒ‰‡ƒ„‹Ž‹–›
    ‘ˆ —ƒ”†ƒ–͵͸Ͳ„‘š‡•™ƒ•‡˜ƒŽ—ƒ–‡†„ƒ•‡†‘–Š‡”ƒ–‡‘ˆ’‘•‹–‹˜‡ƒ‰”‡‡‡–ˆ‘”†‡–‡ –‹‘‘ˆ
    –ƒ”‰‡–‡†˜ƒ”‹ƒ–•Ǥ
    —–‘ˆ͹Ͳ•ƒ’Ž‡•ǡ͸ͺ’ƒ••‡†‡–”‹ •ȋͻ͹Ψ’ƒ••”ƒ–‡ȌǤŠ‡”ƒ–‡‘ˆ“—ƒŽ‹–ƒ–‹˜‡ƒ‰”‡‡‡–”ƒ–‡
    ȋȌǡi.e.ǡ–Š‡ƒ‰”‡‡‡–™‹–Š–Š‡ƒŒ‘”‹–› ƒŽŽˆ‘”„ƒ•‡Ž‹‡”‡ƒ‰‡–™ƒ• ƒŽ —Žƒ–‡†Ǥ™ƒ•†‡ˆ‹‡†
    ƒ•–Š‡—„‡”‘ˆ’‘•‹–‹˜‡Ž›†‡–‡ –‡†–ƒ”‰‡–‡†˜ƒ”‹ƒ–•ƒ ”‘••‡Ž‹‰‹„Ž‡•ƒ’Ž‡•ȋȌ†‹˜‹†‡†„›–Š‡–‘–ƒŽ
    —„‡”‘ˆ–ƒ”‰‡–‡†˜ƒ”‹ƒ–•–‡•–‡†ƒ ”‘••‡Ž‹‰‹„Ž‡•ƒ’Ž‡•ȋȌǡ‡š’”‡••‡†ƒ•ƒ’‡” ‡–ƒ‰‡ȋͳͲͲȗ
    ȀȌǤ”ƒ‰‡†ˆ”‘ͻͳǤ͸Ψ–‘ͻͺǤ͹ΨǤŠ‡”‡™ƒ•ͳͲͲǤͲؐ‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ƒ‘‰‡š’‡ –‡†
    ‡‰ƒ–‹˜‡•‹–‡•™‹–Š‹”‡•’‡ –‹˜‡’‘‘Ž”‡’Ž‹ ƒ–‡•Ǥ

    ʹ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Š‡’ƒ‡ŽǦ™‹†‡ƒ••‡••‡–‘ˆ™ƒ•ͻͻǤͻΨ ƒŽ —Žƒ–‡†ˆ”‘‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•‹–‡•ƒ ”‘••–Š‡
    —ƒ”†ƒ–͵͸Ͳš”‡’‘”–ƒ„Ž‡”ƒ‰‡–Šƒ–ƒ”‡‘–†‡–‡ –‡†‹–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘”‡’”‡•‡–•
    ‘–ˆ‘”ƒŽŽ ‘„‹ƒ–‹‘•–‡•–‡†Ǥ

    ͸ǤͻǤ –ƒ„‹Ž‹–›

    a. Reagent Stability
    Š‡•–ƒ„‹Ž‹–›‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ’Ž‡”‡’ƒ”ƒ–‹‘‹–Ž‘–•—•‡†‹•ƒ’Ž‡’”‘ ‡••‹‰ˆ‘”
    —ƒ”†ƒ–͵͸Ͳš™‡”‡‡˜ƒŽ—ƒ–‡†‹–Š‹••–—†›ǤŠ”‡‡Ž‘–•‘ˆ‹†‡–‹ ƒŽ”‡ƒ‰‡–•™‡”‡•–‘”‡†—†‡”–Š‡
    •’‡ ‹ˆ‹‡†•–‘”ƒ‰‡ ‘†‹–‹‘•ˆ‘”‡ƒ Š„‘šƒ†–Š‡–‡•–‡†ƒ–†‡ˆ‹‡†–‹‡’‘‹–•—•‹‰–™‘ ˆ
    •ƒ’Ž‡’‘‘Ž•–Šƒ– ‘–ƒ‹‡†‹–‘–ƒŽͳ͸‘™˜ƒ”‹ƒ–•ǡͻ˜ƒ”‹ƒ–•‹’‘‘Žͳƒ†͹˜ƒ”‹ƒ–•‹’‘‘ŽʹǤ
    †‡”–Š‡–‡•–‡† ‘†‹–‹‘•ǡ”‡•—Ž–•ˆ”‘‡ƒ Š–‹‡’‘‹–ǡ͵ǡͶǡ͹ǡͳͲǡͳ͵ƒ†ͳͻ‘–Š•™‡”‡
    ‘’ƒ”‡†ƒ‰ƒ‹•–•ƒ’Ž‡•–‡•–‡†ƒ–†ƒ›Ͳȋ–‹‡’‘‹–ͲȌǤŠ‡ —ƒ”†ƒ–͵͸Ͳ„‘š‡•™‡”‡–‡•–‡†ƒ–
    ‡ƒ Š–‹‡’‘‹–™‹–Šˆ‹˜‡ȋͷȌ”‡’Ž‹ ƒ–‡•’‡”‡ƒ Š‘ˆ–Š‡–™‘—‹“—‡•ƒ’Ž‡’‘‘Ž•ƒ–ͷ‰ ˆ‹’—–Ǥ
    —ƒŽ‹–ƒ–‹˜‡†‡–‡ –‹‘”ƒ–‡•ȋȌǡ™Š‹ Š‹•„ƒ•‡†‘–Š‡ƒ‰”‡‡‡–™‹–Š–Š‡ƒŒ‘”‹–› ƒŽŽƒ–Ͳˆ‘”–Š‡
    —„‡”‘ˆ–ƒ”‰‡–‡†˜ƒ”‹ƒ–•†‡–‡ –‡†ǡ™‡”‡ƒ••‡••‡†’‡”Ž‘–Ȁ’‡”–‹‡’‘‹–Ǥ™ƒ•†‡ˆ‹‡†ƒ•–Š‡
    —„‡”‘ˆ’‘•‹–‹˜‡Ž›†‡–‡ –‡†–ƒ”‰‡–‡†˜ƒ”‹ƒ–•–Šƒ–™‡”‡’‘•‹–‹˜‡Ž›†‡–‡ –‡†‹–Š‡„ƒ•‡Ž‹‡
    ‘†‹–‹‘ƒ ”‘••‡Ž‹‰‹„Ž‡•ƒ’Ž‡•ȋȌ†‹˜‹†‡†„›–Š‡–‘–ƒŽ—„‡”‘ˆ’‘•‹–‹˜‡Ž›†‡–‡ –‡†–ƒ”‰‡–‡†
    ˜ƒ”‹ƒ–•–‡•–‡†ƒ ”‘••‡Ž‹‰‹„Ž‡•ƒ’Ž‡•ȋȌǡ‡š’”‡••‡†ƒ•ƒ’‡” ‡–ƒ‰‡ȋͳͲͲȗȀȌǤŠ‡•–—†›•Š‘™‡†
    ‘•‹‰‹ˆ‹ ƒ–†‹ˆˆ‡”‡ ‡„‡–™‡‡–‹‡’‘‹–• ‘’ƒ”‡†–‘Ͳˆ‘”ƒŽŽ–Š”‡‡Ž‘–•ȋƒŽ’ŠƒαͲǤͲͷȌǡ
    †‡‘•–”ƒ–‹‰–Šƒ––Š‡”‡™ƒ•‘•‹‰‹ˆ‹ ƒ–†‡ Ž‹‡‹†‡–‡ –‹‘”ƒ–‡•‘˜‡”–Š‡ ‘—”•‡‘ˆ–Š‡•–—†›Ǥ
    Š‡“—ƒŽ‹–ƒ–‹˜‡†‡–‡ –‹‘”ƒ–‡ǡ ƒŽ —Žƒ–‡†ˆ”‘–ƒ”‰‡–‡†•‹–‡•”ƒ‰‡†„‡–™‡‡ͻͷǤͲΨƒ†ͳͲͲǤͲΨ„›
    –‹‡’‘‹–ǤŽŽ‘ˆ–Š‡‡š’‡ –‡†‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•™‡”‡‘„•‡”˜‡†ƒ•‡‰ƒ–‹˜‡ ƒŽŽ•ƒ ”‘••ƒŽŽ”‡’Ž‹ ƒ–‡•ǡ
    ‹†‹ ƒ–‹‰ͳͲͲؐ‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ƒ‘‰ƒŽŽ–ƒ”‰‡–‡†˜ƒ”‹ƒ–•‡š’‡ –‡†–‘„‡‡‰ƒ–‹˜‡ƒ ”‘•••–—†›
    ‘†‹–‹‘•ǤŠ‡’ƒ‡ŽǦ™‹†‡ƒ••‡••‡–‘ˆ™ƒ•ͻͻǤͻΨ ƒŽ —Žƒ–‡†ˆ”‘‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•‹–‡•
    ƒ ”‘••–Š‡ —ƒ”†ƒ–͵͸Ͳš”‡’‘”–ƒ„Ž‡”ƒ‰‡–Šƒ–ƒ”‡‘–†‡–‡ –‡†‹–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘
    ”‡’”‡•‡–‹‰–‹‡Ͳˆ‘”ƒŽŽ–‹‡’‘‹–•–‡•–‡†Ǥ
    ƒ”‹ƒ–†‡–‡ –‹‘’‡”ˆ‘”ƒ ‡™ƒ••–ƒ„Ž‡ˆ‘”ƒ Žƒ‹‡†•Š‡ŽˆŽ‹ˆ‡‘ˆͳͺ‘–Š•Ǥ

    b. Whole Blood Stability


    Š‡‘„Œ‡ –‹˜‡‘ˆ–Š‹••–—†›™ƒ•–‘†‡‘•–”ƒ–‡–Š‡•–ƒ„‹Ž‹–›‘ˆ™Š‘Ž‡„Ž‘‘†•’‡ ‹‡•—•‡†ˆ‘”
    —ƒ”†ƒ–͵͸Ͳš ‘ŽŽ‡ –‡†‹–Š‡ —ƒ”†ƒ–͵͸Ͳǡ–Šƒ–‹•‹–”‡ ‡ŽŽǦ ”‡‡•ǡƒ ”‘••–Š‡
    ‡š’‡ –‡†”ƒ‰‡‘ˆ•ƒ’Ž‡–”ƒ•’‘”–ƒ†•–‘”ƒ‰‡ ‘†‹–‹‘•ˆ‘”—’–‘͹†ƒ›•ƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘
    ’”‹‘”–‘’Žƒ•ƒ‹•‘Žƒ–‹‘ǤŠ‡•–ƒ„‹Ž‹–›‘ˆ™Š‘Ž‡„Ž‘‘†—•‡†ˆ‘” —ƒ”†ƒ–͵͸Ͳš™ƒ•‡˜ƒŽ—ƒ–‡†„›
    ‘ŽŽ‡ –‹‰Ͷˆ”‡•Š™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡•ˆ”‘ͳ͸ ƒ ‡”’ƒ–‹‡–•Ǥ ”‘‡ƒ Š’ƒ–‹‡–ǡ‘‡–—„‡™ƒ•
    ’”‘ ‡••‡†–‘’Žƒ•ƒͳ†ƒ›ƒˆ–‡”„Ž‘‘††”ƒ™ȋ•–‘”ƒ‰‡ƒ–”‘‘–‡’‡”ƒ–—”‡ȌǤŽƒ•ƒ™ƒ•–Š‡•Š‹’’‡†
    ‘†”›‹ ‡–‘ —ƒ”†ƒ– ‡ƒŽ–ŠǤŠ‹• ‘•–‹–—–‡†–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘Ǥ ƒ††‹–‹‘–‘–Š‡”‡ˆ‡”‡ ‡
    –—„‡ǡ–Š”‡‡‘”‡„Ž‘‘†–—„‡•’‡”†‘‘”™‡”‡•Š‹’’‡†ƒ•™Š‘Ž‡„Ž‘‘†–‘ —ƒ”†ƒ– ‡ƒŽ–Šƒ†
    •—„Œ‡ –‡†–‘‘†‹–‹‘ͳȋ—‡”’”‘ˆ‹Ž‡Ȍǡ‘†‹–‹‘ʹȋ‹–‡”’”‘ˆ‹Ž‡Ȍ‘”‘†‹–‹‘͵ȋ‘‘
    –‡’‡”ƒ–—”‡Ȍƒ•ˆ‘ŽŽ‘™ǣ
    x ‡ˆ‡”‡ ‡‘†‹–‹‘ǣŽƒ•ƒ’”‘ ‡••‹‰ͳ†ƒ›ƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘
    x ‘†‹–‹‘ͳǣ—‡””‘ˆ‹Ž‡–‘”ƒ‰‡ǣͶŠƒ–ʹʹιǡ͸Šƒ–͵͹ιǡƒ†ͷ͸Šƒ–ʹʹιǡ͸Šƒ–͵͹ιǡ’Ž—•
    ”‡ƒ‹‹‰–‹‡ƒ–”‘‘–‡’‡”ƒ–—”‡Ǥ
    x ‘†‹–‹‘ʹǣ‹–‡””‘ˆ‹Ž‡–‘”ƒ‰‡ǣͶŠƒ–ͳͺιǡ͸Šƒ–Ͳιǡͷ͸Šƒ–ͳͲιǡƒ†͸Šƒ–Ͳι’Ž—•
    ”‡ƒ‹‹‰–‹‡ƒ–”‘‘–‡’‡”ƒ–—”‡
    x ‘†‹–‹‘͵ǣ‘‘‡’‡”ƒ–—”‡–‘”ƒ‰‡ǣ–‘”ƒ‰‡ƒ–”‘‘–‡’‡”ƒ–—”‡ͳͺǦʹͷι

    ʹͶ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ˆ–‡” ‘†‹–‹‘‹‰ǡ’Žƒ•ƒ™ƒ•‹•‘Žƒ–‡†‘–Š‡ͺ–Š†ƒ›ƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†”—‘–Š‡
    —ƒ”†ƒ–͵͸ͲšǤ
    ŽŽ͸Ͷ•ƒ’Ž‡•’ƒ••‡†ƒŽŽƒ†™‡”‡‹ Ž—†‡†‹ƒƒŽ›•‹•ǤŽŽ•–‘”ƒ‰‡ ‘†‹–‹‘•†‡‘•–”ƒ–‡†
    ƒ ‡’–ƒ„Ž‡’‡”ˆ‘”ƒ ‡ǤŽŽ•ƒ’Ž‡•‹‡ƒ Š‰”‘—’†‡‘•–”ƒ–‡†ƒ ‡’–ƒ„Ž‡•ƒ’Ž‡ǦŽ‡˜‡Ž‘Ž‡ —Ž‡
    ”‡ ‘˜‡”›ƒ•ƒ••‡••‡†„›†‡’–Š‘ˆ ‘˜‡”ƒ‰‡ƒ ”‘••–Š‡’ƒ‡ŽǤ ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹–‡•–
    ‘†‹–‹‘‘˜‡”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘‘”–‹‡œ‡”‘”ƒ‰‡†ˆ”‘ͲǤͻͲ–‘ͲǤͻ͹Ǥ
    š‘ǦŽ‡˜‡Ž ‘˜‡”ƒ‰‡™ƒ•ƒŽ•‘ƒ ‡’–ƒ„Ž‡ˆ‘”ƒŽŽ ‘†‹–‹‘•‡˜ƒŽ—ƒ–‡†ǤŠ‡ˆ”ƒ –‹‘‘ˆ‡š‘•™‹–Š
    ”‡Žƒ–‹˜‡‡š‘Ž‡˜‡Ž ‘˜‡”ƒ‰‡†‹ˆˆ‡”‡ ‡„‡–™‡‡ ‘†‹–‹‘ƒ†”‡ˆ‡”‡ ‡ȋ‹‡œ‡”‘Ȍ™‹–Š‹ʹɐȋʹȗ
    ͲǤͳͲͺȌ™ƒ•ͻͷǤ͵Ǧͻ͸Ǥ͵Ψǡ™Š‹ Š†‡‘•–”ƒ–‡–Šƒ––Š‡”‡™ƒ•‘’”‡ˆ‡”‡–‹ƒŽ†”‘’Ǧ‘—–‘ˆ”‡Žƒ–‹˜‡‡š‘Ǧ
    Ž‡˜‡Ž ‘˜‡”ƒ‰‡‡š ‡‡†‹‰‡š’‡ –‡†Ž‡˜‡Ž•†—‡–‘”ƒ†‘˜ƒ”‹ƒ–‹‘ǡƒ†–Š‡‡–‹”‡’ƒ‡Ž™ƒ• ‘˜‡”‡†
    ‘•‹•–‡–Ž›„‡–™‡‡”‡ˆ‡”‡ ‡ƒ†‹–‡”ˆ‡”‹‰•—„•–ƒ ‡ ‘†‹–‹‘•Ǥ
    •™‡”‡ƒŽ•‘ ƒŽ —Žƒ–‡†ˆ‘”–Š‡•ƒ†‹†‡Ž•‹–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡ǣͳͲ•ƒ†͸‹†‡Ž•ǤŽŽ
    ‘†‹–‹‘••Š‘™‡†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ–‘ˆͺ͹ǤͷΨǦͻ͵ǤͺΨǤƒ„‘˜‡‘™ƒ•ͳͲͲǤͲΨˆ‘”ƒŽŽ
    ‘†‹–‹‘•ǤŠ‡†ƒ–ƒ‹†‹ ƒ–‡ƒ ‡’–ƒ„Ž‡•‡•‹–‹˜‹–›ƒ†•’‡ ‹ˆ‹ ‹–›™Š‡—•‹‰•ƒ’Ž‡•ƒ ”‘••–Š‡
    •–‘”ƒ‰‡ ‘†‹–‹‘•Ǥ
    Š‡’ƒ‡ŽǦ™‹†‡•™‡”‡ƒŽ•‘ ƒŽ —Žƒ–‡†ˆ‘”•ƒ†‹†‡Ž•™‹–Š‹–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡™‹–Š‹ͷͷ
    ‰‡‡•ǡ•ƒ†ˆ—•‹‘•ǤŠ‡–‘–ƒŽ•‡–‘ˆ‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•™ƒ••‡––‘–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡‡š Ž—†‹‰
    ˜ƒ”‹ƒ–•ˆ‘—†–‘„‡’‘•‹–‹˜‡‹–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǤŠ‡†‹• ‘”†ƒ–‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•™‡”‡
    †‡ˆ‹‡†ƒ•–Š‘•‡‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•–Šƒ–™‡”‡’‘•‹–‹˜‡‹–Š‡‘Ǧ”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǤŠ‡’ƒ‡Ž™‹†‡
    ™ƒ•ͻͻǤͻΨˆ‘” ‘†‹–‹‘ͳȋ͹͵ͻǡͷͷͲ‘—–‘ˆ͹͵ͻǡͷͷʹ˜ƒ”‹ƒ–•ȌǡͻͻǤͻΨȋ͹͵ͻǡͷͷͲ‘—–‘ˆ͹͵ͻǡͷͷʹ
    ˜ƒ”‹ƒ–•Ȍˆ‘” ‘†‹–‹‘ʹǡƒ†ͻͻǤͻΨȋ͹͵ͻǡͷͶͺ‘—–‘ˆ͹͵ͻǡͷͷʹ˜ƒ”‹ƒ–•Ȍˆ‘” ‘†‹–‹‘͵Ǥ
    Š‡™Š‘Ž‡„Ž‘‘†•–ƒ„‹Ž‹–›•–—†›†‡• ”‹„‡†ƒ„‘˜‡™ƒ••—’’Ž‡‡–‡†„›ƒƒ††‹–‹‘ƒŽ•–—†›™‹–Š–™‘
    ‘„Œ‡ –‹˜‡•ǣȋͳȌ–‘†‡‘•–”ƒ–‡–Š‡ ‘ ‘”†ƒ ‡„‡–™‡‡•ƒ’Ž‡•’”‘ ‡••‡†‹–‘’Žƒ•ƒ‘–Š‡•ƒ‡
    †ƒ›ƒ•„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†–Š‡•ƒ’Ž‡•’”‘ ‡••‡†‹–‘’Žƒ•ƒ–Š‡†ƒ›ƒˆ–‡” ‘ŽŽ‡ –‹‘ǢȋʹȌ”‘„—•–‡••
    –‘ Šƒ‰‡•‹”‡Žƒ–‹˜‡Š—‹†‹–›ȋ Ȍ–Šƒ––—„‡•ƒ›„‡‡š’‘•‡†–‘†—”‹‰•Š‹’’‹‰Ǥ
    –‘–ƒŽ‘ˆˆ‘—”•™‡”‡†”ƒ™ˆ”‘‡ƒ Š‘ˆͳͻŠ‡ƒŽ–Š›†‘‘”•Ǥ ‘”‡ƒ Š†‘‘”ǡ‘‡™ƒ•
    ’”‘ ‡••‡†–‘’Žƒ•ƒ™‹–Š‹ͶŠ‘—”•ƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†•Š‹’’‡†–‘ —ƒ”†ƒ– ‡ƒŽ–Š‘†”›‹ ‡
    ‘–Š‡•ƒ‡†ƒ›ǤŠ‹••‡”˜‡†ƒ•–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǤŠ‡‘–Š‡”͵•™‹ŽŽ„‡•—„Œ‡ –‡†–‘
    ‘†‹–‹‘•†‡• ”‹„‡†„‡Ž‘™ǣ
    x ‡•– ‘†‹–‹‘ͳǣ –ƒ –™Š‘Ž‡„Ž‘‘†‹•’ƒ ‡†‹•™ƒ••Š‹’’‡†‘˜‡”‹‰Š––‘
    —ƒ”†ƒ– ‡ƒŽ–Šƒ†’Žƒ•ƒ‹•‘Žƒ–‹‘™ƒ•†‘‡‘–Š‡†ƒ›‘ˆ”‡ ‡‹’–ȋƒ›ͳƒˆ–‡”„Ž‘‘†
    ‘ŽŽ‡ –‹‘ȌǤ
    x ‡•– ‘†‹–‹‘ʹǣš’‘•—”‡‘ˆ™Š‘Ž‡„Ž‘‘†‹•–ƒ”–‹‰‘–Š‡†ƒ›‘ˆ„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†
    ˆ‘”ͳ†ƒ›–‘Ž‘™Š—‹†‹–›ȋʹͷΨ ǡƒ–ʹ͵ιȌ•–‘”ƒ‰‡’”‘ˆ‹Ž‡ǡˆ‘ŽŽ‘™‡†„›•–‘”ƒ‰‡ƒ–‘‘
    –‡’‡”ƒ–—”‡ˆ‘”ͳ†ƒ›ǤŽƒ•ƒ‹•‘Žƒ–‹‘‘ —””‡†‘ƒ›ʹƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘Ǥ
    x ‡•– ‘†‹–‹‘͵ǣ–‘”ƒ‰‡‘ˆ™Š‘Ž‡„Ž‘‘†‹•–ƒ”–‹‰‘–Š‡†ƒ›‘ˆ„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†ˆ‘”
    ͳ†ƒ›ƒ–‘‘–‡’‡”ƒ–—”‡ǡˆ‘ŽŽ‘™‡†„›‡š’‘•—”‡–‘Š‹‰ŠǦŠ—‹†‹–›ȋͻͲΨ ǡƒ–ʹ͵ι •–‘”ƒ‰‡
    ’”‘ˆ‹Ž‡ˆ‘”ͳ†ƒ›ǤŽƒ•ƒ‹•‘Žƒ–‹‘‘ —””‡†‘ƒ›ʹƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘Ǥ
    —–‘ˆ͹͸•ƒ’Ž‡•’”‘ ‡••‡†ǡʹͶ•–—†›•ƒ’Ž‡•ȋ͸†‹•–‹ –†‘‘”•ƒ’Ž‡•ˆ‘”ƒŽŽͶ ‘†‹–‹‘•ȌŠƒ†
    ˆ—†‡”Ž‘ƒ†‹‰‹•‘‡•ƒ’Ž‡•ƒ†‘˜‡”Ž‘ƒ†‹‰‹•‘‡‘–Š‡”•ƒ’Ž‡•†—‡–‘ƒ —ƒ”†ƒ–
    ‘’‡”ƒ–‘”‡””‘”Ǥˆ–‡” Š‡ ǡͷʹ•ƒ’Ž‡•ˆ”‘ͳ͵†‘‘”•’ƒ••‡†ƒŽŽ•ƒ’Ž‡‡–”‹ •ƒ†™‡”‡
    ‹ Ž—†‡†‹–Š‡ƒƒŽ›•‹•Ǥ‡ ‘˜‡”›‘ˆ—‹“—‡‘Ž‡ —Ž‡•ƒ ”‘••–Š‡͵ ‘†‹–‹‘•†‹†‘–•Š‘™ƒ
    ‡‰ƒ–‹˜‡‹’ƒ –‘ˆƒ›ͳ’”‘ ‡••‹‰ƒ†‡š’‘•—”‡‘ˆ–—„‡•–‘Š‹‰ŠȋͻͲΨ Ȍƒ†Ž‘™ȋʹͷΨ Ȍ
    ”‡Žƒ–‹˜‡Š—‹†‹–› ‘†‹–‹‘•Ǥ ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹•–‘”ƒ‰‡ ‘†‹–‹‘‘˜‡””‡ˆ‡”‡ ‡

    ʹͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‘†‹–‹‘”ƒ‰‡†ˆ”‘ͲǤͻͷ–‘ͲǤͻͻǤ ‘”–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡‘ˆ–Š‡†‡˜‹ ‡ǡ–Š‡ˆ”ƒ –‹‘‘ˆ‡š‘•™‹–Š
    ”‡Žƒ–‹˜‡ ‘˜‡”ƒ‰‡™‹–Š‹ʹɐȋʹȗͲǤͳͲͺȌ”ƒ‰‡†ͻͺǤͳȂͻͻǤͲΨǤ
    ƒ•‡†‘–Š‡‡˜‹†‡ ‡ˆ”‘’”‡•‡”˜ƒ–‹‘‘ˆ‘˜‡”ƒŽŽ ‘˜‡”ƒ‰‡ƒ†”‡Žƒ–‹˜‡‡š‘ ‘˜‡”ƒ‰‡–Š‡“—ƒ–‹–›
    ƒ†“—ƒŽ‹–›‘ˆ ˆƒ”‡‘–‹’ƒ –‡†„›ǣȋͳȌ™Š‘Ž‡„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ–˜‡†‘”•‹–‡ƒ†‘˜‡”‹‰Š–
    •Š‹’’‹‰–‘ —ƒ”†ƒ– ‡ƒŽ–Šƒ–”‘‘–‡’‡”ƒ–—”‡ǡˆ‘ŽŽ‘™‡†„›•–ƒ†ƒ”†’Žƒ•ƒ‹•‘Žƒ–‹‘‘†ƒ›ͳ
    ƒˆ–‡” ‘ŽŽ‡ –‹‘ǡ ʹȌ ‡š’‘•—”‡‘ˆ™Š‘Ž‡„Ž‘‘†‹•–ƒ”–‹‰‘–Š‡†ƒ›‘ˆ„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†ˆ‘”ͳ
    †ƒ›–‘Ž‘™”‡Žƒ–‹˜‡Š—‹†‹–›ȋʹͷΨ ǡƒ–ʹ͵ιȌ•–‘”ƒ‰‡’”‘ˆ‹Ž‡ǡˆ‘ŽŽ‘™‡†„›•–‘”ƒ‰‡ƒ–‘‘
    –‡’‡”ƒ–—”‡ˆ‘”ͳ†ƒ›ƒ†’Žƒ•ƒ‹•‘Žƒ–‹‘‘ƒ›ʹƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘ǡƒ†ȋ͵Ȍ–‘”ƒ‰‡‘ˆ™Š‘Ž‡
    „Ž‘‘†‹•–ƒ”–‹‰‘–Š‡†ƒ›‘ˆ„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†ˆ‘”ͳ†ƒ›ƒ–‘‘–‡’‡”ƒ–—”‡ǡˆ‘ŽŽ‘™‡†„›
    ‡š’‘•—”‡–‘Š‹‰Š”‡Žƒ–‹˜‡Š—‹†‹–›ȋͻͲΨ ǡƒ–ʹ͵ιȌ•–‘”ƒ‰‡’”‘ˆ‹Ž‡ˆ‘”ͳ†ƒ›ƒ†’Žƒ•ƒ‹•‘Žƒ–‹‘
    ‘ƒ›ʹƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘Ǥ
    ƒ††‹–‹‘ƒŽ•–—†›™ƒ• ‘†— –‡†™‹–Š™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡• ‘ŽŽ‡ –‡†‹ˆ‘—”•ˆ”‘ͳͳ„”‡ƒ•–
    ƒ ‡”’ƒ–‹‡–••—„Œ‡ –‡†–‘–Š‡•ƒ‡”‡ˆ‡”‡ ‡ǡ•—‡”’”‘ˆ‹Ž‡ǡ™‹–‡”’”‘ˆ‹Ž‡ǡƒ†”‘‘
    –‡’‡”ƒ–—”‡ ‘†‹–‹‘•†‡• ”‹„‡†ƒ„‘˜‡ǡƒ†’Žƒ•ƒ™ƒ•‹•‘Žƒ–‡†‘–Š‡‡‹‰Š–Š†ƒ›Ǥ –‘–ƒŽǡͶ͵‘—–‘ˆ
    ͶͶ•ƒ’Ž‡•’ƒ••‡†ƒŽŽ•‡“—‡ ‹‰‡–”‹ •ǤŽŽͶ•ƒ’Ž‡•ˆ”‘‘‡’ƒ–‹‡–™‡”‡‡š Ž—†‡†ˆ”‘
    ƒƒŽ›•‹•†—‡–‘–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘‘– ‘–ƒ‹‹‰•—ˆˆ‹ ‹‡– ˆ‹’—–Ǥˆ–‡””‡‘˜‹‰–Š‡•‡
    •ƒ’Ž‡•ǡƒ–‘–ƒŽ‘ˆͳͲ’ƒ–‹‡–‰”‘—’•™‡”‡‡˜ƒŽ—ƒ„Ž‡ˆ‘”–Š‡™‹–‡”ƒ†”‘‘–‡’‡”ƒ–—”‡•–‘”ƒ‰‡
    ‘†‹–‹‘•ƒ†ͻ’ƒ–‹‡–‰”‘—’•™‡”‡‡˜ƒŽ—ƒ„Ž‡ˆ‘”–Š‡•—‡”•–‘”ƒ‰‡ ‘†‹–‹‘Ǥ
    Š‡ˆ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹•–‘”ƒ‰‡ ‘†‹–‹‘‘˜‡”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘‘”–‹‡œ‡”‘”ƒ‰‡†
    „‡–™‡‡ͲǤͺ͹ƒ†ͳǤͲͲǤŠ‡ͻͲΨ–™‘Ǧ•‹†‡†Ž‘’’‡”Ǧ‡ƒ”•‘‡šƒ –„‹‘‹ƒŽŽ‘™‡” ‘ˆ‹†‡ ‡Ž‹‹–
    ˆ‘”–Š‡ˆ”ƒ –‹‘‘ˆ‰‡‘‹ –ƒ”‰‡–‡†‡š‘‹ ”‡‰‹‘•™‹–Š”‡Žƒ–‹˜‡‡š‘ǦŽ‡˜‡Ž™‹–Š‹ʹɐ‘ˆ–Šƒ–ˆ‘”
    –Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǡ™Š‡”‡ɐαͲǤʹͲͶǡ”ƒ‰‡†ˆ”‘ͻͺǤ͵Ψ–‘ͻͺǤ͹ΨǤŠ‡•‡†ƒ–ƒ‹†‹ ƒ–‡–Šƒ–
    ™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡• ‘ŽŽ‡ –‡†ˆ”‘„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•ƒ”‡•–ƒ„Ž‡—†‡”–Š‡•Š‹’’‹‰ƒ†•–‘”ƒ‰‡
    ‘†‹–‹‘•–‡•–‡†Ǥ
    ƒ•‡†‘–Š‡•‡•–—†›”‡•—Ž–•ǡ™Š‘Ž‡„Ž‘‘†ƒ›„‡•–‘”‡†‹‡ŽŽǦ ”‡‡•–—„‡•ˆ‘”—’–‘͹†ƒ›•
    ƒˆ–‡”„Ž‘‘† ‘ŽŽ‡ –‹‘ƒ†’”‹‘”–‘’Žƒ•ƒ‹•‘Žƒ–‹‘ƒ† ƒ™‹–Š•–ƒ†™‹–‡”ƒ†•—‡”•Š‹’’‹‰
    ‘†‹–‹‘•Ǥ

    c. Plasma Stability
    ‘†‡ˆ‹‡–Š‡•–‘”ƒ‰‡ ‘†‹–‹‘•ƒ†‡˜ƒŽ—ƒ–‡–Š‡•–ƒ„‹Ž‹–›‘ˆ’Žƒ•ƒ‹•‘Žƒ–‡†ˆ”‘™Š‘Ž‡„Ž‘‘†ǡ
    •–ƒ„‹Ž‹–›ƒ–†‡ˆ‹‡†–‡’‡”ƒ–—”‡•ƒ††—”ƒ–‹‘•™ƒ•ƒ••‡••‡†Ǥƒ’Ž‡•™‡”‡’”‘ ‡••‡†ƒ†”—‘
    —ƒ”†ƒ–͵͸Ͳš‹‡†‹ƒ–‡Ž›ƒˆ–‡”’Žƒ•ƒ‹•‘Žƒ–‹‘‘”ƒˆ–‡”•–‘”ƒ‰‡ƒ–ǦͺͲιάͳͲιˆ‘”Ͷ͸†ƒ›•‘”ʹǦ
    ͺιˆ‘”ʹͶŠ‘—”•Ǥ ‘—”•ˆ”‘ͳʹ ƒ ‡”’ƒ–‹‡–•ǡͶͺ•ƒ’Ž‡•‹–‘–ƒŽǡ™‡”‡ ‘ŽŽ‡ –‡†ƒ†”—‘
    —ƒ”†ƒ–͵͸Ͳšǡ™‹–Š’Žƒ•ƒ•–‘”‡†ƒ––Š‡•’‡ ‹ˆ‹‡†•–‘”ƒ‰‡ ‘†‹–‹‘•ǤŽƒ•ƒˆ”‘‘‡™ƒ•
    ’”‘ ‡••‡†–Š”‘—‰Š ˆ‡š–”ƒ –‹‘‘–Š‡•ƒ‡†ƒ›ƒ•ƒ”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǡ’Žƒ•ƒˆ”‘ƒ•‡ ‘†
    ™ƒ••–‘”‡†ƒ–ʹǦͺιˆ‘”ʹͷŠ‘—”•„‡ˆ‘”‡ ˆ‡š–”ƒ –‹‘ȋˆ‘”ƒʹͶǦŠ‘—”•–ƒ„‹Ž‹–› Žƒ‹ƒ–ʹǦͺιǢ
    ‘†‹–‹‘ͳȌǡ’Žƒ•ƒˆ”‘ƒ–Š‹”†™ƒ••–‘”‡†ƒ–ǦͺͲιάͳͲι™‹–Š–™‘ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ˆ‘”Ͷ͸
    †ƒ›•„‡ˆ‘”‡ ˆ‡š–”ƒ –‹‘ȋˆ‘”ƒͶͷǦ†ƒ›•–ƒ„‹Ž‹–› Žƒ‹ƒ–ǦͺͲιάͳͲιǢ‘†‹–‹‘ʹȌǡƒ†’Žƒ•ƒ
    ˆ”‘ƒˆ‘—”–Š™ƒ••–‘”‡†ƒ–ǦͺͲιάͳͲιˆ‘”‘‡›‡ƒ”„‡ˆ‘”‡ ˆ‡š–”ƒ –‹‘–‘•—’’‘”–—•ƒ‰‡
    ‘ˆ•–‘”‡†’Žƒ•ƒˆ‘”ƒƒŽ›–‹ ƒŽ˜ƒŽ‹†ƒ–‹‘ȋȌ•–—†‹‡•ȋ‘†‹–‹‘͵ȌǤš–”ƒ –‡† ˆˆ”‘‡ƒ Š
    ‘†‹–‹‘™ƒ••–‘”‡†ƒ–ǦʹͲιάͷ闐–‹Žˆ—”–Š‡”’”‘ ‡••‹‰Ǥ
    —–‘ˆͶͺ•ƒ’Ž‡•’”‘ ‡••‡†ǡͶͲ•–—†›•ƒ’Ž‡•ȋͳͳ•ƒ’Ž‡•‹”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǡͺ•ƒ’Ž‡•‹
    ‘†‹–‹‘ͳǡͳͲ•ƒ’Ž‡•‹‘†‹–‹‘ʹƒ†ͳͳ•ƒ’Ž‡•‹‘†‹–‹‘͵Ȍ’ƒ••‡†–Š‡‹””‡•’‡ –‹˜‡‹Ǧ
    ’”‘ ‡••ƒ†’‘•–Ǧ•‡“—‡ ‹‰‡–”‹ •ƒ†Šƒ†ƒ–Ž‡ƒ•–‘‡”‡ˆ‡”‡ ‡Ǧ ‘†‹–‹‘•ƒ’Ž‡’ƒ‹”ǡ–Š—•
    ™‡”‡‹ Ž—†‡†‹–Š‡ˆ‹ƒŽƒƒŽ›•‹•Ǥ –Š‡–Š”‡‡–‡•–‡†•–‘”ƒ‰‡ ‘†‹–‹‘•ǡ•ƒ’Ž‡•†‡‘•–”ƒ–‡†

    ʹ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ƒ ‡’–ƒ„Ž‡’‡”ˆ‘”ƒ ‡Ǥ –Š‡–Š”‡‡–‡•–‡†•–‘”ƒ‰‡ ‘†‹–‹‘•ǡ•ƒ’Ž‡•†‡‘•–”ƒ–‡†ƒ ‡’–ƒ„Ž‡
    •ƒ’Ž‡ǦŽ‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›ǡ”‡Žƒ–‹˜‡‡š‘ǦŽ‡˜‡Ž ‘˜‡”ƒ‰‡ǡƒ†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ ‡Ǥ
    ƒ’Ž‡ǦŽ‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›•Š‘™‡†ˆ‘Ž† Šƒ‰‡‘ˆͲǤͻ͵ǡͳǤͳͲƒ†ͲǤͻͻǤš‘ǦŽ‡˜‡Ž”‡Žƒ–‹˜‡
    ‘˜‡”ƒ‰‡†‡‘•–”ƒ–‡†ͻʹǤͺΨǦͻ͹ǤͳΨˆ”ƒ –‹‘‘ˆ‡š‘•™‹–Š‹ʹɐ‘ˆ‡š’‡ –‡†”‡Žƒ–‹˜‡ ‘˜‡”ƒ‰‡Ǥ
    •™‡”‡ƒŽ•‘ ƒŽ —Žƒ–‡†ˆ‘”–Š‡•ƒ†‹†‡Ž•‹–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡™‹–Š‹ͷͷ‰‡‡•–Šƒ–ƒ”‡
    ”‡’‘”–ƒ„Ž‡„›–‡•–ǡƒ•™‡ŽŽƒ•–Š‡”‡’‘”–ƒ„Ž‡ƒ†ˆ—•‹‘‰‡‡•ǣͳͶ•ǡͳ‹†‡Žƒ†ͳǤŠ”‡‡
    ‘†‹–‹‘••Š‘™‡†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ–‘ˆ͹͸ǤͻΨǦ͹ͺǤ͸ΨǤƒ„‘˜‡‘™ƒ•ͻͲǤͻΨǦͻͳǤ͹Ψ
    ˆ‘”ƒŽŽ ‘†‹–‹‘•ȋƒ•‹‰Ž‡˜ƒ”‹ƒ–™ƒ•†‹• ‘”†ƒ–ȌǤƒ ”‘••–Š‡”‡’‘”–ƒ„Ž‡”ƒ‰‡™ƒ•ͻͻǤͻΨǤ
    ƒ•‡†‘–Š‡•‡•–—†›”‡•—Ž–•ǡ’Žƒ•ƒƒ›„‡•–‘”‡†ƒ–ʹǦͺιˆ‘”ʹͶŠ‘—”•‘”ƒ–ǦͺͲιάͳͲι™‹–Šʹ
    ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ˆ‘”ͳ›‡ƒ”„‡ˆ‘”‡ ˆ‡š–”ƒ –‹‘Ǥ
    ††‹–‹‘ƒŽŽ›ǡ–Š‡•–ƒ„‹Ž‹–›‘ˆ’Žƒ•ƒ‹•‘Žƒ–‡†ˆ”‘„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•™ƒ••–—†‹‡†—•‹‰™Š‘Ž‡
    „Ž‘‘†•’‡ ‹‡• ‘ŽŽ‡ –‡†ˆ”‘ʹʹ†‘‘”•Ǥ ‘”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǡ ˆ™ƒ•‡š–”ƒ –‡†ƒˆ–‡”
    ’Žƒ•ƒ‹•‘Žƒ–‹‘™‹–Š‹ͶͺŠ‘—”•‘ˆ†‡Ž‹˜‡”›Ǥ ‘”–Š‡–‡•–•–‘”ƒ‰‡ ‘†‹–‹‘ǡ’Žƒ•ƒ™ƒ••–‘”‡†ƒ–Ǧ
    ͺͲιάͳͲιˆ‘”tͶͷ†ƒ›•„‡ˆ‘”‡ ˆ‡š–”ƒ –‹‘ǤŽŽͶͶ•ƒ’Ž‡•’ƒ••‡†–Š‡‹””‡•’‡ –‹˜‡‹Ǧ’”‘ ‡••
    ƒ†’‘•–•‡“—‡ ‹‰‡–”‹ •Ž‡ƒ†‹‰–‘ʹʹ‡˜ƒŽ—ƒ„Ž‡•ƒ’Ž‡’ƒ‹”•Ǥ
    Š‡ˆ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹•–‘”ƒ‰‡ ‘†‹–‹‘‘˜‡”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘™ƒ•ͲǤͻͶǤŠ‡ͻͲΨ
    –™‘Ǧ•‹†‡†Ž‘’’‡”Ǧ‡ƒ”•‘‡šƒ –„‹‘‹ƒŽŽ‘™‡” ‘ˆ‹†‡ ‡Ž‹‹–ˆ‘”–Š‡ˆ”ƒ –‹‘‘ˆ‰‡‘‹ –ƒ”‰‡–‡†
    ‡š‘‹ ”‡‰‹‘•™‹–Š”‡Žƒ–‹˜‡‡š‘ǦŽ‡˜‡Ž™‹–Š‹ʹɐ‘ˆ–Šƒ–ˆ‘”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǡ™Š‡”‡ɐα
    ͲǤʹͲͶǡ™ƒ•ͻͺǤͳΨǤƒ†ƒ ”‘••ƒŽŽ”‡ˆ‡”‡ ‡Ǧ’‘•‹–‹˜‡ƒ†”‡ˆ‡”‡ ‡Ǧ‡‰ƒ–‹˜‡’‘•‹–‹‘•ƒ‘‰
    –Š‡’ƒ‹”‡†•ƒ’Ž‡•‹ƒ”‡ˆ‡”‡ ‡Ǧ•–‘”ƒ‰‡ ‘†‹–‹‘™‡”‡ͺͺǤͶΨƒ†ͳͲͲǤͲΨǡ”‡•’‡ –‹˜‡Ž›ǤŠ‡”‡•—Ž–•
    ‘ˆ‹”–Šƒ–•–‘”‹‰’Žƒ•ƒƒ–ǦͺͲιˆ‘”‘˜‡”Ͷͷ†ƒ›•’”‡•‡”˜‡•–Š‡•ƒ’Ž‡“—ƒŽ‹–›‘ˆ„”‡ƒ•– ƒ ‡”
    •ƒ’Ž‡•Ǥ

    d. cfDNA Stability
    ‘†‡ˆ‹‡–Š‡•–‘”ƒ‰‡ ‘†‹–‹‘•ƒ†‡˜ƒŽ—ƒ–‡–Š‡•–ƒ„‹Ž‹–›‘ˆ ˆ‡š–”ƒ –‡†ˆ”‘–Š‡’Žƒ•ƒ‘ˆ
    ™Š‘Ž‡„Ž‘‘†ǡ•–ƒ„‹Ž‹–›ƒ–†‡ˆ‹‡†–‡’‡”ƒ–—”‡•ƒ††—”ƒ–‹‘•™ƒ•ƒ••‡••‡†Ǥ‹‰Š–›Ǧ‡‹‰Š–ȋͺͺȌ•ƒ’Ž‡•
    ™‡”‡ ‘ŽŽ‡ –‡†ˆ”‘ʹʹ’ƒ–‹‡–•ƒ†”—‘ —ƒ”†ƒ–͵͸Ͳšǡ™‹–Š ˆ•–‘”‡†‹–Š‡•’‡ ‹ˆ‹‡†
    •–‘”ƒ‰‡ ‘†‹–‹‘•Ǥƒ’Ž‡•™‡”‡•’Ž‹–‹–‘–™‘‡š–”ƒ –‹‘ƒ”•ȋ™‹–Š“—ƒ–‹ˆ‹ ƒ–‹‘‡‹–Š‡”„‡ˆ‘”‡ǡ‘”
    ƒˆ–‡”ˆ”‡‡œ‹‰Ȍ–‘‡•–ƒ„Ž‹•Š•–ƒ„‹Ž‹–›‘ˆ ˆ—†‡”„‘–Š‡ƒ•—”‡‡–™‘”ˆŽ‘™•Ǥ
    ‹š–›Ǧ•‹šȋ͸͸Ȍ•ƒ’Ž‡•™‡”‡’”‘ ‡••‡†ˆ‘”–Š‡”‡ˆ‡”‡ ‡ƒ†ʹ ‘†‹–‹‘•„‡Ž‘™Ǥ
    x ‡ˆ‡”‡ ‡ ‘†‹–‹‘ǣ‘•–Ǧ‡š–”ƒ –‹‘“—ƒ–‹–ƒ–‹‘ǣ—ƒ–‹–ƒ–‹‘ǡ†‹Ž—–‹‘ǡƒ†Ž‹„”ƒ”›
    ’”‡’ƒ”ƒ–‹‘’‘•–Ǧ‡š–”ƒ –‹‘‘–Š‡•ƒ‡†ƒ›Ǥ
    x ‡ˆ‡”‡ ‡ ‘†‹–‹‘ǣ—ƒ–‹–ƒ–‹‘ǡ†‹Ž—–‹‘ǡƒ†Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘’‘•–Ǧ‡š–”ƒ –‹‘‘–Š‡
    •ƒ‡†ƒ›Ǥ
    x ‘†‹–‹‘ͳǣ—ƒ–‹–ƒ–‹‘ƒ††‹Ž—–‹‘’‘•–Ǧ‡š–”ƒ –‹‘‘–Š‡•ƒ‡†ƒ›ǡˆ‘ŽŽ‘™‡†„›•–‘”ƒ‰‡
    ‘ˆ ˆƒ–ʹǦͺιˆ‘”ʹͷŠ‘—”•ȋ‹ Ž—‹†–—„‡• Ȍ„‡ˆ‘”‡Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘ȋˆ‘”ƒʹͶǦŠ‘—”
    •–ƒ„‹Ž‹–› Žƒ‹ƒ–ʹǦͺι Ǥ
    x ‘†‹–‹‘ͳǣ–‘”ƒ‰‡‘ˆ ˆƒ–ʹǦͺιˆ‘”ʹͷŠ‘—”•ȋ‹‹‘”ƒ†‡Ž—–‹‘’Žƒ–‡Ȍǡˆ‘ŽŽ‘™‡†„›
    “—ƒ–‹–ƒ–‹‘ƒ†Ž‹„”ƒ”›†‹Ž—–‹‘ǡ„‡ˆ‘”‡Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘ȋˆ‘”ƒʹͶǦŠ‘—”•–ƒ„‹Ž‹–› Žƒ‹ƒ–ʹǦ
    ͺιȌǤ
    x ‘†‹–‹‘ʹǣ—ƒ–‹–ƒ–‹‘ƒ††‹Ž—–‹‘’‘•–Ǧ‡š–”ƒ –‹‘‘–Š‡•ƒ‡†ƒ›ǡˆ‘ŽŽ‘™‡†„›•–‘”ƒ‰‡
    ‘ˆ ˆƒ–ǦʹͲιάͷι’Ž—•ʹˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ˆ‘”Ͷ͸†ƒ›•ȋ‹ Ž—‹†–—„‡•Ȍ„‡ˆ‘”‡Ž‹„”ƒ”›
    ’”‡’ƒ”ƒ–‹‘ȋˆ‘”ƒͶͷǦ†ƒ›•–ƒ„‹Ž‹–› Žƒ‹ƒ–ǦʹͲιάͷιȌǤ

    ʹ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    x ‘†‹–‹‘ʹǣ–‘”ƒ‰‡‘ˆ ˆƒ–ǦʹͲιάͷι’Ž—•ʹˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ˆ‘”Ͷ͸†ƒ›•ȋ‹‹‘”ƒ†
    ‡Ž—–‹‘’Žƒ–‡Ȍǡˆ‘ŽŽ‘™‡†„›“—ƒ–‹–ƒ–‹‘ƒ†Ž‹„”ƒ”›†‹Ž—–‹‘ǡ„‡ˆ‘”‡Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘ȋˆ‘”ƒ
    ͶͷǦ†ƒ›•–ƒ„‹Ž‹–› Žƒ‹ƒ–ǦʹͲιάͷιȌǤ
    x ‘†‹–‹‘͵ǣ—ƒ–‹–ƒ–‹‘ƒ††‹Ž—–‹‘’‘•–Ǧ‡š–”ƒ –‹‘‘–Š‡•ƒ‡†ƒ›ǡˆ‘ŽŽ‘™‡†„›•–‘”ƒ‰‡
    ‘ˆ ˆƒ–ǦʹͲιάͷι’Ž—•ͷˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ˆ‘”‘‡›‡ƒ”–‘•—’’‘”–—•ƒ‰‡‘ˆ•–‘”‡†
    ˆˆ‘”•–—†‹‡•‹ Ž—‹†–—„‡•„‡ˆ‘”‡Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘Ǥ
    x ‘†‹–‹‘͵ǣ–‘”ƒ‰‡‘ˆ ˆƒ–ǦʹͲιάͷι’Ž—•ͷˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ˆ‘”‘‡›‡ƒ”–‘
    •—’’‘”–—•ƒ‰‡‘ˆ•–‘”‡† ˆˆ‘”•–—†‹‡•ȋ‹‹‘”ƒ†‡Ž—–‹‘’Žƒ–‡Ȍǡˆ‘ŽŽ‘™‡†„›
    “—ƒ–‹–ƒ–‹‘ƒ†Ž‹„”ƒ”›†‹Ž—–‹‘ǡ„‡ˆ‘”‡Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘Ǥ
    —–‘ˆͺͺ•ƒ’Ž‡•’”‘ ‡••‡†ǡͺ͹•–—†›•ƒ’Ž‡•’ƒ••‡†‡–”‹ •ƒ†™‡”‡‹ Ž—†‡†‹–Š‡ˆ‹ƒŽ
    ƒƒŽ›•‹•Ǥ –Š‡͵–‡•–‡†•–‘”ƒ‰‡ ‘†‹–‹‘•‹„‘–Šƒ”•ǡ•ƒ’Ž‡•†‡‘•–”ƒ–‡†ƒ ‡’–ƒ„Ž‡
    ’‡”ˆ‘”ƒ ‡Ǥ
    Š‡”‡ ‘˜‡”›‘ˆ—‹“—‡‘Ž‡ —Ž‡•ƒ ”‘•••–‘”ƒ‰‡ ‘†‹–‹‘•†‹†‘–•Š‘™ƒ‡‰ƒ–‹˜‡‹’ƒ –‘ˆ
    •–‘”ƒ‰‡ǣˆ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹•–‘”ƒ‰‡ ‘†‹–‹‘‘˜‡””‡ˆ‡”‡ ‡ ‘†‹–‹‘”ƒ‰‡†ˆ”‘ͲǤͻ͵–‘
    ͳǤͲ͸‹ƒ”ȋ“—ƒ–‹–ƒ–‹‘’‘•–Ǧ‡š–”ƒ –‹‘ȌǢƒ†ˆ”‘ͲǤͻͲ–‘ͲǤͻ͸‹ƒ”ȋ“—ƒ–‹–ƒ–‹‘’‘•–Ǧ
    •–‘”ƒ‰‡ȌǤ
    ‡Žƒ–‹˜‡‡š‘ ‘˜‡”ƒ‰‡™ƒ•ƒŽ•‘ ‘’ƒ”‡†ˆ‘”‡ƒ Š‘ˆ–Š‡ͷͲͺ‡š‘”‡‰‹‘•‹ͷͷ‰‡‡•”‡’‘”–‡†„›
    –Š‡–‡•–ǤŠ‡ˆ”ƒ –‹‘‘ˆ‡š‘•™‹–Š”‡Žƒ–‹˜‡‡š‘Ž‡˜‡Ž ‘˜‡”ƒ‰‡†‹ˆˆ‡”‡ ‡„‡–™‡‡ ‘†‹–‹‘ƒ†
    ”‡ˆ‡”‡ ‡™‹–Š‹ʹߪ™ƒ•ͻʹǤ͵Ǧͻ͹Ǥ͵Ψ‹”ǡƒ†ͺ͹ǤͶǦͻ͵ǤͻΨ‹”ǤŠ‡†ƒ–ƒ•Š‘™–Šƒ––Š‡”‡
    ™ƒ•‘’”‡ˆ‡”‡–‹ƒŽ†”‘’‘—–‘ˆ”‡Žƒ–‹˜‡‡š‘ǦŽ‡˜‡Ž ‘˜‡”ƒ‰‡‹‡š ‡••‘ˆ™Šƒ–‹•‡š’‡ –‡††—‡–‘
    ”ƒ†‘˜ƒ”‹ƒ–‹‘ǡƒ†–Š‡’ƒ‡Ž™ƒ• ‘˜‡”‡† ‘•‹•–‡–Ž›„‡–™‡‡”‡ˆ‡”‡ ‡ƒ†•–‘”ƒ‰‡ ‘†‹–‹‘•Ǥ
    •™‡”‡ƒŽ•‘ ƒŽ —Žƒ–‡†ˆ‘”–Š‡•ƒ†‹†‡Ž•ǡi.e.ǡͳʹ•ƒ†͵‹†‡Ž•‹”ǡƒ†ͳͳ•
    ƒ†ʹ‹†‡Ž•‹”ǤŠ”‡‡ ‘†‹–‹‘••Š‘™‡†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ–‘ˆͻ͵Ǥ͵ΨǦͳͲͲΨ‹”
    ƒ†ͻʹǤ͵ΨǦͳͲͲΨ‹”Ǥƒ„‘˜‡‘™‡”‡ƒŽŽͳͲͲΨˆ‘”ƒŽŽ ‘†‹–‹‘•‹”ƒ†”Ǥ
    ‘‰‡–Š‡”ǡ–Š‡•‡”‡•—Ž–•†‡‘•–”ƒ–‡†–Šƒ– ˆ™ƒ••–ƒ„Ž‡ƒ–ǦʹͲιάͷιˆ‘”‘‡›‡ƒ”ƒ†ͷ
    ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ƒ†ʹǦͺιˆ‘”ʹͶŠ‘—”•ǤŠ‡•–ƒ„‹Ž‹–›‘ˆ–Š‡•–‘’’‹‰’‘‹–‹–Š‡™‘”ˆŽ‘™ˆ‘”
    •–‘”ƒ‰‡‘ˆ ˆƒ–ʹǦͺιˆ‘”ʹͶŠ‘—”•’‘•–Ǧ‡š–”ƒ –‹‘’”‡Ǧ“—ƒ–‹ˆ‹ ƒ–‹‘™ƒ•ƒŽ•‘‡•–ƒ„Ž‹•Š‡†Ǥ
    ƒ††‹–‹‘ƒŽ•–—†›™ƒ• ‘†— –‡†–‘†‡‘•–”ƒ–‡–Š‡•ƒ’Ž‡•–ƒ„‹Ž‹–›ˆ‘” ˆ‡š–”ƒ –‡†ˆ”‘
    ’Žƒ•ƒ•’‡ ‹‡•‘ˆ„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•ǤŠ‡•–—†›•ƒ’Ž‡•™‡”‡†‡”‹˜‡†ˆ”‘–Š‡•‡ ‘†’Žƒ•ƒ
    ƒŽ‹“—‘–„‡Ž‘‰‹‰–‘ʹͺ’”‡˜‹‘—•Ž›”‡’‘”–‡†„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•ƒ’Ž‡•Ǥˆ–‡”‡š–”ƒ –‹‘ƒ†
    •‡“—‡ ‹‰‘ˆ–Š‡•‡ ‘†’Žƒ•ƒƒŽ‹“—‘–ǡ–Š‡”‡ƒ– ˆ™ƒ••–‘”‡†ƒ–ʹͲιάͷι’Ž—•ͳ
    ˆ”‡‡œ‡Ȁ–Šƒ™ˆ‘”Ͷ͸†ƒ›•Ǥˆ–‡”•–‘”ƒ‰‡ǡƒ‡“—‹˜ƒŽ‡–‹’—–‘ˆ ˆ™ƒ•’”‘ ‡••‡†–Š”‘—‰Š–Š‡
    —ƒ”†ƒ–͵͸Ͳš™‘”ˆŽ‘™Ǥˆ–‡”•‡“—‡ ‹‰–Š‡•–‘”‡†•ƒ’Ž‡ǡ–Š‡•ƒ’Ž‡ǦŽ‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›ǡ
    ‡š‘ǦŽ‡˜‡Ž‘Ž‡ —Ž‡”‡ ‘˜‡”›ǡƒ†˜ƒ”‹ƒ– ƒŽŽ ‘ ‘”†ƒ ‡™‡”‡ ‘’ƒ”‡†„‡–™‡‡–Š‡‘”‹‰‹ƒŽ
    ȋ”‡ˆ‡”‡ ‡Ȍƒ†•–‘”‡†•ƒ’Ž‡•–‘‡˜ƒŽ—ƒ–‡•–ƒ„‹Ž‹–›Ǥ –‘–ƒŽǡͷͷ‘—–‘ˆͷ͸•ƒ’Ž‡•–‡•–‡†ˆ‘”–Š‡•–—†›
    ’ƒ••‡†ƒŽŽ‡–”‹ •ǡ”‡•—Ž–‹‰‹ʹ͹‡˜ƒŽ—ƒ„Ž‡•ƒ’Ž‡’ƒ‹”•Ǥ
    Š‡ˆ‘Ž† Šƒ‰‡‘ˆ‡†‹ƒ‹•–‘”ƒ‰‡ ‘†‹–‹‘‘˜‡”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘™ƒ•ͳǤͲͷǤŠ‡ͻͷΨ
    –™‘Ǧ•‹†‡†Ž‘’’‡”Ǧ‡ƒ”•‘‡šƒ –„‹‘‹ƒŽŽ‘™‡” ‘ˆ‹†‡ ‡Ž‹‹–ˆ‘”–Š‡ˆ”ƒ –‹‘‘ˆ‰‡‘‹ –ƒ”‰‡–‡†
    ‡š‘‹ ”‡‰‹‘•™‹–Š”‡Žƒ–‹˜‡‡š‘ǦŽ‡˜‡Ž™‹–Š‹ʹɐ‘ˆ–Šƒ–ˆ‘”–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǡ™Š‡”‡ɐα
    ͲǤͳͲͺǡ™ƒ•ͻͲǤ͵ΨǤƒ†ƒ ”‘••ƒŽŽ”‡ˆ‡”‡ ‡Ǧ’‘•‹–‹˜‡ƒ†”‡ˆ‡”‡ ‡Ǧ‡‰ƒ–‹˜‡’‘•‹–‹‘•ƒ‘‰
    –Š‡’ƒ‹”‡†•ƒ’Ž‡•‹ƒ”‡ˆ‡”‡ ‡Ǧ•–‘”ƒ‰‡ ‘†‹–‹‘™‡”‡ͺͻǤ͸Ψƒ†ͳͲͲǤͲΨǡ”‡•’‡ –‹˜‡Ž›ǤŠ‡”‡•—Ž–•
    ‘ˆ‹”–Šƒ–•–‘”‹‰ ˆƒ–ǦʹͲιάͷιˆ‘”‘˜‡”Ͷͷ†ƒ›•’”‡•‡”˜‡•–Š‡•ƒ’Ž‡“—ƒŽ‹–›‘ˆ„”‡ƒ•–
    ƒ ‡”•ƒ’Ž‡•Ǥ

    ʹͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    e. Intermediate Product Stability
    ‘†‡ˆ‹‡–Š‡•–‘”ƒ‰‡ ‘†‹–‹‘•ƒ†‡˜ƒŽ—ƒ–‡–Š‡•–ƒ„‹Ž‹–›‘ˆ‹–‡”‡†‹ƒ–‡’”‘†— –•ǡi.e.ǡŽ‹„”ƒ”›’Žƒ–‡ǡ
    ‡”‹ Š‡†Ž‹„”ƒ”›’Žƒ–‡ǡƒ†•‡“—‡ ‹‰’‘‘Žǡ—•‡†ˆ‘””‡’‡ƒ––‡•–‹‰‹–Š‡ —ƒ”†ƒ–͵͸Ͳš
    ™‘”ˆŽ‘™ǡ•–ƒ„‹Ž‹–›ƒ–†‡ˆ‹‡†–‡’‡”ƒ–—”‡•ƒ††—”ƒ–‹‘•™ƒ•ƒ••‡••‡†Ǥƒ’Ž‡•™‡”‡•–‘”‡†ƒ ”‘••
    ƒŽŽ ‘†‹–‹‘•ȋǦʹͲιάͷιˆ‘”ͳ͵ǡͳͷǡ‘”ʹʹ†ƒ›•Ǣ‘”ʹǦͺιˆ‘”͵ͳŠ‘—”•Ȍ™‹–Šƒƒ††‹–‹‘ƒŽ–Š‹”–›ȋ͵ͲȌ
    •ƒ’Ž‡•‘ˆˆ”‡•Š‹–‡”‡†‹ƒ–‡’”‘†— –ˆ‘””‡ˆ‡”‡ ‡ǤƒŽŽ•ˆ”‘–Š‡•–‘”‡†‹–‡”‡†‹ƒ–‡’”‘†— –™‡”‡
    ‘’ƒ”‡†–‘–Š‡ˆ”‡•Š‹–‡”‡†‹ƒ–‡’”‘†— –ȋi.e.–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ȌǤ
    –‘–ƒŽ‘ˆͻͲ•ƒ’Ž‡• ‘–ƒ‹‹‰–Š‡•ƒ’Ž‡’‘‘Ž•ˆ”‘–Š‡’”‡ ‹•‹‘•–—†›ˆ”‘–Š”‡‡†‹•–‹ – ˆ
    Ž‹‹ ƒŽ•ƒ’Ž‡’‘‘Ž•™‡”‡—•‡†ˆ‘”–Š‡•–—†›Ǥ‹š–›•ƒ’Ž‡•™‡”‡’”‘ ‡••‡†–‘–‡•–Ͷ‹–‡”‡†‹ƒ–‡
    •–ƒ„‹Ž‹–› ‘†‹–‹‘•ȋŽ‹„”ƒ”›’Žƒ–‡ǡ‡”‹ Š‡†Ž‹„”ƒ”›’Žƒ–‡ǡʹͲ’•‡“—‡ ‹‰’‘‘ŽǡʹǤʹ’•‡“—‡ ‹‰
    ’‘‘ŽȌƒ†•–‘”‡†ƒ•†‡• ”‹„‡†‹Table 24Ǥ
    Š‡‹–‡”‡†‹ƒ–‡’”‘†— –•–‡•–‡†ˆ‘”Ž‹„”ƒ”›’Žƒ–‡ƒ†‡”‹ Š‡†Ž‹„”ƒ”›’Žƒ–‡™‡”‡•—„Œ‡ –‡†–‘ʹ
    ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•ǤŠ‡ʹͲ’•‡“—‡ ‹‰’‘‘Ž™ƒ••—„Œ‡ –‡†–‘͵ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ǥ
    ƒ Š ‘†‹–‹‘™ƒ•–‡•–‡†‘͵’‘‘Ž•‹ͷ”‡’Ž‹ ƒ–‡•ȋ͵šͷȌˆ‘”ƒ–‘–ƒŽ‘ˆͳͷ•ƒ’Ž‡•ǤŽŽͶ•ƒ’Ž‡
    ‹–‡”‡†‹ƒ–‡’”‘†— – ‘†‹–‹‘•”‡•—Ž–‡†‹ƒ–‘–ƒŽ‘ˆ͸Ͳ•ƒ’Ž‡•ȋͳͷšͶȌ’ƒ••‹‰Ǥ††‹–‹‘ƒŽŽ›ǡ͵Ͳ
    •ƒ’Ž‡•ˆ”‘–Š‡ʹƒƒŽ›–‹ ƒŽ’”‡ ‹•‹‘„ƒ– Š‡•ȋͳͷšʹȌ™‡”‡—•‡†ƒ•”‡ˆ‡”‡ ‡ˆ‘”–Š‡ƒƒŽ›•‹•‘ˆ–Š‹•
    •–—†›Ǥ

    Table 24. Description of Intermediate Product Storage Conditions


    Intermediate Product Storage Target Storage Claim Stability Testing
    ”‹ Š‡†‹„”ƒ”›Žƒ–‡ ǦʹͲιάͷι ͳͶ†ƒ›•ȋ‹ Ž—†‹‰ʹ –Ž‡ƒ•–ͳͷ†ƒ›•ȋ‹ Ž—†‹‰ʹ
    ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ȍ ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ȍ
    ‹„”ƒ”›Žƒ–‡ ǦʹͲιάͷι ʹͳ†ƒ›•ȋ‹ Ž—†‹‰ʹ –Ž‡ƒ•–ʹʹ†ƒ›•ȋ‹ Ž—†‹‰ʹ
    ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ȍ ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ȍ
    ʹͲ’‘‘Ž ǦʹͲιάͷι ͳʹ†ƒ›•ȋ‹ Ž—†‹‰ʹ –Ž‡ƒ•–ͳ͵†ƒ›•ȋ‹ Ž—†‹‰ʹ
    ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ȍ ˆ”‡‡œ‡Ȁ–Šƒ™ › Ž‡•Ȍ
    ʹǤʹ’‘‘Ž ʹǦͺι ͵ͲŠ‘—”• –Ž‡ƒ•–͵ͳŠ‘—”•

    Š‡—ƒŽ‹–ƒ–‹˜‡‡–‡ –‹‘ƒ–‡ȋȌˆ‘”ƒ•–‘”ƒ‰‡ ‘†‹–‹‘™ƒ• ƒŽ —Žƒ–‡†™Š‹ Š‹•‡“—‹˜ƒŽ‡––‘


    ”‡Žƒ–‹˜‡–‘–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘Ǥ™ƒ•†‡ˆ‹‡†ƒ•–Š‡—„‡”‘ˆ’‘•‹–‹˜‡Ž›†‡–‡ –‡†
    –ƒ”‰‡–‡†˜ƒ”‹ƒ–•–Šƒ–™‡”‡’‘•‹–‹˜‡Ž›†‡–‡ –‡†‹–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ƒ ”‘••‡Ž‹‰‹„Ž‡•ƒ’Ž‡•ȋȌ
    †‹˜‹†‡†„›–Š‡–‘–ƒŽ—„‡”‘ˆ’‘•‹–‹˜‡Ž›†‡–‡ –‡†–ƒ”‰‡–‡†˜ƒ”‹ƒ–•–‡•–‡†ƒ ”‘••‡Ž‹‰‹„Ž‡•ƒ’Ž‡•
    ȋȌǡ‡š’”‡••‡†ƒ•ƒ’‡” ‡–ƒ‰‡ȋͳͲͲȗȀȌǤ”‡Žƒ–‹˜‡–‘”‡ˆ‡”‡ ‡ ‘†‹–‹‘•”ƒ‰‡†ˆ”‘ͻ͹Ǥ͹Ψ
    –‘ͳͲͲΨƒ ”‘••ƒŽŽ•–‘”‡†‹–‡”‡†‹ƒ–‡’”‘†— – ‘†‹–‹‘• ‘’ƒ”‡†–‘”‡ˆ‡”‡ ‡ ‘†‹–‹‘•Ǥ
    ™ƒ• ƒŽ —Žƒ–‡†ˆ”‘ƒŽŽ‡‰ƒ–‹˜‡˜ƒ”‹ƒ–•‹–‡•ƒ ”‘••–Š‡ —ƒ”†ƒ–͵͸Ͳš”‡’‘”–ƒ„Ž‡”ƒ‰‡–Šƒ–ƒ”‡
    ‘–†‡–‡ –‡†‹–Š‡”‡ˆ‡”‡ ‡ ‘†‹–‹‘ǤŠ‡–‘–ƒŽ—„‡”‘ˆ†‹•–‹ –˜ƒ”‹ƒ–•‹–Š‡ˆ‹ƒŽ”‡’‘”–ƒ„Ž‡
    ”ƒ‰‡‹•Ͷ͸ǡʹʹ͵”‡’”‡•‡–‹‰Ͷ͸ǡʹͳ͹•ƒ†‹†‡Ž•ǡʹ•ƒ†Ͷˆ—•‹‘•Ǥ ”‘–Š‹•Ž‹•–ǡƒŽŽ ƒŽŽ‡†
    ˜ƒ”‹ƒ–•‹•–—†›•ƒ’Ž‡•ˆ‘”‡ƒ Š‘ˆ–Š‡͵’‘‘Ž•™‡”‡”‡‘˜‡†ƒ•‡š’‡ –‡†’‘•‹–‹˜‡•‹–‡•ˆ‘”
    ”‡’Ž‹ ƒ–‡•‘ˆ–Š‡•ƒ‡’‘‘Ž‹–Š‡”‡ƒ‹‹‰•–—†› ‘†‹–‹‘•Ǥ™ƒ•‰”‡ƒ–‡”–ŠƒͻͻǤͻΨǤ
    ƒ•‡†‘–Š‡•‡•–—†›”‡•—Ž–•ǡ‹–‡”‡†‹ƒ–‡’”‘†— –•ƒ›„‡•–‘”‡†ƒ–ǦʹͲιάͷιˆ‘”ͳͶ†ƒ›•
    ȋ‡”‹ Š‡†Ž‹„”ƒ”›’Žƒ–‡Ȍǡʹͳ†ƒ›•ȋŽ‹„”ƒ”›’Žƒ–‡Ȍǡ‘”ͳʹ†ƒ›•ȋʹͲ’‘‘ŽȌǤ††‹–‹‘ƒŽŽ›ǡ–Š‡ʹǤʹ’’‘‘Ž
    ‹–‡”‡†‹ƒ–‡’”‘†— –ƒ›„‡•–‘”‡†ƒ–ʹǦͺιˆ‘”͵ͲŠ‘—”•Ǥ

    ʹͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ͸ǤͳͲǤ ‡‡”ƒŽƒ„“—‹’‡–ƒ†‡ƒ‰‡–˜ƒŽ—ƒ–‹‘

    a. cfDNA Extraction
    Š‡’‡”ˆ‘”ƒ ‡‘ˆ–Š‡ ˆ‡š–”ƒ –‹‘ˆ”‘’Žƒ•ƒ•ƒ’Ž‡•™ƒ•‡˜ƒŽ—ƒ–‡†‘–Š‡ •›’Š‘›
    ›•–‡Ǥ”‡–”‘•’‡ –‹˜‡ƒƒŽ›•‹•‘ˆ Ž‹‹ ƒŽ™Š‘Ž‡„Ž‘‘†•ƒ’Ž‡•’”‘ ‡••‡†‘–Š‡ —ƒ”†ƒ–͵͸Ͳ
    ‹’Ž‡‡–ƒ–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš†‡˜‹ ‡•›•–‡ȋαͳͳǡʹ͸͹’”‘ ‡••‡†•ƒ’Ž‡•ƒ ”‘••͹ͻ
    ƒ ‡”–›’‡•Ȍǡ‹ Ž—†‹‰•‡ ‘†–—„‡•”‡Ǧ’”‘ ‡••‡†ˆ‘”ƒ“—ƒŽ‹–›ˆƒ‹Ž—”‡‘ˆ–Š‡ˆ‹”•––—„‡‘” Ž‹‹ ƒŽ
    ‡‡†™‡”‡‡˜ƒŽ—ƒ–‡†–‘ Šƒ”ƒ –‡”‹œ‡–Š‡˜ƒ”‹ƒ„‹Ž‹–›„‡–™‡‡‹•–”—‡–•ƒ•™‡ŽŽƒ•–Š‡˜ƒ”‹ƒ„‹Ž‹–›
    „‡–™‡‡”—•‘–Š‡•ƒ‡‹•–”—‡–ǤŠ‡˜ƒ”‹ƒ–‹‘‹ •›’Š‘›‹•–”—‡–ƒ†Ȁ‘””‡ƒ‰‡–Ž‘–
    ‡š’Žƒ‹‡†δʹǤͳΨ‘ˆ˜ƒ”‹ƒ ‡‹ ˆ‡š–”ƒ –‹‘›‹‡Ž†Ǥƒ Š ‘„‹ƒ–‹‘‘ˆ •›’Š‘›”‡ƒ‰‡–
    ‹–•ȋαͶȌȀ‹•–”—‡–•ȋα͹Ȍ”‡•—Ž–‡†‹•— ‡••ˆ—Ž‡š–”ƒ –‹‘‘ˆηͷ‰ ˆƒ–ƒ”ƒ–‡ηͻͶΨǡ™‹–Š
    ƒ–‘–ƒŽ•— ‡••”ƒ–‡‘ˆͻ͹Ǥ͵ΨǤ

    b. Other Instruments and Reagents


    Š‡‘–Š‡”‰‡‡”ƒŽŽƒ„‹•–”—‡–Ȁ”‡ƒ‰‡–•›•–‡•ȋͶʹͲͲƒ’‡–ƒ–‹‘ǡ‹ ”‘Žƒ„ǡ‹ ”‘Žƒ„
    Ž‡–ǡ‡š–‡“ͷͷͲ‡“—‡ ‡”ǡƒ†‡”‹–‹ͻ͸Ǧ‡ŽŽŠ‡”ƒŽ› Ž‡”Ȍ™‡”‡ƒ••‡••‡†‹ ‘„‹ƒ–‹‘‹
    –Š‡’”‡ ‹•‹‘•–—†›Ǥ •–”—‡–•ƒ†”‡ƒ‰‡–•˜ƒ”‹‡†‹͵’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ǤŠ”‡‡•ƒ’Ž‡’‘‘Ž•
    ™‡”‡ ”‡ƒ–‡†ƒ–ͷ‰ ˆ‹’—–•Ǥ‡”‡’Ž‹ ƒ–‡•’‡”’‘‘Ž™‡”‡–‡•–‡†ˆ‘”‡ƒ Š‘ˆ–Š”‡‡’”‡ ‹•‹‘
    ‘„‹ƒ–‹‘•ˆ‘”ƒ–‘–ƒŽ‘ˆ͸„ƒ– Š‡••‡“—‡ ‡†‘ͳʹˆŽ‘™ ‡ŽŽ•ǤŽŽͻͲ•–—†›•ƒ’Ž‡•’ƒ••‡†
    ”‡•’‡ –‹˜‡‡–”‹ •ƒ†™‡”‡‹ Ž—†‡†‹–Š‡ˆ‹ƒŽƒƒŽ›•‹•Ǥ
     ‡’–ƒ„Ž‡ƒŽ–‡”ƒ–‹‘ƒ†”‡•—Ž–•™‡”‡†‡‘•–”ƒ–‡†ƒ ”‘••‹•–”—‡–•ȋ Table 25 Ǥ
     ‡’–ƒ„Ž‡•‡“—‡ ‹‰’ƒ”ƒ‡–‡”•™‡”‡†‡‘•–”ƒ–‡†ƒ ”‘••’”‡ ‹•‹‘ ‘„‹ƒ–‹‘•ȋ Table 26 Ǥ

    Table 25. Sequencer PPA and NPA across Precision Combinations


    Instrument # PPA 95% CI NPA 95% CI
    ͳ ͻͺǤͳΨȋʹͳͲȀʹͳͶȌ ȏͻͷǤ͵ΨǡͻͻǤͷΨȐ ͳͲͲΨȋͶͲȀͶͲȌ ȏͻͳǤʹΨǡͳͲͲΨȐ
    ʹ ͻͺǤͳΨȋͷʹȀͷ͵Ȍ ȏͺͻǤͻΨǡͳͲͲΨȐ ͳͲͲΨȋͳͲȀͳͲȌ ȏ͸ͻǤʹΨǡͳͲͲΨȐ
    ͵ ͻͺǤͳΨȋͳͷ͸ȀͳͷͻȌ ȏͻͶǤ͸ΨǡͻͻǤ͸ΨȐ ͳͲͲΨȋ͵ͲȀ͵ͲȌ ȏͺͺǤͶΨǡͳͲͲΨȐ
    Ͷ ͻ͸Ǥ͵ΨȋͷʹȀͷͶȌ ȏͺ͹Ǥ͵ΨǡͻͻǤͷΨȐ ͳͲͲΨȋͳͲȀͳͲȌ ȏ͸ͻǤʹΨǡͳͲͲΨȐ

    Table 26. Sequencing Flowcell Level QC Parameters across Precision Combinations


    QC Parameters (threshold) Mean SD CV%
    Ž—•–‡”‡•‹–›ȋηͳ͹ͲͲͲͲǡζʹͺͲͲͲͲȌ ʹʹ͵ǡ͵͵͵ ͻ͸ͳͲ ͶǤ͵
    ‡” ‡–ƒ‰‡‘ˆŽ—•–‡”•ƒ••‹‰ ‹Ž–‡”ȋη͹ͲǤͲȌ ͺͻǤͳ ͳǤʹ ͳǤ͵
    —ƒŽ‹–› ‘”‡ȋ͵ͲȌ‹”‡ƒ†ͳȋη͹ͲǤͲȌ ͺͻǤͳ ͲǤ͹ ͲǤͺ
    —ƒŽ‹–› ‘”‡ȋ͵ͲȌ‹”‡ƒ†ʹȋη͹ͲǤͲȌ ͺ͹ǤͲ ͲǤͺ ͲǤͻ
    —ƒŽ‹–› ‘”‡ȋ͵ͲȌ‹‹†‡šȋη͹ͲǤͲȌ ͻͷǤ͵ ͲǤͶ ͲǤͷ
    ”‡’Šƒ•‹‰‹†‡šȋζͲǤͲͳȌ Ͳ Ͳ Ȁ
    ”‡’Šƒ•‹‰ͳȋζͲǤͲͳȌ ͲǤͲͲͳʹ ͲǤͲͲͲͲͺ ͸Ǥͻ
    ”‡’Šƒ•‹‰ʹȋζͲǤͲͳȌ ͲǤͲͲͳͶ ͲǤͲͲͲͲͷ ͵Ǥͺ
    Šƒ•‹‰‹†‡šȋζͲǤͲͳȌ Ͳ Ͳ Ȁ
    Šƒ•‹‰ͳȋζͲǤͲͳȌ ͲǤͲͲͳͶ ͲǤͲͲͲʹʹ ͳͶǤͻ
    Šƒ•‹‰ʹȋζͲǤͲͳȌ ͲǤͲͲͳ͹ ͲǤͲͲͲͳͺ ͳͲǤͷ

     ‘ Ž—•‹‘ǡ–Š‡ ”‹–‹ ƒŽ‰‡‡”ƒŽŽƒ„‹•–”—‡–•ƒ†”‡ƒ‰‡–•†‡‘•–”ƒ–‡†ƒ ‡’–ƒ„Ž‡


    ’‡”ˆ‘”ƒ ‡ˆ‘”—•‡™‹–Š —ƒ”†ƒ–͵͸ͲšǤ

    ͵Ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ͸ǤͳͳǤ ƒǦƒ ‡”ƒŽ›•‹•
    —ƒ”†ƒ–͵͸Ͳš’‡”ˆ‘”ƒ ‡ Šƒ”ƒ –‡”‹•–‹ •™‡”‡‡•–ƒ„Ž‹•Š‡†—•‹‰ ˆ†‡”‹˜‡†ˆ”‘ƒ™‹†‡
    ”ƒ‰‡‘ˆ ƒ ‡”–›’‡•Ǥ –‘–ƒŽǡͻʹͻ’ƒ–‹‡–•ƒ’Ž‡•”‡’”‡•‡–‹‰ʹͲ ƒ ‡” ƒ–‡‰‘”‹‡•™‡”‡‹ Ž—†‡†
    ƒ ”‘••–Š‡ƒƒŽ›–‹ ƒŽ˜ƒŽ‹†ƒ–‹‘•–—†‹‡•’‡”ˆ‘”‡†ˆ‘” —ƒ”†ƒ–͵͸ͲšǤ
    ˆˆ”ƒ‰‡–•‹œ‡†‹•–”‹„—–‹‘•™‡”‡ ‘’ƒ”‡†ƒ ”‘•••ƒ’Ž‡•ˆ”‘—Ž–‹’Ž‡ ƒ ‡”–›’‡•Ǥ ‘”–Š‹•
    ƒƒŽ›•‹•ǡ Ž‹‹ ƒŽ•ƒ’Ž‡•™‡”‡•‡Ž‡ –‡†ˆ”‘ƒƒŽ›–‹ ƒŽ˜ƒŽ‹†ƒ–‹‘•–—†‹‡•”‡’”‡•‡–‹‰ͺ†‹ˆˆ‡”‡–
    ƒ ‡”–›’‡•ǣǡ„”‡ƒ•–ǡ ‘Ž‘”‡ –ƒŽ ƒ ‡”ȋȌǡ’”‘•–ƒ–‡ǡƒ†—–‡”‹‡ǤŠ‡‡Ž‡ –”‘’Š‡”‘‰”ƒ•‘ˆ
    ˆ’‘•–Ǧ‡š–”ƒ –‹‘ˆ”‘’Žƒ•ƒ‘–Š‡ƒ’‡–ƒ–‹‘•Š‘™ƒ‘‘Ǧ— Ž‡‘•‘ƒŽ’‡ƒ–Šƒ–‹•
    ‘•‹•–‡–ƒ ”‘•• ƒ ‡”–›’‡•ƒ†™‹–Š’—„Ž‹•Š‡†Ž‹–‡”ƒ–—”‡Ǥƒ•‡†‘–Š‡•‡‘„•‡”˜ƒ–‹‘•ǡ ˆ
    ˆ”ƒ‰‡–•‹œ‡†‹•–”‹„—–‹‘•ƒ”‡•‹‹Žƒ”ƒ ”‘•• ƒ ‡”–›’‡•ƒ†™‘—Ž†‰‡‡”ƒ–‡“—ƒŽ‹–ƒ–‹˜‡Ž›•‹‹Žƒ”
    ‹’—–•‹–‘–Š‡ƒ••ƒ›™‘”ˆŽ‘™Ǥ
    ‘ˆ—”–Š‡”—†‡”•–ƒ†–Š‡’‡”ˆ‘”ƒ ‡‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ ”‘•• ƒ ‡”–›’‡•ǡ’”‡Ǧ•‡“—‡ ‹‰
    “—ƒŽ‹–›‡–”‹ •ȋ ˆ‡š–”ƒ –‹‘ƒ†Ž‹„”ƒ”›‡”‹ Š‡–Ȍǡ’‘•–Ǧ•‡“—‡ ‹‰“—ƒŽ‹–›‡–”‹ •ȋ‘Ǧ
    •‹‰Ž‡–‘ ‘˜‡”ƒ‰‡ǡ‹Ǧ’”‘ ‡•• ‘–ƒ‹ƒ–‹‘ǡ ‘˜‡”ƒ‰‡‡š ‡’–‹‘•ǡ „‹ƒ•ǡƒ†‘–ƒ”‰‡–”ƒ–‡Ȍǡƒ•
    ™‡ŽŽƒ•–Š‡ Ž‹‹ ƒŽŽ›”‡Ž‡˜ƒ–‡–”‹ •‘ˆ‘˜‡”ƒŽŽ•— ‡••”ƒ–‡ƒ††‡–‡ –ƒ„Ž‡Ž‡˜‡Ž•‘ˆ–—‘”
    •Š‡††‹‰ȋƒ•‡ƒ•—”‡†„›–Š‡ƒš‹—ƒŽŽ‡Ž‹ ˆ”ƒ –‹‘‘ˆ†‡–‡ –‡†•‘ƒ–‹ ˜ƒ”‹ƒ–•Ȍƒ ”‘•••ƒ’Ž‡•
    –‡•–‡†™‹–Š —ƒ”†ƒ–͵͸Ͳš ƒ†‹†ƒ–‡ƒ••ƒ›‹’Ž‡‡–‡†‹ —ƒ”†ƒ–ǯ• Žƒ„‘”ƒ–‘”›ƒ•ƒ
    –‡•–™‡”‡ƒƒŽ›œ‡†ǤŠ‡ —ƒ”†ƒ–͵͸Ͳƒ••ƒ›‹–Š‹•ƒƒŽ›•‹•”‡ˆ‡”•–‘ƒ‹’Ž‡‡–ƒ–‹‘‘ˆ
    –Š‡š—–‹Ž‹œ‹‰–Š‡‡šƒ – ‘ˆ‹‰—”ƒ–‹‘ǤŠ‹•–‡•–Šƒ•„‡‡‘’‡”ƒ–‡†‹–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠŽ‹‹ ƒŽ
    ƒ„‘”ƒ–‘”›–‘’”‘ ‡••‘˜‡”ͳͲǡͲͲͲ Ž‹‹ ƒŽ•ƒ’Ž‡•ǤŠ‡“—ƒŽ‹–›–Š”‡•Š‘Ž†•ƒ”‡‡“—‹˜ƒŽ‡–„‡–™‡‡
    „‘–Š˜‡”•‹‘•™‹–Š–Š‡‡š ‡’–‹‘‘ˆƒƒ††‹–‹‘ƒŽͷ‰‹‹—‹’—–ƒ‘—–”‡“—‹”‡‡–ˆ‘”
    —ƒ”†ƒ–͵͸Ͳšƒ†ƒ—’’‡”Ž‹‹––‘–Š‡ Ž—•–‡”†‡•‹–›’‡”ˆŽ‘™ ‡ŽŽǤŠ‡•‡ƒ††‹–‹‘ƒŽ
    ”‡“—‹”‡‡–•™‡”‡ƒ’’Ž‹‡†”‡–”‘•’‡ –‹˜‡Ž›–‘–Š‡ —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•–‘‹ˆ‡”•— ‡••”ƒ–‡•ˆ‘”
    —ƒ”†ƒ–͵͸Ͳšȋ‘–‡–Šƒ–ƒ•‹‰Ž‡ˆŽ‘™ ‡ŽŽǡ‘—–‘ˆ͸ͶͲǡˆƒ‹Ž•–Š‡—’’‡”Ž‹‹–‘ˆ Ž—•–‡”†‡•‹–›ˆ‘”–Š‡
    —ƒ”†ƒ–͵͸Ͳš Ǥ
    Š‡’ƒǦ ƒ ‡”ƒƒŽ›•‹•‡˜ƒŽ—ƒ–‡†ͳͳǡͲͻ͹•ƒ’Ž‡•’”‘ ‡••‡†ƒ ”‘••ʹ͵ ƒ ‡” ƒ–‡‰‘”‹‡•Ǥ ‘”‡ƒ Š
    ƒ ‡” ƒ–‡‰‘”›ǡ“—ƒŽ‹–›’ƒ••”ƒ–‡•™‡”‡‡ƒ•—”‡†ǡƒ†–Š‡‘˜‡”ƒŽŽ’ƒ–‹‡–•— ‡••”ƒ–‡™ƒ•εͻͺΨˆ‘”
    ƒŽŽ ƒ ‡” ƒ–‡‰‘”‹‡•ǤŠ‡ˆ”‡“—‡ ›‘ˆˆƒ‹Ž—”‡•ˆ‘”‡ƒ Š‘ˆ–Š‡‹†‹˜‹†—ƒŽ‡–”‹ •™ƒ••‹‹Žƒ”ƒ ”‘••
    ƒ ‡”–›’‡•ȋTable 27 Ǥ

    Table 27. Sample Success Rate across 23 Cancers


    Patient Sample
    Sample Preparation QC Sequencing QC Data, %
    Category Data Data, % Pass Pass (median value) Patient Outcome Metrics
    Cancer Category Total First cfDNA Library In Coverage GC Non- On Overall Maximum
    Patients Tube Ex. Enrich. process Exception Bias singleton Target Sample MAF:
    Success Sample Sample Contam- Coverage Rate Pass median
    QC Pass QC Pass ination Rate (standard
    % % % deviation)
    ”‡ƒ•– ͳͷͳ͸ ͻͷǤʹ ͻ͸Ǥ͸ ͻͻǤͳ ͳͲͲ ͻͻǤʹ ͻͻǤ͹ ͻͻǤͺ ͻͻǤ͵ ͻͻǤͻ ʹǤͻȋͳ͹ǤͷȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵͸Ȍ ȋʹ͹͸͸Ȍ ȋͺͺǤͲͶȌ
     ʹͷͺ ͻͷǤͲ ͻͺǤͺ ͻͻǤʹ ͳͲͲ ͻ͸Ǥͻ ͻͻǤʹ ͻͻǤʹ ͻͺǤͶ ͳͲͲ ͶǤͻȋͳͻǤ͹Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͺȌ ȋʹͻͺͳȌ ȋͺͺǤ͸͵Ȍ
    Š‘Žƒ‰‹‘Ǧ ͵Ͳʹ ͻ͸ǤͲ ͻͺǤ͸ ͻͻǤ͵ ͻͻǤ͹ ͻͻǤͲ ͻͻǤ͵ ͳͲͲ ͻͻǤ͵ ͳͲͲ ͳǤʹȋͳ͵ǤͷȌ
    ƒ” ‹‘ƒ ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤͶͷȌ ȋʹͻͳͳȌ ȋͺͺǤͻͷȌ
    ‘Ž‘”‡ –ƒŽ ͳͲͶͳ ͻ͸Ǥͷ ͻͺǤͺ ͻͻǤͷ ͳͲͲ ͻ͹Ǥͺ ͻͺǤ͹ ͻͻǤͺ ͻͻǤ͵ ͳͲͲ ͷǤ͵ȋʹͳǤͳȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵͸Ȍ ȋʹͺ͵ʹȌ ȋͺͺǤ͵͵Ȍ
    ƒ•–”‘‡•‘’Šƒ‰‡ƒŽ ͶͶ͵ ͻ͸Ǥʹ ͻͻǤͲ ͳͲͲ ͳͲͲ ͻͺǤʹ ͻͺǤͶ ͳͲͲ ͻͻǤ͹ ͳͲͲ ͵Ǥͳȋͳ͹Ǥ͹Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵͹Ȍ ȋʹ͹ͻͲȌ ȋͺͺǤ͵ͶȌ
    ›‡ ‘Ž‘‰‹ ƒŽ ͵ʹʹ ͻͷǤͶ ͻͺǤͲ ͻͻǤ͹ ͳͲͲ ͻ͹Ǥͷ ͻͺǤ͹ ͳͲͲ ͻͻǤ͹ ͻͻǤͳ ͵ǤͳȋͳͺǤͷȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͲȌ ȋʹ͹͹ͳȌ ȋͺͺǤͳͷȌ

    ͵ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Patient Sample
    Sample Preparation QC Sequencing QC Data, %
    Category Data Data, % Pass Pass (median value) Patient Outcome Metrics
    ‡ƒ†ƒ†‡  ͻͺ ͻͶǤͻ ͻ͸Ǥ͹ ͳͲͲ ͻͻǤͲ ͻͻǤͲ ͳͲͲ ͻͻǤͲ ͳͲͲ ͳͲͲ ʹǤͺȋͳ͹ǤͲȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹ͵Ȍ ȋʹ͵ͻͻȌ ȋͺ͹ǤͺͷȌ
    ‹˜‡” ͸͹ ͻͳǤͲ ͳͲͲ ͳͲͲ ͳͲͲ ͻ͹ǤͲ ͳͲͲ ͻͺǤͷ ͻ͹ǤͲ ͳͲͲ ͳǤʹȋͳ͸ǤͷȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤͷͲȌ ȋʹͺͺͲȌ ȋͺͺǤ͸ͺȌ
    —‰“—ƒ‘—• ͷͺͶ ͻ͹Ǥ͸ ͻͺǤʹ ͻͻǤ͸ ͳͲͲ ͻͻǤͺ ͳͲͲ ͳͲͲ ͻͻǤ͹ ͳͲͲ ʹǤʹȋͳͶǤ͹Ȍ
    ‡ŽŽƒ” ‹‘ƒ ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹ͹Ȍ ȋʹͺͳʹȌ ȋͺͺǤ͵ͳȌ
    —‰ ƒ ‡”ǡ ͳͷʹ ͻ͵ǤͶ ͻͷǤ͸ ͳͲͲ ͳͲͲ ͻͺǤ͹ ͻͺǤ͹ ͳͲͲ ͻͻǤ͵ ͻͻǤ͵ ͶǤͳȋͳͻǤͳȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͻȌ ȋʹͺ͵͹Ȍ ȋͺͺǤͲͳȌ
    ‡Žƒ‘ƒ ͳ͹Ͷ ͻͲǤͺ ͻͲǤͶ ͻͻǤͶ ͳͲͲ ͻͻǤͶ ͳͲͲ ͳͲͲ ͳͲͲ ͻͺǤͺ ͳǤ͵ȋͳͷǤ͵Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹͷȌ ȋʹͶ͵ͻȌ ȋͺ͹ǤͻͲȌ
    ‡•‘–Š‡Ž‹‘ƒ ͳʹ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͲǤ͵ȋʹǤͷȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹͲȌ ȋʹͻ͸ͺȌ ȋͺ͹Ǥ͹ʹȌ
     Ͷͳͳͳ ͻ͸Ǥͳ ͻ͹Ǥ͸ ͻͻǤͶ ͳͲͲ ͻͻǤͲ ͻͻǤͷ ͻͻǤͻ ͻͻǤͶ ͻͻǤͻ ͳǤ͹ȋͳͶǤ͵Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹͻȌ ȋʹ͸͹ͳȌ ȋͺͺǤͲͶȌ
    ‡—”‘‡†‘ ”‹‡ ͳͲͲ ͻͲ ͻ͵Ǥ͸ ͻͺǤͻ ͳͲͲ ͻͺ ͳͲͲ ͳͲͲ ͻͺ ͻͺ ʹǤͷȋʹͳǤ͹Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤͶͳȌ ȋʹ͹ͷͺȌ ȋͺ͹ǤͻͳȌ
    –Š‡” Ͷͳͻ ͻͷǤ͹ ͻ͹Ǥͻͷ ͻͻǤͷ ͳͲͲ ͻ͹Ǥͺ ͻͻǤ͵ ͻͻǤ͵ ͻͺǤͺ ͻͻǤͲ ʹǤͲȋͳ͹Ǥ͵Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͲȌ ȋʹ͹͵ͲȌ ȋͺͺǤͳͳȌ
    ƒ ”‡ƒ–‹  ͷͺͳ ͻͷǤͻ ͻ͹Ǥ͸ ͻͺǤͷ ͳͲͲ ͻͻǤͲ ͳͲͲ ͳͲͲ ͻͻǤ͵ ͳͲͲ ͲǤͻȋͳ͵ǤͻȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͷȌ ȋʹͺͶ͵Ȍ ȋͺͺǤͳʹȌ
    ”‹ƒ”› Ͷ͹ ͻ͵Ǥ͸ ͻ͵Ǥ͵ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͲǤʹȋͲǤ͵Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͷȌ ȋʹͶ͵ͳȌ ȋͺͺǤʹͺȌ
    ”‘•–ƒ–‡ ͹͹Ͳ ͻͶǤͻ ͻͺǤͲ ͻͻǤ͵ ͳͲͲ ͻ͹Ǥͷ͵ ͻͻǤͲͻ ͻͻǤͻ ͻͺǤ͸ ͻͻǤͷ ͵ǤͲȋͳͻǤ͸Ȍ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͶȌ ȋʹ͹Ͳ͸Ȍ ȋͺͺǤͳͶȌ
    ‡ƒŽ ͺͻ ͻͷǤͷ ͻ͹Ǥ͸ ͻͺǤͺ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͻͺǤͻ ͳͲͲ ͲǤͺȋ͸ǤͺȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹͺȌ ȋʹ͹͵ͻȌ ȋͺ͹Ǥ͸͵Ȍ
     ͳ͵͸ ͻͷǤ͸ ͻͺǤͷ ͻͻǤ͵ ͳͲͲ ͻͻǤʹ͸ ͳͲͲ ͳͲͲ ͻͺǤͷ ͳͲͲ ͵ǤͲȋʹͶǤͷȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵ͶȌ ȋʹ͹ͲͳȌ ȋͺͺǤ͵ͶȌ
    ‘ˆ–‹••—‡ ͻͳ ͻͺǤͻ ͻͺǤͻ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳǤʹȋͳʹǤͺȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵͸Ȍ ȋʹͺͶͶȌ ȋͺͺǤʹ͸Ȍ
    Š›”‘‹† Ͷ͹ ͻ͹Ǥͻ ͻ͹Ǥ͸ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͳͲͲ ͲǤͷȋ͵ǤʹȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤ͵͵Ȍ ȋʹͺͲͻȌ ȋͺ͹Ǥ͹͸Ȍ
    ”‘–Š‡Ž‹ƒŽ ͳͶ͹ ͻͻǤ͵ ͻͻǤ͵ ͳͲͲ ͳͲͲ ͻͺǤ͸Ͷ ͻͺǤ͸Ͷ ͳͲͲ ͳͲͲ ͳͲͲ ʹǤ͸ȋͳͷǤʹȌ
    ȋͲǤͲͳȌ ȋͲǤͲȌ ȋͳǤʹ͸Ȍ ȋʹ͸͸ͲȌ ȋͺ͹ǤͺʹȌ

    ‘ƒ••‡••–Š‡‹’ƒ –‘ˆ ƒ ‡”–›’‡‘–Š‡˜ƒ”‹ƒ–‹‘‘ˆ ‘–‹—‘—•‡–”‹ •ƒ† –•Š‡††‹‰


    Ž‡˜‡Žǡ–Š‡’‡” ‡–‘ˆ˜ƒ”‹ƒ–‹‘‡š’Žƒ‹‡†„› ƒ ‡”–›’‡™‹–Š˜ƒ”‹ƒ ‡ ‘’‘‡–ƒƒŽ›•‹•™ƒ•
    ‡•–‹ƒ–‡†Ǥƒ”‹ƒ– ‘’‘‡–ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†ˆ‘” ˆ›‹‡Ž†ǡ‡”‹ Š‡–‘Žƒ”‹–›ǡ „‹ƒ•ǡ
    ‘Ǧ•‹‰Ž‡–‘ ‘˜‡”ƒ‰‡ǡ‘–ƒ”‰‡–”ƒ–‡ǡƒ†ƒš‹— Ǥƒ ‡”–›’‡•‡š’Žƒ‹‡†‘‘”‡–Šƒ
    ʹǤͻΨ‘ˆ–Š‡˜ƒ”‹ƒ ‡ƒ ”‘••ƒŽŽ‡–”‹ •–‡•–‡†ǡ‹ Ž—†‹‰ˆƒ –‘”•Ž‹‡†–‘ƒ••ƒ›•‡•‹–‹˜‹–›•— Šƒ•
    ˆ›‹‡Ž†•ǡ†‡’–Š‘ˆ ‘˜‡”ƒ‰‡ƒˆ–‡”Ž‹„”ƒ”›’”‡’ƒ”ƒ–‹‘ƒ†•‡“—‡ ‹‰ǡƒ†–Š‡Ž‡˜‡Ž•‘ˆ –
    •Š‡††‹‰Ǥ
    –•Š‡††‹‰Ž‡˜‡Ž•ƒ”‡•Š‘™„‡Ž‘™ȋFigure 1Ȍ„› ƒ ‡”–›’‡Ǥƒš‹— •‡”˜‡†ƒ•ƒ’”‘š›
    ˆ‘” –•Š‡††‹‰ǡƒ†ƒš‹— ”ƒ‰‡•™‡”‡•‹‹Žƒ”ˆ‘”ƒŽŽ ƒ ‡”–›’‡•ǡ‡š ‡’–’”‹ƒ”›
    –—‘”•ǤŠ‡†‹ˆˆ‡”‡ ‡‹ –•Š‡††‹‰”ƒ–‡†ƒ›„‡‡š’Žƒ‹‡†„›–—‘”•„‡‹‰Ž‘ ƒ–‡†
    „‡Š‹†–Š‡„Ž‘‘†Ǧ„”ƒ‹„ƒ””‹‡”ǡ™Š‹ Š‹’ƒ‹”•–Š‡–”ƒ•ˆ‡”‘ˆ –ˆ”‘–Š‡–‘–Š‡’‡”‹’Š‡”›ǡ
    ™‹–Šƒ ‘ ‘‹–ƒ–†‡ ”‡ƒ•‡‹–›’‹ ƒŽ –Ž‡˜‡Žƒ††‡–‡ –‹‘”ƒ–‡Ǥ –†‡–‡ –‹‘‹•Š‹‰Š‹
    ƒ†ǡ‹™Š‹ Š–Š‡‘•– ‘‘‰‡‘‹ ƒŽ–‡”ƒ–‹‘•ƒ”‡”‡’”‡•‡–‡†‘–Š‡ —ƒ”†ƒ–͵͸Ͳ
    š’ƒ‡ŽǢŠ‘™‡˜‡”ǡ –†‡–‡ –‹‘”ƒ–‡•ƒ”‡Ž‘™‡”‹‡•‘–Š‡Ž‹‘ƒƒ†”‡ƒŽ ‡ŽŽ ƒ” ‹‘ƒǡƒ•
    —–ƒ–‹‘•‹–Š‡ —ƒ”†ƒ–͵͸Ͳš”‡’‘”–ƒ„Ž‡”ƒ‰‡ƒ”‡Ž‡•• ‘‘‹–Š‡•‡–—‘”–›’‡•ǡ”‡•—Ž–‹‰
    ‹Ž‘™‡” –†‡–‡ –‹‘”ƒ–‡Ǥ

    ͵ʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    
    ‘–‡–Šƒ–Ǧƒš‹•”‡’”‡•‡–•Ψƒš‹— 
    Figure 1. Maximum MAF Distribution by Cancer Type
    ƒ††‹–‹‘–‘–Š‡•‡‡–”‹ •ǡ ˆˆ”ƒ‰‡–†‹•–”‹„—–‹‘•‹ƒŽƒ”‰‡ ‘Š‘”–‘ˆ Ž‹‹ ƒŽ’ƒ–‹‡–
    •ƒ’Ž‡•™ƒ•‡šƒ‹‡†–‘†‡‘•–”ƒ–‡•‹‹Žƒ”‹–›‘ˆ’”‘ˆ‹Ž‡•ƒ ”‘•• ƒ ‡”–›’‡•Ǥ‹‹Žƒ”–‘‘–Š‡”
    ‡–”‹ •ǡ ƒ ‡”–›’‡‡š’Žƒ‹‡†Ž‡••–ŠƒͳΨ‘ˆ–Š‡˜ƒ”‹ƒ ‡‹–Š‡Ž‘ ƒ–‹‘•‘ˆ–Š‡ ˆˆ”ƒ‰‡–•‹œ‡
    ’”‘ˆ‹Ž‡’‡ƒǤ

    ͸ǤͳʹǤ ‘ ‘”†ƒ ‡Ǧ —ƒ”†ƒ–͵͸Ͳš‘’ƒ”‹•‘–‘ —ƒ”†ƒ–͵͸Ͳ


    •–—†›™ƒ•’‡”ˆ‘”‡†–‘‡•–ƒ„Ž‹•Š–Š‡ ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ† —ƒ”†ƒ–͵͸Ͳ
    ǤŠ‡’—”’‘•‡‘ˆ–Š‹••–—†›™ƒ•–‘ ‘’ƒ”‡–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ‰ƒ‹•–ƒ —ƒ”†ƒ–͵͸Ͳ
    ‘ˆ‹‰—”ƒ–‹‘—•‡†–‘‰‡‡”ƒ–‡Š‹•–‘”‹ ƒŽ†ƒ–ƒƒ†‹•‹–‡†‡†–‘•—’’‘”––Š‡—•‡‘ˆ–Š‘•‡”‡•—Ž–•ƒ•
    ”‡’”‡•‡–ƒ–‹˜‡‘ˆ —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•Ǥ
    Š‡†‡•‹‰ƒ† ‘’‘•‹–‹‘‘ˆ–Š‡•‡–™‘†‡˜‹ ‡•‹••‹‹Žƒ”ǡƒ•–Š‡›•Šƒ”‡–Š‡•ƒ‡’”‹ ‹’Ž‡•‘ˆ
    ‘’‡”ƒ–‹‘ǤŠ‡’”‹ƒ”›†‹ˆˆ‡”‡ ‡•‹†‡•‹‰ƒ”‡–Š‡’ƒ‡Ž™‹–Š™Š‹ Š–Š‡†‡˜‹ ‡‹•‘’‡”ƒ–‡†ǤŠ‡
    —ƒ”†ƒ–͵͸Ͳ˜‡”•‹‘—•‡†ˆ‘”†ƒ–ƒ‰‡‡”ƒ–‹‘‹•—’’‘”–‘ˆ ‘ ‘”†ƒ ‡–‘–Š‡ —ƒ”†ƒ–͵͸Ͳ
    š–‡•–‹–Š‹••–—†›™ƒ•‘’‡”ƒ–‡†™‹–Š˜‡”•‹‘ʹǤͳͲ‘ˆ–Š‡’ƒ‡Žǡ™Š‹ Š ‘˜‡”•͹͵‰‡‡•ǤŠ‡
    —ƒ”†ƒ–š‹•‘’‡”ƒ–‡†™‹–Š˜‡”•‹‘ʹǤͳͳ‘ˆ–Š‡’ƒ‡Žǡ™Š‹ Š ‘˜‡”•͹Ͷ‰‡‡•ǤŠ‹Ž‡–Š‡
    —ƒ”†ƒ–͵͸Ͳš ƒ†‡–‡ –ƒŽ–‡”ƒ–‹‘•‹͹Ͷ‰‡‡•ǡ‹–‘Ž›”‡’‘”–••‡Ž‡ –•ƒ†‹†‡Ž•‹ͷͷ
    ‰‡‡•ǡ•‹–™‘ȋʹȌ‰‡‡•ǡƒ†ˆ—•‹‘•‹ˆ‘—”ȋͶȌ‰‡‡•ǤŠ‡ ‘ ‘”†ƒ ‡ƒƒŽ›•‹•„‡–™‡‡–Š‡
    —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡ —ƒ”†ƒ–͵͸Ͳ‹•Ž‹‹–‡†–‘ͷͷ‰‡‡”‡•–”‹ –‡†”‡’‘”–ƒ„Ž‡”ƒ‰‡ǤŠ‹•
    ‘ ‘”†ƒ ‡ƒƒŽ›•‹•—–‹Ž‹œ‡†–Š‡„‹‘‹ˆ‘”ƒ–‹ •’‹’‡Ž‹‡•‘ˆ–™ƒ”‡ ‘””‡•’‘†‹‰–‘‡ƒ Šƒ••ƒ›
    ˜‡”•‹‘Ǥ
    Š‹••–—†›‡˜ƒŽ—ƒ–‡†ƒ•‡–‘ˆʹͷͺ•ƒ’Ž‡•™‹–ŠƒŽ–‡”ƒ–‹‘•‹‰‡‡•‹–‡””‘‰ƒ–‡†„›„‘–Šƒ••ƒ›•ǡƒˆ–‡”
    ”‡‘˜‹‰ʹ•ƒ’Ž‡•–Šƒ–ˆƒ‹Ž‡†‡–”‹ •ǤŠ‡•–—†›‹ Ž—†‡† ˆ†‡”‹˜‡†ˆ”‘ʹʹ ƒ ‡”–›’‡•ǡ
    ‘’”‹•‹‰–™‘†‹•–‹ –•ƒ’Ž‡•‡–•ǤŠ‡ˆ‹”•–•‡–™ƒ••‡Ž‡ –‡† ‘•‡ —–‹˜‡Ž›ˆ”‘ƒ‘‰•ƒ’Ž‡•
    ˆ”‘’ƒ–‹‡–•™‹–Š’‘•‹–‹˜‡ˆ‘” —ƒ”†ƒ–͵͸Ͳš˜ƒ”‹ƒ–•ƒ ‘”†‹‰–‘ —ƒ”†ƒ–͵͸Ͳ
    ˜ƒ”‹ƒ– ƒŽŽ‹‰”—Ž‡•ǡ–ƒ”‰‡–‹‰–‘‘„–ƒ‹ƒ‹‹—‘ˆͷͲ˜ƒŽ‹†•ƒ’Ž‡”‡•—Ž–•ˆ‘”EGFRͺͷͺǡͷͲˆ‘”
    EGFR‡š‘ͳͻ†‡Ž‡–‹‘•ǡƒ†͹ͷˆ‘”EGFR͹ͻͲ—–ƒ–‹‘ǤŠ‡•‡ ‘†•‡–™ƒ••‡Ž‡ –‡† ‘•‡ —–‹˜‡Ž›
    ͵͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ™‹–Š‘—– ‘•‹†‡”ƒ–‹‘ˆ‘”–—‘”–›’‡‘”’”‡˜‹‘—•–‡•–‹‰”‡•—Ž–•Ǥ‡”–Š‡•–—†›’”‘–‘ ‘Ž•ƒ’Ž‡•™‹–Š
    •’‡ ‹ˆ‹ •‡–‘ˆ”ƒ”‡˜ƒ”‹ƒ–•™‡”‡‡š Ž—†‡†ˆ”‘–Š‡•–—†›ǤDzƒ”‡dzŠ‡”‡™ƒ•†‡ˆ‹‡†„› —ƒ”†ƒ–
    ‡ƒŽ–Šƒ•δͳΨ’”‡˜ƒŽ‡ ‡‘”–‘”ƒ”‡ˆ—•‹‘‡˜‡–•ȋ e.g.NTRK1ǡROS1Ȍǡƒ†MET‡š‘ͳͶ•‹’’‹‰
    ˜ƒ”‹ƒ–•Ǥ ƒ††‹–‹‘ǡ™Š‡‘™–‘ —ƒ”†ƒ– ‡ƒŽ–Š„ƒ•‡†‘’”‹‘”–‡•–‹‰‘”’ƒ–Š‘Ž‘‰›
    ”‡’‘”–•ǡ•ƒ’Ž‡•ˆ”‘’ƒ–‹‡–•ˆ‘”™Š‘–—‘”•ƒ”‡ ‘•‹†‡”‡†–—‘”—–ƒ–‹‘ƒŽ„—”†‡ȋȌ
    Š‹‰Šǡ‹ ”‘•ƒ–‡ŽŽ‹–‡‹•–ƒ„‹Ž‹–›Š‹‰Šȋ Ǧ Ȍǡ‘”Ǧͳ’‘•‹–‹˜‡™‡”‡ƒŽ•‘‡š Ž—†‡†Ǥ –‘–ƒŽǡ‘Ž›ͳ
    •ƒ’Ž‡™ƒ•‡š Ž—†‡†ǡƒ•‹– ‘–ƒ‹‡†ƒALKˆ—•‹‘Ǥ
    Š‡ ƒ ‡”–›’‡•”‡’”‡•‡–‡†‹–Š‹• ‘ ‘”†ƒ ‡•–—†›™‡”‡‘„–ƒ‹‡†ˆ”‘’ƒ–‹‡–•™‹–Š
    ͳͻͷ Ȍǡ‰ƒ•–”‘‹–‡•–‹ƒŽ–—‘”•ȋʹʹȌǡ‰‡‹–‘—”‹ƒ”›–—‘”•ȋʹͲȌǡ„”‡ƒ•– ƒ ‡”ȋͳͶȌǡ‰›‡ ‘Ž‘‰‹ ƒŽ
    –—‘”•ȋͶȌǡƒ†‘–Š‡”•‘Ž‹†–—‘”•ȋͶȌǤ
    ƒ†„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ† —ƒ”†ƒ–͵͸Ͳǡ—•‹‰–Š‡ —ƒ”†ƒ–͵͸Ͳƒ••ƒ›ƒ•
    –Š‡”‡ˆ‡”‡ ‡‡–Š‘†ǡ™ƒ• ƒŽ —Žƒ–‡†ˆ‘”ƒŽŽƒŽ–‡”ƒ–‹‘•Ǥ–‘–ƒŽ‘ˆʹ͹ͻ•ǡͳͳ͹‹†‡Ž•ǡƒ†ʹ͵•
    ‡––Š‡ƒŽ–‡”ƒ–‹‘‹ Ž—•‹‘ ”‹–‡”‹ƒǤ•—ƒ”›‘ˆƒ†‹•’”‘˜‹†‡†‹Table 28Ǥˆ‘”–Š‡
    š˜ƒ”‹ƒ–•ƒ•™‡ŽŽƒ•’ƒ‡ŽǦ™‹†‡•ǡ‹†‡Ž•ǡƒ† Ž‹‹ ƒŽŽ›•‹‰‹ˆ‹ ƒ–˜ƒ”‹ƒ–••Š‘™‡†™ƒ•ƒ„‘˜‡
    ͻͶΨ‹ƒŽŽ ƒ•‡•ǡ™Š‡”‡ƒ•’‘•‹–‹˜‡ƒ‰”‡‡‡–Ž‡˜‡Ž•™‡”‡Ž‘™ˆ‘”ERBB2ƒ†METƒ’Ž‹ˆ‹ ƒ–‹‘•Ǥ
    ‰”‡‡‡–Ž‡˜‡Ž•™‡”‡Ž‘™ˆ‘”ERBB2ƒ†METƒ’Ž‹ˆ‹ ƒ–‹‘•ƒ•ƒ’Ž‹ˆ‹ ƒ–‹‘Ž‡˜‡Ž•ˆ‘”͹ͲΨ‘ˆ
    •ƒ’Ž‡•–‡•–‡†™‡”‡‡ƒ”–Š‡†‡ ‹•‹‘„‘—†ƒ”›ȋδͳǤͷš‘ȌǤ ‹‰Š™ƒ•‘„•‡”˜‡†‹ƒŽŽ Žƒ••‡•Ǥ
    ‘ ‘”†ƒ ‡„‡–™‡‡–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡ —ƒ”†ƒ–͵͸Ͳˆ‘”–Š‡ˆ‘—”ˆ—•‹‘•”‡’‘”–‡†
    „›–Š‡ —ƒ”†ƒ–͵͸ͲšȋROS1ǡALKǡNTRK1ǡƒ†RETȌ‹•—‘™ƒ•‹–™ƒ•‘–‡˜ƒŽ—ƒ–‡†Ǥ

    Table 28. Summary of Concordance between Guardant360 CDx and Guardant360 LDT
    CDx+ CDx− CDx+ CDx− PPA NPA
    Alteration Type LDT+ LDT+ LDT− LDT− (95% CI) (95% CI)
    EGFR͹ͻͲ ͺ͹ Ͷ ͷ ͻͻ ͻͷǤ͸Ψ ͻͷǤʹΨ
    ȋͺͻǤͳΨǡͻͺǤͺΨȌ ȋͺͻǤͳΨǡͻͺǤͶΨȌ
    EGFRͺͷͺ ͷʹ ͳ Ͷ ͳ͵ͺ ͻͺǤͳΨ ͻ͹ǤʹΨ
    ȋͺͻǤͻΨǡͳͲͲΨȌ ȋͻʹǤͻΨǡͻͻǤʹΨȌ
    EGFR‡š‘ͳͻ ͺͻ ͵ ʹ ͳͲͳ ͻ͸Ǥ͹Ψ ͻͺǤͳΨ
    †‡Ž‡–‹‘• ȋͻͲǤͺΨǡͻͻǤ͵ΨȌ ȋͻ͵ǤʹΨǡͻͻǤͺΨȌ
    Ž‹‹ ƒŽŽ› ʹͺʹ ͳ͸ ͳͶ ͻ͹Ͷͻͺ ͻͶǤ͸Ψ ͻͻǤͻͺΨ
    ‹‰‹ˆ‹ ƒ– ȋͻͳǤͶΨǡͻ͸ǤͻΨȌ ȋͻͻǤͻ͹ΨǡͻͻǤͻͻΨȌ
    ƒ‡ŽǦ‹†‡ ʹͶʹ ͳͷ ʹͳ ͳͲͷ͸Ͷ͹ ͻͶǤʹΨ ͻͻǤͻͺΨ
    ȋͻͲǤ͸Ψǡͻ͸Ǥ͹ΨȌ ȋͻͻǤͻ͹ΨǡͻͻǤͻͻΨȌ
    ƒ‡ŽǦ‹†‡ †‡Ž ͳͲʹ ͷ ͹ ͷͲ͹͸ͺ ͻͷǤ͵Ψ ͻͻǤͻͻΨ
    ȋͺͻǤͶΨǡͻͺǤͷΨȌ ȋͻͻǤͻ͹ΨǡͻͻǤͻͻΨȌ
    MET ͳʹ Ͷ Ͳ ʹͶʹ ͹ͷǤͲΨ ͳͲͲΨ
    ȋͶ͹Ǥ͸ΨǡͻʹǤ͹ΨȌ ȋͻͺǤͶͻΨǡͳͲͲΨȌ
    ERBB2 ͷ ʹ Ͳ ʹͷͳ ͹ͳǤͶΨ ͳͲͲΨ
    ȋʹͻǤͲͶΨǡͻ͸Ǥ͵͵ΨȌ ȋͻͺǤͷͶΨǡͳͲͲΨȌ

    Š‡ ‘ ‘”†ƒ ‡•–—†›ƒŽ•‘ ‘’ƒ”‡†–Š‡ —ƒ”†ƒ–͵͸Ͳš–‘–Š‡ —ƒ”†ƒ–͵͸Ͳ™Š‹ Š™ƒ•ƒŽ•‘


    —•‡†‹–Š‡ ƒ†͵ Ž‹‹ ƒŽ•–—†‹‡•–‘•—’’‘”––Š‡EGFRš‹†‹ ƒ–‹‘Ǥ
    Š‡ ‘ ‘”†ƒ ‡ƒƒŽ›•‹•’”‡•‡–‡†„‡Ž‘™‹Table 29‹•ˆ‘”–Š‡EGFRš˜ƒ”‹ƒ–•‹’ƒ–‹‡–
    •ƒ’Ž‡•‘Ž›ȋͳͻͷ‘—–‘ˆʹͷͺȌǤ‘ ‘”†ƒ ‡ƒƒŽ›•‡•„‡–™‡‡–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ†
    —ƒ”†ƒ–͵͸Ͳ—–‹Ž‹œ‡†–Š‡„‹‘‹ˆ‘”ƒ–‹ •’‹’‡Ž‹‡•‘ˆ–™ƒ”‡ ‘””‡•’‘†‹‰–‘–Š‡ —ƒ”†ƒ–͵͸Ͳ
    šƒ’’Ž‹‡†–‘–Š‡ —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•Ǥ

    ͵Ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 29. Summary of Concordance between Guardant360 CDx and Guardant360 LDT
    CDx+ CDx− CDx+ CDx− PPA NPA
    Alteration Type LDT+ LDT+ LDT− LDT− (95% CI) (95% CI)
    EGFR͹ͻͲ ͺ͹ Ͷ ͷ ͻͻ ͻͷǤ͸Ψ ͻͷǤʹΨ
    ȋͺͻǤͳΨǡͻͺǤͺΨȌ ȋͺͻǤͳΨǡͻͺǤͶΨȌ
    EGFRͺͷͺ ͷʹ ͳ Ͷ ͳ͵ͺ ͻͺǤͳΨ ͻ͹ǤʹΨ
    ȋͺͻǤͻΨǡͳͲͲΨȌ ȋͻʹǤͻΨǡͻͻǤʹΨȌ
    EGFR‡š‘ͳͻ ͺͻ ͵ ʹ ͳͲͳ ͻ͸Ǥ͹Ψ ͻͺǤͳΨ
    †‡Ž‡–‹‘• ȋͻͲǤͺΨǡͻͻǤ͵ΨȌ ȋͻ͵ǤʹΨǡͻͻǤͺΨȌ

    ƒ††‹–‹‘–‘–Š‡ ‘ ‘”†ƒ ‡•–—†›†‡• ”‹„‡†ƒ„‘˜‡ǡ–Š‡ƒƒŽ›–‹ ƒŽ’‡”ˆ‘”ƒ ‡™‹–Š”‡‰ƒ”†•–‘‘


    ƒ†’”‡ ‹•‹‘™ƒ•ˆ‘—†–‘„‡ ‘’ƒ”ƒ„Ž‡„‡–™‡‡–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡ —ƒ”†ƒ–͵͸Ͳ
    ™‹–Š”‡‰ƒ”†•–‘–Š‡EGFRš˜ƒ”‹ƒ–•Ǥ

    ͸Ǥͳ͵Ǥ ††‹–‹‘ƒŽ–—†‹‡•

    a. Blood Collection Tube Concordance


    Š‡’—”’‘•‡‘ˆ–Š‹••–—†›™ƒ•–‘‡•–ƒ„Ž‹•Š ‘ ‘”†ƒ ‡„‡–™‡‡–Š‡–”‡ ‡ŽŽǦ ”‡‡•ƒ†
    •—•‡†‹–Š‡ Ž‹‹ ƒŽ–”‹ƒŽ•ȋŠ‡”‡ƒˆ–‡””‡ˆ‡””‡†–‘ƒ•ǦȌ–‘‡ƒ„Ž‡—•‡‘ˆ —ƒ”†ƒ–͵͸Ͳš
    †ƒ–ƒ‰‡‡”ƒ–‡†ˆ”‘–Š‡ ƒ†͵ Ž‹‹ ƒŽ–”‹ƒŽ•ȋ”‡ˆ‡”–‘Section 7. Summary of Primary
    Clinical Studies Ǥ
    Ž‘‘†ˆ”‘–ƒ‰‡ ‘” ’ƒ–‹‡–•ǡ’”‡• ”‡‡‡†‡š–‡”ƒŽŽ›ˆ‘”š’‘•‹–‹˜‡ƒ†‡‰ƒ–‹˜‡
    ƒ”‡”•ȋEGFRͺͷͺǡEGFR͹ͻͲǡEGFR‡š‘ͳͻ†‡Ž‡–‹‘•Ȍǡ™‡”‡ ‘ŽŽ‡ –‡†„›—–‹Ž‹œ‹‰–™‘Ǧ
    •ƒ†–™‘–”‡ ‡ŽŽǦ ”‡‡•ǤŠ‡•‡ ‘†Ǧ™ƒ•‘–’”‘ ‡••‡†ˆ‘”–Š‹••–—†›Ǥ
    –‘–ƒŽ‘ˆͷͻ’ƒ–‹‡–•™‡”‡‡”‘ŽŽ‡†ǡ•‘‡™‹–Šƒ†‘–Š‡”•™‹–Š‘—–š˜ƒ”‹ƒ–•ǡƒ†™Š‘Ž‡„Ž‘‘†
    •ƒ’Ž‡•™‡”‡–‡•–‡†ˆ”‘–Š”‡‡–—„‡•ǡ–™‘–”‡ ‡ŽŽǦ ”‡‡•ƒ†‘‡ǦǤ
    Š‡’‡”ˆ‘”ƒ ‡‘ˆǦ•”‡Žƒ–‹˜‡–‘–”‡ ‡ŽŽǦ ”‡‡•™ƒ•‡˜ƒŽ—ƒ–‡†–Š”‘—‰Šƒ ƒŽŽ
    ƒ‰”‡‡‡–ƒƒŽ›•‹•™Š‹ Š–‡•–•–Š‡†‹ˆˆ‡”‡ ‡‘ˆ–Š‡‘ˆ–”‡ Žƒ•ƒŽ‹“—‘–ʹȋʹȌ–‘–”‡ 
    Žƒ•ƒŽ‹“—‘–ͳȋͳȌƒ†–Š‡‘ˆǦŽƒ•ƒŽ‹“—‘–ͳȋͳȌ–‘ͳȋ†‹ˆˆ‡”‡ ‡†‡‘–‡†ƒ•
    ȟͳȌǤȟʹ‹• ƒŽ —Žƒ–‡†•‹‹Žƒ”Ž›‡š ‡’––Šƒ–ʹ‹• ‘•‹†‡”‡†–Š‡”‡ˆ‡”‡ ‡‹•–‡ƒ†‘ˆͳǤ ‘”
    ‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ǡȟͳƒ†ȟʹƒ”‡ƒŽ•‘ ƒŽ —Žƒ–‡†‹ƒ•‹‹Žƒ”ˆƒ•Š‹‘Ǥ
    ˆ–Š‡‘‡ǦŠ—†”‡†ƒ†•‡˜‡–›Ǧ•‡˜‡ȋͳ͹͹ȌƒŽ‹“—‘–•ȋͷͻ•ƒ’Ž‡•ƒ ”‘••͵–—„‡†‡•‹‰ƒ–‹‘•Ȍǡͳ͹͸
    ȋͻͻǤͶΨȌ’ƒ••‡†‹Ǧ’”‘ ‡••ƒ†’‘•–Ǧ•‡“—‡ ‹‰‡–”‹ •Ǥˆ–Š‡ͳ͹͸’ƒ••‹‰’‘•–Ǧ•‡“—‡ ‹‰
    ‡–”‹ •ǡʹˆƒ‹Ž‡†•ƒ’Ž‡ǡŽ‡ƒ˜‹‰ͳ͹Ͷ‘ˆͳ͹͹ȋͻͺǤ͵ΨȌ•ƒ’Ž‡•’ƒ••‹‰‡–”‹ •ǤŠ”‡‡‘ˆ–Š‡ͷͻ
    ’ƒ–‹‡–•™‹–Šͳǡʹǡƒ†ͳ”—•™‡”‡‡š Ž—†‡†ˆ”‘ ƒŽŽ ‘ ‘”†ƒ ‡ƒƒŽ›•‡•„‡ ƒ—•‡‘ˆˆƒ‹Ž—”‡•
    ‘ˆƒ–Ž‡ƒ•–‘‡‘ˆ͵”‡’Ž‹ ƒ–‡•Ǥ
    –‘–ƒŽͷ͸’ƒ–‹‡–•‡–•–—†› ”‹–‡”‹ƒˆ‘”‹ Ž—•‹‘ǡ‹ Ž—†‹‰ʹ͸†‹•–‹ –š˜ƒ”‹ƒ–•‘„•‡”˜‡†‹ƒ–
    Ž‡ƒ•–‘‡–—„‡ǤŠ‡ƒ†˜ƒŽ—‡•ƒ ”‘••–Š‡‡–‹”‡•‡–‘ˆš˜ƒ”‹ƒ–•ȋƒ‰‰”‡‰ƒ–‡†Ȍƒ†ˆ‘”
    ‡ƒ Šš˜ƒ”‹ƒ–™‡”‡ ƒŽ —Žƒ–‡†ǤǦ•ƒ†–”‡ ‡ŽŽǦ ”‡‡•†‡‘•–”ƒ–‡†‡š’‡ –‡†
    Ž‡˜‡Ž•‘ˆ’‘•‹–‹˜‡ƒ‰”‡‡‡–ǡͻʹΨȂͻͷǤͷΨˆ‘”š˜ƒ”‹ƒ–•Ǥ‹• ‘”†ƒ–†‡–‡ –‹‘™ƒ•‘„•‡”˜‡†
    „‡Ž‘™‘ǡ™‹–Šƒ‰”‡‡‡–ƒ„‘˜‡‘„‡‹‰ͳͲͲΨǤǦ•ƒ†–”‡ –—„‡•†‡‘•–”ƒ–‡†
    ‡š’‡ –‡†Ž‡˜‡Ž•‘ˆ‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ǡͻ͹Ǥ͵ΨȂͳͲͲΨˆ‘”š˜ƒ”‹ƒ–•ǤŠ‡†‡Ž–ƒƒ††‡Ž–ƒ
    ˜ƒŽ—‡•™‡”‡™‹–Š‹ƒ ‡’–ƒ„Ž‡Ž‹‹–•Ǥ

    ͵ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    7. Summary of Primary Clinical Studies
    —ƒ”†ƒ–͵͸Ͳš ‘’”‹•‡•–Š”‡‡ ‘’ƒ‹‘†‹ƒ‰‘•–‹ • Žƒ‹•ƒ•‘–‡†‹Table 1ǣ
    ͳǤ ‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™‹–Š™Š‘•‡–—‘”•Šƒ˜‡EGFR‡š‘ͳͻ†‡Ž‡–‹‘•ǡͺͷͺ
    —–ƒ–‹‘•ǡƒ†Ȁ‘”͹ͻͲ—–ƒ–‹‘•ˆ‘”‘•‹‡”–‹‹„ȋ   ̺ –Š‡”ƒ’›
    ʹǤ ‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™‹–Š™Š‘•‡–—‘”•Šƒ˜‡EGFR‡š‘ʹͲ‹•‡”–‹‘•ˆ‘”
    ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™ȋ̺Ȍ–Š‡”ƒ’›
    ͵Ǥ ‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™‹–Š™Š‘•‡–—‘”•Šƒ˜‡KRAS ͳʹƒŽ–‡”ƒ–‹‘•ˆ‘”
    •‘–‘”ƒ•‹„ȋ̻Ȍ–Š‡”ƒ’›
    ͶǤ ‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™‹–Š™Š‘•‡–—‘”•Šƒ˜‡ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•
    ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍˆ‘”ˆƒǦ–”ƒ•–—œ—ƒ„†‡”—š–‡ ƒǦš‹ȋ  ̺Ȍ–Š‡”ƒ’›
    ͷǤ ‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™‹–Š„”‡ƒ•– ƒ ‡”™Š‘•‡–—‘”•Šƒ˜‡ESR1‹••‡•‡—–ƒ–‹‘•
    „‡–™‡‡ ‘†‘•͵ͳͲǦͷͶ͹ˆ‘”‡Žƒ ‡•–”ƒ–ȋ̻Ȍ–Š‡”ƒ’›
    •—’’‘”–‘ˆ–Š‡‘•‹‡”–‹‹„š Žƒ‹ǡ —ƒ”†ƒ– ‡ƒŽ–Š’‡”ˆ‘”‡†–™‘ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†‹‡•Ǥ 
    –Š‡ˆ‹”•–ǡ’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘’ƒ–‹‡–•”ƒ†‘‹œ‡†‹–Š‡
    •–”ƒ‡‡ ƒ  Ž‹‹ ƒŽ•–—†›ȋͲʹʹͻ͸ͳʹͷȌ™‡”‡—•‡†–‘•—’’‘”––Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••
    ‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’”‡˜‹‘—•Ž›—–”‡ƒ–‡†‡–ƒ•–ƒ–‹ ’ƒ–‹‡–•™‹–Š
    EGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•ˆ‘”‘•‹‡”–‹‹„–Š‡”ƒ’›ǤŽƒ•ƒˆ”‘ ’ƒ–‹‡–•
    ‡‰ƒ–‹˜‡ˆ‘”EGFR—–ƒ–‹‘•„›–‹••—‡–‡•–‹‰™ƒ•‘–ƒ˜ƒ‹Žƒ„Ž‡–‘”‡’”‡•‡––Š‡ —ƒ”†ƒ–͵͸ͲǦ
    ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’‘”–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲǦ’‘•‹–‹˜‡‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ••— Šǡ
    •—’’Ž‡‡–ƒŽƒ– Š‡†–‹••—‡ƒ†’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘–Š‡‘‹˜ƒ•‹˜‡˜•Ǥ ˜ƒ•‹˜‡—‰˜ƒŽ—ƒ–‹‘
    Ž‹‹ ƒŽ•–—†›ȋ–Š‡ •–—†›ǡͲ͵͸ͳͷͶͶ͵Ȍ™‡”‡—•‡†–‘‡•–‹ƒ–‡–Š‡’”‡˜ƒŽ‡ ‡‘ˆ’ƒ–‹‡–•
    ’‘•‹–‹˜‡ˆ‘”EGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸Ͳ„—–‡‰ƒ–‹˜‡„›–‹••—‡
    –‡•–‹‰–‘‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ–Š‹•’‘’—Žƒ–‹‘‘ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›Ǥ –Š‡•‡ ‘†•–—†›ǡ
    ’”‡–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘–Š‡•–”ƒ‡‡ ƒ͵ Ž‹‹ ƒŽ•–—†›
    ȋͲʹͳͷͳͻͺͳȌ™‡”‡—•‡†–‘ƒ••‡••–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš–‘ƒ‹†‹
    ‹†‡–‹ˆ›‹‰’ƒ–‹‡–•™Š‘•‡†‹•‡ƒ•‡Šƒ•’”‘‰”‡••‡†‘‘”ƒˆ–‡”EGFR–›”‘•‹‡‹ƒ•‡‹Š‹„‹–‘”
     Ȍ –Š‡”ƒ’›ƒ†™Š‘ƒ›„‡‡Ž‹‰‹„Ž‡ˆ‘”‘•‹‡”–‹‹„–Š‡”ƒ’›„ƒ•‡†‘ƒEGFR͹ͻͲ—–ƒ–‹‘Ǧ
    †‡–‡ –‡†”‡•—Ž–Ǥ
    •—’’‘”–‘ˆ–Š‡ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™š Žƒ‹ǡ —ƒ”†ƒ– ‡ƒŽ–Š’‡”ˆ‘”‡†ƒ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›
    —•‹‰„ƒ‡†’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘–Š‡   Ž‹‹ ƒŽ•–—†›ȋͲʹ͸Ͳͻ͹͹͸ȌǤŠ‡’”‹ƒ”›
    ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ ‘’”‹•‡••—„Œ‡ –•ˆ”‘–Š‡   Ž‹‹ ƒŽ•–—†›
    ™‹–Š ‡š‘ʹͲ‹•‡”–‹‘•ƒ•†‡–‡”‹‡†„›Ž‘ ƒŽ–‡•–”‡•—Ž–•ǡ™Š‘•‡†‹•‡ƒ•‡’”‘‰”‡••‡†‘‘”
    ƒˆ–‡”’Žƒ–‹—Ǧ„ƒ•‡† Š‡‘–Š‡”ƒ’›ǡƒ†™Š‘™‡”‡–”‡ƒ–‡†™‹–Š–Š‡”‡ ‘‡†‡†’Šƒ•‡ʹ†‘•‡
    ȋʹȌ‘ˆƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™Ǥ”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘–Š‡•‡•—„Œ‡ –•™‡”‡–‡•–‡†™‹–Š
    —ƒ”†ƒ–͵͸ͲšǤ•–Š‡ƒŒ‘”‹–›‘ˆ•—„Œ‡ –•‹ Ž—†‡†‹–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™
    ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘’‘•‹–‹˜‡Ž‘ ƒŽ–‹••—‡–‡•–‹‰ˆ‘” ‡š‘ʹͲ
    ‹•‡”–‹‘•ǡ•‡•‹–‹˜‹–›ƒƒŽ›•‹•–‘ƒ••‡••–Š‡’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆŽ‘ ƒŽ–‡•–Ǧ‡‰ƒ–‹˜‡ǡ —ƒ”†ƒ–͵͸Ͳš
    ’Žƒ•ƒǦ’‘•‹–‹˜‡’ƒ–‹‡–•ȋ —ƒ”†ƒ–͵͸ͲšΪŽ‘ ƒŽ–‡•–ȂȌ™ƒ•’‡”ˆ‘”‡†—•‹‰•—’’Ž‡‡–ƒŽ•ƒ’Ž‡•
    ˆ”‘–Š‡   Ž‹‹ ƒŽ•–—†›• ”‡‡ˆƒ‹Ž’‘’—Žƒ–‹‘ƒ†ƒ††‹–‹‘ƒŽ•ƒ’Ž‡•ˆ”‘–Š‡ 
    Ž‹‹ ƒŽ–—†›Ǥ
    •—’’‘”–‘ˆ–Š‡•‘–‘”ƒ•‹„š Žƒ‹ǡ —ƒ”†ƒ– ‡ƒŽ–Š’‡”ˆ‘”‡†ƒ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›—•‹‰
    „ƒ‡†•ƒ’Ž‡•ˆ”‘–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›ȋͲ͵͸ͲͲͺͺ͵ȌǤŠ‡•—„Œ‡ –•‹–Š‡‰‡
    ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘–Š‡’”‡•‡ ‡‘ˆKRAS ͳʹ‹–‹••—‡•’‡ ‹‡•
    ‘ˆ‹”‡†„›‹ƒ‰‡therascreenKRAS –‡•–Ǥ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›—•‹‰’”‡Ǧ–”‡ƒ–‡–
    ’Žƒ•ƒ•ƒ’Ž‡•ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘’ƒ–‹‡–•‡”‘ŽŽ‡†‹–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ
    •–—†›™ƒ• ‘†— –‡†–‘†‡‘•–”ƒ–‡–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘ƒ‹†‹–Š‡
    ͵͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‹†‡–‹ˆ‹ ƒ–‹‘‘ˆ’ƒ–‹‡–•™Š‘ƒ›„‡‡Ž‹‰‹„Ž‡ˆ‘”–”‡ƒ–‡–™‹–Š̻ȋ•‘–‘”ƒ•‹„Ȍ
    –Š‡”ƒ’›„ƒ•‡†‘–Š‡†‡–‡ –‹‘‘ˆ ͳʹ—–ƒ–‹‘•Ǥ••—„Œ‡ –•‹–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ
    •–—†›™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘’‘•‹–‹˜‡–‹••—‡–‡•–‹‰ˆ‘”KRAS ͳʹǡ•‡•‹–‹˜‹–›ƒƒŽ›•‹•–‘ƒ••‡••–Š‡
    ’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆ–‹••—‡Ǧ‡‰ƒ–‹˜‡ǡ —ƒ”†ƒ–͵͸Ͳš’Žƒ•ƒǦ’‘•‹–‹˜‡•—„Œ‡ –•ȋ —ƒ”†ƒ–͵͸Ͳš Ϊ
    –‹••—‡ǦȌ™ƒ•’‡”ˆ‘”‡†—•‹‰•ƒ’Ž‡•’”‘ —”‡†ˆ”‘‘–Š‡”‰‡Ǧ•’‘•‘”‡† Ž‹‹ ƒŽ•–—†‹‡•‘”
    ˜‡†‘”•Ǥ
    •—’’‘”–‘ˆ–Š‡ˆƒǦ–”ƒ•–—œ—ƒ„†‡”—š–‡ ƒǦš‹ȋ  ̺Ȍš Žƒ‹ǡ —ƒ”†ƒ– ‡ƒŽ–Š
    ’‡”ˆ‘”‡†ƒ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›—•‹‰„ƒ‡†•ƒ’Ž‡•ˆ”‘–Š‡ƒ‹‹ Š‹ƒ›‘ͺʹͲͳǦǦʹͲͶ
    Ž‹‹ ƒŽ•–—†›ȋͲ͵ͷͲͷ͹ͳͲȌǤŠ‡•—„Œ‡ –•‹–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›™‡”‡‡”‘ŽŽ‡†„ƒ•‡†
    ‘–Š‡’”‡•‡ ‡‘ˆERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ‹–‹••—‡•’‡ ‹‡•Ǥ
    Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›—•‹‰’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘’ƒ–‹‡–•
    ‡”‘ŽŽ‡†‹–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›™ƒ• ‘†— –‡†–‘†‡‘•–”ƒ–‡–Š‡•ƒˆ‡–›ƒ†
    ‡ˆˆ‡ –‹˜‡‡••‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘ƒ‹†‹–Š‡‹†‡–‹ˆ‹ ƒ–‹‘‘ˆ’ƒ–‹‡–•™Š‘ƒ›„‡‡Ž‹‰‹„Ž‡
    ˆ‘”–”‡ƒ–‡–™‹–Š ̺–Š‡”ƒ’›„ƒ•‡†‘–Š‡†‡–‡ –‹‘‘ˆERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•
    ƒ†‡š‘ʹͲ‹•‡”–‹‘•ȌǤ••—„Œ‡ –•‹–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘
    ’‘•‹–‹˜‡–‹••—‡–‡•–‹‰ˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍǡ•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•–‘ƒ••‡••–Š‡’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆ–‹••—‡Ǧ‡‰ƒ–‹˜‡ǡ —ƒ”†ƒ–͵͸Ͳš’Žƒ•ƒǦ’‘•‹–‹˜‡•—„Œ‡ –•
    ȋ —ƒ”†ƒ–͵͸ͲšΪ–‹••—‡ǦȌ™ƒ•’‡”ˆ‘”‡†—•‹‰•ƒ’Ž‡•’”‘ —”‡†ˆ”‘ ‘‡” ‹ƒŽ˜‡†‘”•Ǥ
    •—’’‘”–‘ˆ–Š‡‡Žƒ ‡•–”ƒ–š Žƒ‹ǡ —ƒ”†ƒ– ‡ƒŽ–Š’”‘•’‡ –‹˜‡Ž›–‡•–‡†•ƒ’Ž‡•ˆ”‘–Š‡
    ƒ†‹—•ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ•–—†›ȋͲ͵͹͹ͺͻ͵ͳȌƒ†‡Ž‹‰‹„Ž‡•—„Œ‡ –•™‡”‡”ƒ†‘‹œ‡†‹ƒͳǣͳ
    ”ƒ–‹‘–‘‡‹–Š‡”‡Žƒ ‡•–”ƒ–‘”•–ƒ†ƒ”†‘ˆ ƒ”‡ȋȌ ‘•‹•–‹‰‘ˆˆ—Ž˜‡•–”ƒ–‘”ƒƒ”‘ƒ–ƒ•‡
    ‹Š‹„‹–‘”ƒ†•–”ƒ–‹ˆ‹‡†„›—–ƒ–‹‘•–ƒ–—•‘ˆESR1—•‹‰ —ƒ”†ƒ–͵͸Ͳšƒ†‘–Š‡” ”‹–‡”‹ƒ
    †‡• ”‹„‡†‹–Š‡ Ž‹‹ ƒŽ•–—†›’”‘–‘ ‘ŽǤ—„Œ‡ –•ˆ”‘–Š‡’”‹ƒ”›ͳͻͲͳǦ͵Ͳͺ”‡‰‹•–”ƒ–‹‘
    ’‘’—Žƒ–‹‘’‘•‹–‹˜‡ˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸Ͳš™‡”‡‹ Ž—†‡†‹–Š‡
    †‹ƒ‰‘•–‹ •–—†›’”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ › ‘Š‘”––‘ƒ••‡••–Š‡ Ž‹‹ ƒŽ˜ƒŽ‹†‹–›‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘
    ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•™‹–ŠESR1‹••‡•‡—–ƒ–‹‘•ˆ‘”̻
    ‡Žƒ ‡•–”ƒ–Ȍ –Š‡”ƒ’›Ǥ

    ͹ǤͳǤ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”EGFRš‘ͳͻ‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•


    Ž‹‹ ƒŽ–—†›‡•‹‰
    Š‡  Ž‹‹ ƒŽ•–—†›™ƒ•ƒ’Šƒ•‡ ǡ†‘—„Ž‡Ǧ„Ž‹†ǡ”ƒ†‘‹œ‡†•–—†›ƒ••‡••‹‰–Š‡‡ˆˆ‹ ƒ ›ƒ†
    •ƒˆ‡–›‘ˆ‘•‹‡”–‹‹„˜‡”•—••–ƒ†ƒ”†‘ˆ ƒ”‡ȋ‘ȌEGFR–›”‘•‹‡‹ƒ•‡‹Š‹„‹–‘”ȋ Ȍ–Š‡”ƒ’›
    ȋ‰‡ˆ‹–‹‹„‘”‡”Ž‘–‹‹„Ȍ‹–Š‡ˆ‹”•–ǦŽ‹‡–”‡ƒ–‡–‘ˆ’ƒ–‹‡–•™‹–ŠŽ‘ ƒŽŽ›ƒ†˜ƒ ‡†ƒ†‡–ƒ•–ƒ–‹ 
    ™Š‘•‡–—‘”•Šƒ˜‡EGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”‡š‘ʹͳͺͷͺ—–ƒ–‹‘•Ǥƒ–‹‡–•™‡”‡
    ‡”‘ŽŽ‡†„ƒ•‡†‘–Š‡’”‡•‡ ‡‘ˆEGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”‡š‘ʹͳͺͷͺ—–ƒ–‹‘•‹–Š‡‹”–—‘”
    ƒ•†‡–‡”‹‡†„›–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–ƒ–ƒ ‡–”ƒŽŽƒ„‘”ƒ–‘”›‘”–‡•–‹‰ƒ–ƒ Ǧ ‡”–‹ˆ‹‡†
    ‘”ƒ ”‡†‹–‡†Žƒ„‘”ƒ–‘”›ǤŠ‹• Ž‹‹ ƒŽ•–—†›™ƒ•—•‡†–‘•—’’‘”––Š‡ƒ’’”‘˜ƒŽ‘ˆ  —†‡”
    ʹͲͺͲ͸ͷ—’’Ž‡‡–ͺǤ
    —ƒ”†ƒ–͵͸ͲšEGFRš‘ͳͻ‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•”‹†‰‹‰–—†›‡•‹‰
    ”‡Ǧ–”‡ƒ–‡–„Ž‘‘†•ƒ’Ž‡•ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘’ƒ–‹‡–•’‘•‹–‹˜‡ˆ‘”EGFR—–ƒ–‹‘•„›
    –‹••—‡–‡•–‹‰”ƒ†‘‹œ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†›™‡”‡—•‡†–‘ƒ••‡••–Š‡•ƒˆ‡–›ƒ†
    ‡ˆˆ‡ –‹˜‡‡••‘ˆ —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆ’”‡˜‹‘—•Ž›—–”‡ƒ–‡†‡–ƒ•–ƒ–‹ ’ƒ–‹‡–•
    ™‹–ŠEGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•ˆ‘”  –Š‡”ƒ’›Ǥ

    ͵͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ”‡–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘ͳͺͻ ’ƒ–‹‡–•ȋ͵ͶΨ‘ˆ–Š‡”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘Ȍ™‡”‡
    –‡•–‡†™‹–Š —ƒ”†ƒ–͵͸Ͳƒ•’ƒ”–‘ˆƒ‡š’Ž‘”ƒ–‘”›ƒƒŽ›•‹•ǤŠ‹• —ƒ”†ƒ–͵͸Ͳ–‡•–‹‰–‘‘
    ’Žƒ ‡„‡ˆ‘”‡–Š‡†‹ƒ‰‘•–‹  Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›™ƒ•‹‹–‹ƒ–‡†Ǥ
    ŽŽ’ƒ–‹‡–•ƒ’Ž‡•™‘—Ž†‹†‡ƒŽŽ›Šƒ˜‡„‡‡–‡•–‡†—•‹‰ —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‹•†‹ƒ‰‘•–‹ •–—†›ǯ•
    ‡ˆˆ‹ ƒ ›ƒƒŽ›•‹•Ǥ ‘™‡˜‡”ǡ’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•™‡”‡‘Ž›ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–Š‡ʹͷʹ’ƒ–‹‡–•
    ȋͶͷΨ‘ˆ–Š‡”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘Ȍ‘–’”‡˜‹‘—•Ž›–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸ͲǤ
    Š‡—•‡‘ˆ–Š‹•’‘’—Žƒ–‹‘ƒŽ‘‡‹–Š‡†‹ƒ‰‘•–‹ •–—†›™ƒ•‘–ˆ‡ƒ•‹„Ž‡†—‡–‘–Š‡„‹ƒ•‹–”‘†— ‡†„›
    •‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•ˆ‘”‡š’Ž‘”ƒ–‘”›–‡•–‹‰Ǥ’‡ ‹ˆ‹ ƒŽŽ›ǡ’ƒ–‹‡–••‡Ž‡ –‡†ˆ‘”‡š’Ž‘”ƒ–‘”›–‡•–‹‰
    —•‹‰ —ƒ”†ƒ–͵͸Ͳ™‡”‡–Š‘•‡™Š‘Šƒ†’”‘‰”‡••‡†ƒ†Ȁ‘”†‹• ‘–‹—‡†–”‡ƒ–‡–ƒ––Š‡–‹‡‘ˆ
    •ƒ’Ž‡•‡Ž‡ –‹‘ˆ‘”–‡•–‹‰ǡ™Š‹ Š ”‡ƒ–‡†ƒ•‡Ž‡ –‹‘„‹ƒ•–Šƒ–‹•‡š’‡ –‡†–‘”‡•—Ž–‹Ž‘‰‡” ‹
    ’ƒ–‹‡–•–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸Ͳš”‡Žƒ–‹˜‡–‘–Š‘•‡–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸Ͳƒ†ǡ–Š‡”‡ˆ‘”‡ǡ
    ”‡Žƒ–‹˜‡–‘–Š‡ ”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘ƒ•ƒ™Š‘Ž‡Ǥ
    ‘”†‡”–‘‹‹‹œ‡–Š‹••‡Ž‡ –‹‘„‹ƒ•ǡ–Š‡†‹ƒ‰‘•–‹ •–—†›’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•‹ Ž—†‡•ƒŽŽ
    ’ƒ–‹‡–•™‹–Š’”‡–”‡ƒ–‡–’Žƒ•ƒƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–‡•–‹‰—•‹‰ —ƒ”†ƒ–͵͸Ͳšǡ
    •—’’Ž‡‡–‡†„›’ƒ–‹‡–•ˆ‘”™Š‘†ƒ–ƒ™ƒ•’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†‘ —ƒ”†ƒ–͵͸ͲǤŠ‹•
    ‘„‹‡†’ƒ–‹‡–‰”‘—’‹•‡š’‡ –‡†–‘”‡’”‡•‡––Š‡ˆ—ŽŽ”ƒ†‘‹œ‡†’ƒ–‹‡–’‘’—Žƒ–‹‘‹ƒ‘”‡
    ”‘„—•–ƒ‡”ǤŠ‡ƒƒŽ›–‹ ƒŽ ‘ ‘”†ƒ ‡•–—†›†‡• ”‹„‡†ƒ„‘˜‡ǡ•—’’Ž‡‡–‡†„›†‡‘•–”ƒ–‹‘
    ‘ˆ–Š‡ ‘’ƒ”ƒ„‹Ž‹–›‘ˆ‡›’‡”ˆ‘”ƒ ‡ Šƒ”ƒ –‡”‹•–‹ •ǡi.e.ǡ‘ƒ†’”‡ ‹•‹‘„‡–™‡‡–Š‡
    —ƒ”†ƒ–͵͸Ͳšƒ†ǡ™ƒ•’‡”ˆ‘”‡†–‘•—’’‘”––Š‡˜ƒŽ‹†‹–›‘ˆ ‘„‹‹‰†ƒ–ƒ‰‡‡”ƒ–‡†‘
    —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•ˆ‘”–Š‡†‡–‡ –‹‘‘ˆEGFRš‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ
    —–ƒ–‹‘•ȋ‡ˆ‡”–‘Section 6.12 Concordance - Guardant360 CDx Comparison to Guardant360
    LDT”‡•—Ž–•ȌǤŠ‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ–Š‡†‹• ‘”†ƒ ‡‘„•‡”˜‡†ˆ”‘–Š‡•‡•–—†‹‡•‘–Š‡
    ‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡†‡˜‹ ‡™ƒ•ˆ—”–Š‡”‡˜ƒŽ—ƒ–‡†–Š”‘—‰Š•‡•‹–‹˜‹–›ƒƒŽ›•‡•ȋ•‡‡„‡Ž‘™ȌǤ —”–Š‡”ƒ
    „Ž‘‘† ‘ŽŽ‡ –‹‘ ‘ ‘”†ƒ ‡•–—†›‡•–ƒ„Ž‹•Š‹‰–Š‡ ‘ ‘”†ƒ ‡„‡–™‡‡•ƒ’Ž‡• ‘ŽŽ‡ –‡†‹–”‡ 
    ‡ŽŽǦ ”‡‡•ƒ†–Š‡Ǧ•™ƒ• ‘†— –‡†–‘•—’’‘”––Š‡˜ƒŽ‹†‹–›‘ˆ–Š‡†ƒ–ƒ‰‡‡”ƒ–‡†„›
    –‡•–‹‰•ƒ’Ž‡• ‘ŽŽ‡ –‡†‹Ǧ•ȋ‡ˆ‡”–‘Section 6.13.a Blood Collection Tube
    Concordance Ǥ
    ‘’Žƒ•ƒˆ”‘ ’ƒ–‹‡–•‡‰ƒ–‹˜‡ˆ‘”EGFR—–ƒ–‹‘•„›–‹••—‡–‡•–‹‰™ƒ•ƒ˜ƒ‹Žƒ„Ž‡–‘
    ”‡’”‡•‡––Š‡ —ƒ”†ƒ–͵͸ͲǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’‘”–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲǦ’‘•‹–‹˜‡‹–‡†‡†
    —•‡’‘’—Žƒ–‹‘Ǥ••— Šǡ•—’’Ž‡‡–ƒŽƒ– Š‡†–‹••—‡ƒ†’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘–Š‡‘‹˜ƒ•‹˜‡˜•Ǥ
    ˜ƒ•‹˜‡—‰˜ƒŽ—ƒ–‹‘ Ž‹‹ ƒŽ•–—†›ȋ–Š‡ •–—†›ǡͲ͵͸ͳͷͶͶ͵Ȍ™‡”‡—•‡†–‘‡•–‹ƒ–‡–Š‡
    ’”‡˜ƒŽ‡ ‡‘ˆ’ƒ–‹‡–•’‘•‹–‹˜‡ˆ‘”EGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸Ͳ„—–
    ‡‰ƒ–‹˜‡„›–‹••—‡–‡•–‹‰–‘‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ–Š‹•’‘’—Žƒ–‹‘‘ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›Ǥ
    a. Bridging Study Inclusion and Exclusion Criteria
    x Inclusion Criteria for plasma samples from the FLAURA clinical study
    o ƒ–‹‡–• ”‡‡‡†ˆ‘”–Š‡  Ž‹‹ ƒŽ•–—†›™‹–Š†‘ —‡–‡†‹ˆ‘”‡† ‘•‡–ˆ‘”
    „Ž‘‘†•ƒ’Ž‡—•‡ˆ‘”†‹ƒ‰‘•–‹ †‡˜‡Ž‘’‡–
    o ”‡Ǧ–”‡ƒ–‡––‹‡’‘‹–’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–‡•–‹‰—•‹‰ —ƒ”†ƒ–͵͸Ͳ
    x Exclusion Criteria for plasma samples from the FLAURA clinical study
    o „•‡ ‡‘ˆ’Žƒ•ƒˆ‘”–‡•–‹‰‘ —ƒ”†ƒ–͵͸Ͳ
    o ˆ‘”‡† ‘•‡–™‹–Š†”ƒ™
    o Š‹ƒƒ‹Žƒ†’ƒ–‹‡–•

    ͵ͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    x Inclusion Criteria for samples from the NILE clinical study
    o ƒ–‹‡–‡”‘ŽŽ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†›™‹–Š†‘ —‡–‡†‹ˆ‘”‡† ‘•‡–
    o ”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–‡•–‹‰™‹–Š —ƒ”†ƒ–͵͸Ͳš
    o ˜ƒ‹Žƒ„‹Ž‹–›‘ˆ—•–ƒ‹‡†•Ž‹†‡•ƒ†Ȁ‘”ƒ–‹••—‡„Ž‘ ‘ˆˆ‘”ƒŽ‹Ǧˆ‹š‡†’ƒ”ƒˆˆ‹Ǧ‡„‡††‡†
    –‹••—‡™‹–Š•—ˆˆ‹ ‹‡––—‘” ‘–‡–ƒ†“—ƒ–‹–›ˆ‘”–‡•–‹‰ƒ•†‡ˆ‹‡†„›–Š‡ ‡–”ƒŽ
    –‡•–‹‰Žƒ„‘”ƒ–‘”›”‡“—‹”‡‡–•ˆ‘” ‘„ƒ•̺EGFR—–ƒ–‹‘‡•––‡•–‹‰Ǥ—‘”–‹••—‡—•–
    „‡ˆ”‘–Š‡•ƒ‡†‹•‡ƒ•‡’”‘ ‡••ƒ•–Š‡ •–—†›’Žƒ•ƒ•ƒ’Ž‡
    x Exclusion Criteria for samples from the NILE clinical study
    o „•‡ ‡‘ˆƒ˜ƒ‹Žƒ„Ž‡’Žƒ•ƒ‘”–‹••—‡ˆ‘” —ƒ”†ƒ–͵͸Ͳšƒ† ‘„ƒ• ̺EGFR—–ƒ–‹‘‡•–
    –‡•–‹‰ǡ”‡•’‡ –‹˜‡Ž›
    o ˆ‘”‡† ‘•‡–™‹–Š†”ƒ™
    b. Follow-up Schedule
    Š‡ —ƒ”†ƒ–͵͸ͲšEGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•„”‹†‰‹‰•–—†›‹˜‘Ž˜‡†‘Ž›
    ”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ’Žƒ•ƒ•ƒ’Ž‡•Ǣƒ••— Šǡ‘ƒ††‹–‹‘ƒŽ’ƒ–‹‡–ˆ‘ŽŽ‘™Ǧ—’™ƒ• ‘†— –‡†Ǥ
    c. Clinical Endpoints
    Š‡ Ž‹‹ ƒŽ‡†’‘‹–—•‡†–‘ƒ••‡••‘•‹‡”–‹‹„‡ˆˆ‹ ƒ ›‹–Š‡  Ž‹‹ ƒŽ•–—†›’”‹ƒ”›
    ‘„Œ‡ –‹˜‡™ƒ•‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡†’”‘‰”‡••‹‘Ǧˆ”‡‡•—”˜‹˜ƒŽȋ Ȍǡ™Š‹ Š™ƒ•†‡ˆ‹‡†ƒ•–Š‡–‹‡
    ‹–‡”˜ƒŽ„‡–™‡‡”ƒ†‘‹œƒ–‹‘ƒ†–Š‡ˆ‹”•– ’”‘‰”‡••‹‘‘”‘”–ƒŽ‹–›‡˜‡–ǤŠ‡
    —ƒ”†ƒ–͵͸ͲšEGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•„”‹†‰‹‰•–—†›—•‡•–Š‡•ƒ‡ Ž‹‹ ƒŽ
    ‡†’‘‹–ˆ‘”‹–•’”‹ƒ”›‘„Œ‡ –‹˜‡Ǥ
    x Diagnostic Objective and Endpoint
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†›™ƒ•–‘†‡‘•–”ƒ–‡–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ
    –Š‡ —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆ‡–ƒ•–ƒ–‹ ’ƒ–‹‡–•™‹–ŠEGFR‡š‘ͳͻ†‡Ž‡–‹‘•
    ‘”ͺͷͺ—–ƒ–‹‘•ˆ‘”–”‡ƒ–‡–™‹–Š  ǤŠ‹•‘„Œ‡ –‹˜‡™ƒ•ƒ••‡••‡†„› ‘’ƒ”‹‰–Š‡
    ‡ˆˆ‹ ƒ ›ǡ –‘ ˜ͳǤͳ„›‹˜‡•–‹‰ƒ–‘”ƒ••‡••‡–ǡ‘ˆ•‹‰Ž‡Ǧƒ‰‡–   ‘’ƒ”‡†™‹–Š
    ‘EGFR –Š‡”ƒ’›‹–Š‡–‹••—‡Ǧ’‘•‹–‹˜‡ǡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡’ƒ–‹‡–•‡”‘ŽŽ‡†‹
    Ǥ
    Š‡’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆ–‹••—‡Ǧ‡‰ƒ–‹˜‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡’ƒ–‹‡–•‹–Š‡‡ˆˆ‡ –‹˜‡‡••
    ‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš™ƒ•ƒ••‡••‡†–Š”‘—‰Šƒ•‡•‹–‹˜‹–›ƒƒŽ›•‹•Ǥ•‘’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘
    ’ƒ–‹‡–•‡‰ƒ–‹˜‡ˆ‘”EGFR—–ƒ–‹‘•„›–‹••—‡–‡•–‹‰™‡”‡ƒ˜ƒ‹Žƒ„Ž‡–‘”‡’”‡•‡––Š‡
    —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’‘”–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡‹–‡†‡†—•‡
    ’‘’—Žƒ–‹‘ǡ•ƒ’Ž‡•ˆ”‘–Š‡  Ž‹‹ ƒŽ•–—†›™‡”‡–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡
    ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–—•‹‰–‹••—‡–‘ ƒŽ —Žƒ–‡–Š‡ˆ‘”–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•–‘
    ‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ–Š‹•’‘’—Žƒ–‹‘‘ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›ǤŠ‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ•
    ’‡”ˆ‘”‡†—•‹‰†ƒ–ƒ‰‡‡”ƒ–‡†„›ƒƒŽ›œ‹‰•—’’Ž‡‡–ƒŽ–‹••—‡•ƒ’Ž‡•ˆ”‘–Š‡  Ž‹‹ ƒŽ
    •–—†›—•‹‰–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–ƒ†„›ƒƒŽ›œ‹‰”‡•‹†—ƒŽ’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘–Š‘•‡
    •ƒ‡’ƒ–‹‡–•—•‹‰ —ƒ”†ƒ–͵͸ͲšǤ
     ‘—–ƒ„‹Ž‹–›‘ˆ‘Š‘”–
    Š‡ †‹ƒ‰‘•–‹ •–—†›‹ Ž—†‡†ͶͶͳ‘ˆ–Š‡–‘–ƒŽͷͷ͸ȋ͹ͻǤ͵ΨȌ’ƒ–‹‡–•”ƒ†‘‹œ‡†‹–Š‡
     Ž‹‹ ƒŽ•–—†›ȋFigure 2ȌǤŠ‡ƒƒŽ›•‹••‡–• ‘’”‹•‡†‹ƒ‰‘•–‹ †ƒ–ƒ‰‡‡”ƒ–‡†—•‹‰
    —ƒ”†ƒ–͵͸ͲšȋʹͷʹȀͶͶͳǡͷ͹ǤͳΨȌ•—’’Ž‡‡–‡†„›†ƒ–ƒ’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†‘ —ƒ”†ƒ–͵͸Ͳ

    ͵ͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ȋͳͺͻȀͶͶͳǡͶʹǤͻΨȌƒ•†‡• ”‹„‡†ƒ„‘˜‡Ǥ ‡”‡ƒˆ–‡”ǡ —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•”‡•—Ž–•
    ‘„‹‡†ƒ”‡”‡ˆ‡””‡†–‘ƒ• —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•Ǥ
    ˆ–Š‡•‡ǡ͵ͲͶ’ƒ–‹‡–•ȋͷͶǤ͹Ψ‘ˆ–Š‡–‘–ƒŽ’‘’—Žƒ–‹‘Ȍ–‡•–‡†’‘•‹–‹˜‡„›–Š‡ —ƒ”†ƒ–͵͸Ͳ™‡”‡
    ‹ Ž—†‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹••‡–ǡ™Š‹Ž‡ͳͳͲȋʹͶǤͻΨȌ–‡•–‡†‡‰ƒ–‹˜‡ǡƒ†ʹ͹ȋ͸ǤͳΨȌ
    ˆƒ‹Ž‡†–‡•–‹‰Ǥ

    
    Figure 2. Guardant360 CDx EGFR Exon 19 Deletions or L858R Mutations Bridging Study Patient
    Accountability and Analysis Set Definitions
    –—†›‘’—Žƒ–‹‘‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡ƒ”ƒ‡–‡”•
    ‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•‡”‘ŽŽ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†›
    ȋ Ȍ™‡”‡ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡–‘–Š‡ —ƒ”†ƒ–͵͸ͲšEGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•
    „”‹†‰‹‰•–—†›’‘’—Žƒ–‹‘•ƒ•†‡ˆ‹‡†„› —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•ȋ‰Ȍƒ†ƒ••‡••‡†ˆ‘”–”‡ƒ–‡–
    ƒ”„ƒŽƒ ‡Ǥ••Š‘™‹Table 30ǡ†‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‹–Š‡ Ž‹‹ ƒŽ
    ‡ˆˆ‹ ƒ ›ƒƒŽ›•‹••—„‰”‘—’•™‡”‡™‡ŽŽǦ„ƒŽƒ ‡†„‡–™‡‡–”‡ƒ–‡–ƒ”•ǡƒ‹–ƒ‹‹‰ƒ’’”‘š‹ƒ–‡Ž›
    ƒͳǣͳ”ƒ†‘‹œƒ–‹‘™‹–Š‹‡ƒ Š‰”‘—’Ǥ

    Table 30. Clinical Effectiveness Analysis Subgroup Demographics and Baseline Clinical
    Characteristics
    gCEAS FAS
    EGFR TKI EGFR TKI
    (gefitinib or (gefitinib or
    TAGRISSO erlotinib) TAGRISSO erlotinib)
    Characteristic (n=146) (n=158) (n=279) (n=277)
    ‰‡ȋ›‡ƒ”•Ȍ ‡†‹ƒȋ”ƒ‰‡Ȍ ͸͵ȋ͵ʹǦͺ͵Ȍ ͸͵ȋ͵ͷǦͺ͹Ȍ ͸Ͷȋʹ͸ǦͺͷȌ ͸Ͷȋ͵ͷǦͻ͵Ȍ
    ‰‡‰”‘—’ δ͸ͷ ͺͳȋͷͷǤͷȌ ͻʹȋͷͺǤʹȌ ͳͷ͵ȋͷͶǤͺȌ ͳͶʹȋͷʹǤ͵Ȍ
    ȋ›‡ƒ”•ȌǡȋΨȌ η͸ͷ ͸ͷȋͶͶǤͷȌ ͸͸ȋͶͳǤͺȌ ͳʹ͸ȋͶͷǤʹȌ ͳ͵ʹȋͶ͹Ǥ͹Ȍ
    ‡šǡȋΨȌ ‡ƒŽ‡ ͻͷȋ͸ͷǤͳȌ ͳͲ͵ȋ͸ͷǤʹȌ ͳ͹ͺȋ͸͵ǤͺȌ ͳ͹ʹȋ͸ʹǤͳȌ
    ƒ ‡ǡȋΨȌ •‹ƒ ͺ͵ȋͷ͸ǤͺȌ ͻͶȋͷͻǤͷȌ ͳ͹Ͷȋ͸ʹǤͶȌ ͳ͹͵ȋ͸ʹǤͷȌ
    ‘‹‰ ‡˜‡” ͻͻȋ͸͹ǤͺȌ ͳͲͲȋ͸͵Ǥ͵Ȍ ͳͺʹȋ͸ͷǤʹȌ ͳ͹ͷȋ͸͵ǤʹȌ
    •–ƒ–—•ǡȋΨȌ —””‡– ͳȋͲǤ͹Ȍ ͶȋʹǤͷȌ ͺȋʹǤͻȌ ͻȋ͵ǤʹȌ
    ‘”‡” Ͷ͸ȋ͵ͳǤͷȌ ͷͶȋ͵ͶǤʹȌ ͺͻȋ͵ͳǤͻȌ ͻ͵ȋ͵͵Ǥ͸Ȍ
    ͶͲ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    gCEAS FAS
    EGFR TKI EGFR TKI
    (gefitinib or (gefitinib or
    TAGRISSO erlotinib) TAGRISSO erlotinib)
    Characteristic (n=146) (n=158) (n=279) (n=277)
     •–ƒ‰‹‰ Ǧ  ͳͷȋͳͲǤ͵Ȍ ͳͷȋͻǤͷȌ ͷʹȋͳͺǤ͸Ȍ Ͷ͹ȋͳ͹ǤͲȌ
    ƒ–†‹ƒ‰‘•‹•  ͳ͵ͳȋͺͻǤ͹Ȍ ͳͶ͵ȋͻͲǤͷȌ ʹʹ͸ȋͺͳǤͲȌ ʹ͵Ͳȋͺ͵ǤͲȌ
    ‘™ ͲȋͲȌ ͲȋͲȌ ͳȋͲǤͶȌ ͲȋͲȌ
    ˜‡”ƒŽŽ ‡–ƒ•–ƒ–‹  ͳͶͳȋͻ͸Ǥ͸Ȍ ͳͷͷȋͻͺǤͳȌ ʹ͸ͶȋͻͶǤ͸Ȍ ʹ͸ʹȋͻͶǤ͸Ȍ
    †‹•‡ƒ•‡ ‘ ƒŽŽ›ƒ†˜ƒ ‡† ͶȋʹǤ͹Ȍ ͵ȋͳǤͻȌ ͳͶȋͷǤͲȌ ͳͷȋͷǤͶȌ
    Žƒ••‹ˆ‹ ƒ–‹‘ ‹••‹‰ ͳȋͲǤ͹Ȍ Ͳ Ͳ Ȍ ͳȋͲǤͶȌ Ͳ Ͳ Ȍ
    ‹•–‘Ž‘‰› †‡‘ ƒ” ‹‘ƒ ͳ͵͹ȋͻ͵ǤͺȌ ͳͶͷȋͻͳǤͺȌ ʹͶ͸ȋͺͺǤʹȌ ʹͷͳȋͻͲǤ͸Ȍ
    –›’‡ –Š‡” ͻȋ͸ǤʹȌ ͳ͵ȋͺǤʹȌ ͵͵ȋͳͳǤͺȌ ʹ͸ȋͻǤͶȌ

    ‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•‡”‘ŽŽ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†›ǡ
    ˆ—ŽŽƒƒŽ›•‹••‡–ȋ Ȍǡ™‡”‡ƒŽ•‘ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡ ’ƒ–‹‡–•™‹–Š’Žƒ•ƒƒ˜ƒ‹Žƒ„Ž‡ˆ‘”
    –‡•–‹‰‹–Š‹•†‹ƒ‰‘•–‹ •–—†›ȋ‰Ȍƒ†–Š‘•‡™‹–Š‘—–ȋ‰Ȍ–‘‡˜ƒŽ—ƒ–‡ ‘’ƒ”ƒ„‹Ž‹–›ȋ Table 31 Ǥ
    ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •™‡”‡™‡ŽŽǦ„ƒŽƒ ‡†™‹–Š‹‡ƒ Š’‘’—Žƒ–‹‘„›–”‡ƒ–‡–ƒ”ˆ‘”ƒŽŽ
    †‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •Ǥ
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •„‡–™‡‡‰ƒ†‰™‡”‡™‡ŽŽǦ„ƒŽƒ ‡†™‹–Š–Š‡
    ‡š ‡’–‹‘‘ˆƒ‰‡η͸ͷȋͶͺǤ͵Ψ‰˜•Ǥ͵ͻǤͳΨ‰ǡ’αͲǤͲ͹ͻͳȌǡ‡˜‡”•‘‹‰•–ƒ–—•ȋ͸ʹǤͺΨ‰˜•Ǥ
    ͸ͻǤ͸Ψ‰ǡ’αͲǤͳ͹ͺͷȌǡ •–ƒ‰‡ƒ–†‹ƒ‰‘•‹• Ǧ ȋͳ͸ǤͳΨ‰˜•ǤʹͶǤ͵Ψ‰ǡ’αͲǤͲ͵ͷͶȌǡƒ†
    ‡–ƒ•–ƒ–‹ ‘˜‡”ƒŽŽ†‹•‡ƒ•‡ Žƒ••‹ˆ‹ ƒ–‹‘ȋͻͷǤͷΨ‰˜•ǤͻͳǤ͵Ψ‰ǡ’αͲǤͲ͸Ͳ͵ȌǤ

    Table 31. Comparison of Demographics and Baseline Clinical Characteristics Between FLAURA
    Patients with Plasma Available for Testing (gAS) and Those Without (gNT)
    gAS gNT
    2-sided
    TAGRISSO EGFR TKI Total TAGRISSO EGFR TKI Total p value
    Characteristics (n=219) (n=222) (n=441) (n=60) (n=55) (n=115) [a]
    ‰‡‰”‘—’ δ͸ͷ ͳͳʹȋͷͳǤͳȌ ͳͳ͸ȋͷʹǤ͵Ȍ ʹʹͺȋͷͳǤ͹Ȍ Ͷͳȋ͸ͺǤ͵Ȍ ʹͻȋͷʹǤ͹Ȍ ͹Ͳ ͲǤͲ͹ͻͳ
    ȋ›‡ƒ”•Ȍǡ ȋ͸ͲǤͻȌ
    ȋΨȌ η͸ͷ ͳͲ͹ȋͶͺǤͻȌ ͳͲ͸ȋͶ͹Ǥ͹Ȍ ʹͳ͵ȋͶͺǤ͵Ȍ ͳͻȋ͵ͳǤ͹Ȍ ʹ͸ȋͶ͹Ǥ͵Ȍ Ͷͷ
    ȋ͵ͻǤͳȌ
    ‡šǡȋΨȌ ‡ƒŽ‡ ͳ͵͹ȋ͸ʹǤ͸Ȍ ͳͶʹȋ͸͵ǤͷȌ ʹ͹ͻȋ͸͵Ǥ͵Ȍ Ͷͳȋ͸ͺǤ͵Ȍ ͵ͲȋͷͶǤͷȌ ͹ͳ ͲǤ͹͸ʹͺ
    ȋ͸ͳǤ͹Ȍ
    ƒ ‡ǡȋΨȌ •‹ƒ ͳ͵͹ȋ͸ʹǤ͸Ȍ ͳͶͳȋ͸͵ǤͷȌ ʹ͹ͺȋ͸͵ǤͲȌ ͵͹ȋ͸ͳǤ͹Ȍ ͵ʹȋͷͺǤʹȌ ͸ͻ ͲǤͷͳͳ͹
    ȋ͸ͲǤͲȌ
    ‘‹‰ ‡˜‡” ͳ͵͹ȋ͸ʹǤ͸Ȍ ͳͶͲȋ͸͵ǤͳȌ ʹ͹͹ȋ͸ʹǤͺȌ Ͷͷȋ͹ͷǤͲȌ ͵ͷȋ͸͵Ǥ͸Ȍ ͺͲ ͲǤͳ͹ͺͷ
    •–ƒ–—• ȋ͸ͻǤ͸Ȍ
    —””‡–Ȁ ͺʹȋ͵͹ǤͶȌ ͺʹȋ͵͸ǤͻȌ ͳ͸Ͷȋ͵͹ǤʹȌ ͳͷȋʹͷǤͲȌ ʹͲȋ͵͸ǤͶȌ ͵ͷ
    ‘”‡” ȋ͵ͲǤͶȌ
     •–ƒ‰‡ƒ– Ǧ  ͵ͺȋͳ͹ǤͶȌ ͵͵ȋͳͶǤͻȌ ͹ͳȋͳ͸ǤͳȌ ͳͶȋʹ͵Ǥ͵Ȍ ͳͶȋʹͷǤͷȌ ʹͺ ͲǤͲ͵ͷͶ
    †‹ƒ‰‘•‹• ȋʹͶǤ͵Ȍ
     ͳͺͳȋͺʹǤ͸Ȍ ͳͺͻȋͺͷǤͳȌ ͵͹Ͳȋͺ͵ǤͻȌ Ͷͷȋ͹ͷǤͲȌ Ͷͳȋ͹ͶǤͷȌ ͺ͸
    ȋ͹ͶǤͺȌ
    ‹••‹‰ Ͳ Ͳ Ͳ ͳȋͳǤ͹Ȍ Ͳ ͳȋͲǤͻȌ

    Ͷͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    gAS gNT
    2-sided
    TAGRISSO EGFR TKI Total TAGRISSO EGFR TKI Total p value
    Characteristics (n=219) (n=222) (n=441) (n=60) (n=55) (n=115) [a]
    ˜‡”ƒŽŽ ‡–ƒ•–ƒ–‹  ʹͲͺȋͻͷǤͲȌ ʹͳ͵ȋͻͷǤͻȌ ͶʹͳȋͻͷǤͷȌ ͷ͸ȋͻ͵Ǥ͵Ȍ ͶͻȋͺͻǤͳȌ ͳͲͷ ͲǤͲ͸Ͳ͵
    †‹•‡ƒ•‡ ȋͻͳǤ͵Ȍ
    Žƒ••‹ˆ‹ ƒ–‹‘ ‘ ƒŽŽ› ͳͲȋͶǤ͸Ȍ ͻȋͶǤͳȌ ͳͻȋͶǤ͵Ȍ Ͷȋ͸Ǥ͹Ȍ ͸ȋͳͲǤͻȌ ͳͲȋͺǤ͹Ȍ
    ƒ†˜ƒ ‡†
    ‹••‹‰ ͳȋͲǤͷȌ Ͳ ͳȋͲǤʹȌ Ͳ Ͳ Ͳ
    ‹•–‘Ž‘‰› †‡‘ ƒ” ‹Ǧ ʹͲͻȋͻͷǤͶȌ ʹͲͶȋͻͳǤͻȌ Ͷͳ͵ȋͻ͵Ǥ͹Ȍ ͷ͸ȋͻ͵Ǥ͵Ȍ ͷͶȋͻͺǤʹȌ ͳͳͲ ͲǤͶͳͺͷ
    –›’‡ ‘ƒ ȋͻͷǤ͹Ȍ
    –Š‡” –Š‡” ͳͲȋͶǤ͸Ȍ ͳͺȋͺǤͳȌ ʹͺȋ͸Ǥ͵Ȍ Ͷȋ͸Ǥ͹Ȍ ͳȋͳǤͺȌ ͷȋͶǤ͵Ȍ
    ȏƒȐʹǦ•‹†‡†’Ǧ˜ƒŽ—‡‹•„ƒ•‡†‘Š‹Ǧ•“—ƒ”‡–‡•–ˆ‘”–Š‡ ‘’ƒ”‹•‘•Ǥ–ƒ–‹•–‹ ƒŽ ‘’ƒ”‹•‘‹•„ƒ•‡†‘‘Ǧ‹••‹‰˜ƒŽ—‡•Ǥ
    Table 32•Š‘™•–Šƒ–†‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•• ”‡‡‡†ˆ‘”–Š‡
    ƒ†‡”‘ŽŽ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†‹‡•™‡”‡™‡ŽŽǦ„ƒŽƒ ‡†„‡–™‡‡–Š‡•—„‰”‘—’•—•‡†‹
    –Š‡•—’’Ž‡‡–ƒ”› —ƒ”†ƒ–͵͸ͲǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’”‡˜ƒŽ‡ ‡ƒƒŽ›•‹•™‹–Š–Š‡‡š ‡’–‹‘‘ˆ
    ”ƒ ‡ƒ†•‘‹‰•–ƒ–—•Ǥ

    Table 32. Supplementary Guardant360-Positive, Tissue-Negative Prevalence Analysis


    Subgroup Demographics and Baseline Clinical Characteristics
    FLAURA Patients
    FAS Screen Failure Total NILE Patients
    Characteristic (n=556) (n=438) (n=994) (n=92)
    ‰‡ ”‘—’ δ͸ͷ ʹͻͺȋͷ͵Ǥ͸Ȍ ʹͶͻȋͷ͸ǤͺȌ ͷͶ͹ȋͷͷǤͲȌ ͶͲȋͶ͵ǤͷȌ
    ȋ›‡ƒ”•ȌǡȋΨȌ η͸ͷ ʹͷͺȋͶ͸ǤͶȌ ͳͺͻȋͶ͵ǤʹȌ ͶͶ͹ȋͶͷǤͲȌ ͷʹȋͷ͸ǤͷȌ
    ‡šǡȋΨȌ ‡ƒŽ‡ ͵ͷͲȋ͸ʹǤͻȌ ʹʹͺȋͷʹǤͳȌ ͷ͹ͺȋͷͺǤͳȌ ͷ͹ȋ͸ʹǤͲȌ
    ƒ ‡ǡȋΨȌ •‹ƒ ͵Ͷ͹ȋ͸ʹǤͶȌ ʹʹͳȋͷͲǤͷȌ ͷ͸ͺȋͷ͹ǤͳȌ ͷȋͷǤͶȌ
    ‘‹‰–ƒ–—• ‡˜‡” ͵ͷ͹ȋ͸ͶǤʹȌ ʹͷͳȋͷ͹Ǥ͵Ȍ ͸Ͳͺȋ͸ͳǤʹȌ ʹͳȋʹʹǤͺȌ
    —””‡– ͳ͹ȋ͵ǤͳȌ ͷ͹ȋͳ͵ǤͲȌ ͹Ͷȋ͹ǤͶȌ ʹʹȋʹ͵ǤͻȌ
    ‘”‡” ͳͺʹȋ͵ʹǤ͹Ȍ ͳ͵ͲȋʹͻǤ͹Ȍ ͵ͳʹȋ͵ͳǤͶȌ Ͷ͸ȋͷͲǤͲȌ
    ‹••‹‰ Ͳ Ͳ Ͳ ͵ȋ͵Ǥ͵Ȍ
     •–ƒ‰‹‰ƒ– Ǧ  ͻͻȋͳ͹ǤͺȌ Ͳ ͻͻȋͳͲǤͲȌ ͳ͹ȋͳͺǤͷȌ
    †‹ƒ‰‘•‹•  Ͷͷ͸ȋͺʹǤͲȌ Ͳ Ͷͷ͸ȋͶͷǤͻȌ ͹ͷȋͺͳǤͷȌ
    ‹••‹‰ ͳȋͲǤʹȌ Ͷ͵ͺȋͳͲͲȌ Ͷ͵ͻȋͶͶǤʹȌ Ͳ
    ˜‡”ƒŽŽ†‹•‡ƒ•‡ ‡–ƒ•–ƒ–‹  ͷʹ͸ȋͻͶǤ͸Ȍ Ͳ ͷʹ͸ȋͷʹǤͻȌ ͺͻȋͻ͸Ǥ͹Ȍ
    Žƒ••‹ˆ‹ ƒ–‹‘ ‘ ƒŽŽ›ƒ†˜ƒ ‡† ʹͻȋͷǤʹȌ Ͳ ʹͻȋʹǤͻȌ ͵ȋ͵Ǥ͵Ȍ
    ‹••‹‰ ͳȋͲǤʹȌ Ͷ͵ͺȋͳͲͲȌ Ͷ͵ͻȋͶͶǤʹȌ Ͳ
    ‹•–‘Ž‘‰›–›’‡ †‡‘ ƒ” ‹‘ƒ ͷʹ͵ȋͻͶǤͳȌ Ͳ ͷʹ͵ȋͷʹǤ͸Ȍ ͺͺȋͻͷǤ͹Ȍ
    –Š‡” ͵͵ȋͷǤͻȌ Ͳ ͵͵ȋ͵Ǥ͵Ȍ ͶȋͶǤ͵Ȍ
    ‹••‹‰ Ͳ Ͷ͵ͺȋͳͲͲȌ Ͷ͵ͺȋͶͶǤͳȌ Ͳ

    ƒˆ‡–›ƒ†ˆˆ‡ –‹˜‡‡••‡•—Ž–•
    a. Safety Results
    ƒ–ƒ”‡‰ƒ”†‹‰–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‹ ƒ ›‘ˆ  –Š‡”ƒ’›™‡”‡’”‡•‡–‡†‹–Š‡‘”‹‰‹ƒŽ†”—‰
    ƒ’’”‘˜ƒŽƒ†ƒ”‡•—ƒ”‹œ‡†‹–Š‡†”—‰Žƒ„‡ŽǤ‡ˆ‡”–‘–Š‡  Žƒ„‡Žˆ‘”‘”‡‹ˆ‘”ƒ–‹‘Ǥ‘
    ƒ†˜‡”•‡‡˜‡–•™‡”‡”‡’‘”–‡†‹–Š‡ ‘†— –‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†‹‡•ƒ•–Š‡•‡‹˜‘Ž˜‡†”‡–”‘•’‡ –‹˜‡
    –‡•–‹‰‘ˆ„ƒ‡†•’‡ ‹‡•‘Ž›Ǥ

    Ͷʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    b. Effectiveness Results
    ‹Ǥ  ‹ƒ–‹‡–•‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳˆ‘”EGFRš‘ͳͻ‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•
    Š‡‡ˆˆ‹ ƒ ›‘ˆ•‹‰Ž‡Ǧƒ‰‡–  ”‡Žƒ–‹˜‡–‘EGFR –Š‡”ƒ’›‹’ƒ–‹‡–•”ƒ†‘‹œ‡†‹
    ’‘•‹–‹˜‡ˆ‘”EGFR‡š‘ͳͻ†‡Ž‡–‹‘•‘”ͺͷͺ—–ƒ–‹‘•„›–‹••—‡ƒ†„› —ƒ”†ƒ–͵͸Ͳ
    ȋ‰Ȍ‹••Š‘™‹Table 33ǤŠ‡‘„•‡”˜‡† Šƒœƒ”†”ƒ–‹‘ȋ Ȍ‘ˆͲǤͶͳȋͻͷΨ ͲǤ͵ͳǡͲǤͷͶ ‹•
    •‹‹Žƒ”–‘–Šƒ–ˆ‘”–Š‡ˆ—ŽŽ ”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘ȋ ǡ  ͲǤͶ͸ǡͻͷΨ ͲǤ͵͹ǡͲǤͷ͹ȌǤ
    Š‡ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›‘„•‡”˜‡†‹–Š‡–‹••—‡ƒ†’Žƒ•ƒ’‘•‹–‹˜‡’‘”–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳ
    ‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǡ‰ǡ‹• ‘•‹•–‡–™‹–Š–Šƒ–‹–Š‡ Ǥ
    ƒ’ŽƒǦ‡‹‡”ƒƒŽ›•‹•‘ˆ ‹–Š‡‰‹•’”‡•‡–‡†‹Figure 3Ǥ

    Table 33. Investigator-Assessed PFS in the gCEAS and FAS


     Comparison between treatments
    Number (%) of Hazard Ratio
    Population Treatment N patients with events [a] (95% CI) 2-sided p-value
    ‰ȏ„Ȑ    ͳͶ͸ ͺ͵ȋͷ͸ǤͺȌ
    ͲǤͶͳȋͲǤ͵ͳǡͲǤͷͶ  δͲǤͲͲͲͳ
    EGFR  ͳͷͺ ͳ͵ʹȋͺ͵ǤͷȌ
    ȏ„Ȑ    ʹ͹ͻ ͳ͵͸ȋͶͺǤ͹Ȍ
    ͲǤͶ͸ȋͲǤ͵͹ǡͲͷ͹Ȍ δͲǤͲͲͲͳ
    EGFR  ʹ͹͹ ʹͲ͸ȋ͹ͶǤͶȌ
    ȏƒȐ”‘‰”‡••‹‘‡˜‡–•–Šƒ–†‘‘–‘ —”™‹–Š‹ʹ• Š‡†—Ž‡†˜‹•‹–•ȋ’Ž—•˜‹•‹–™‹†‘™Ȍ‘ˆ–Š‡Žƒ•–‡˜ƒŽ—ƒ„Ž‡ƒ••‡••‡–ȋ‘”
    ”ƒ†‘‹œƒ–‹‘Ȍƒ”‡ ‡•‘”‡†ƒ†–Š‡”‡ˆ‘”‡‡š Ž—†‡†‹–Š‡—„‡”‘ˆ‡˜‡–•Ǥ”‘‰”‡••‹‘‹ Ž—†‡•†‡ƒ–Š•‹–Š‡ƒ„•‡ ‡
    ‘ˆ ȋ˜ͳǤͳȌ’”‘‰”‡••‹‘Ǥ
    ȏ„ȐŠ‡ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†—•‹‰ƒŽ‘‰”ƒ–‡•–•–”ƒ–‹ˆ‹‡†„›—–ƒ–‹‘•–ƒ–—•ƒ†”ƒ ‡ǤŠƒœƒ”†”ƒ–‹‘δͳˆƒ˜‘”•
      

    Ͷ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    
    Figure 3. Kaplan-Meier Plot of Investigator-Assessed PFS for the gCEAS
    ‹‹Ǥ ‡•‹–‹˜‹–›ƒŽ›•‹•
    ’—–ƒ–‹‘‘ˆ‹••‹‰ —ƒ”†ƒ–͵͸Ͳ‡•–‡•—Ž–•”‹ƒ”›ƒŽ›•‹•ˆ‘”–Š‡‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡†
     
    Š‡”‘„—•–‡••‘ˆ–Š‡•–—†› ‘ Ž—•‹‘•™ƒ•ƒ••‡••‡†„›‡˜ƒŽ—ƒ–‹‰–Š‡‹’ƒ –‘ˆ‹••‹‰
    —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•‘–Š‡‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡†‡˜‹ ‡ǤŠ‡‹••‹‰ —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•™‡”‡
    ‹’—–‡†‹–Š‡”ƒ†‘‹œ‡†ȋ–‹••—‡’‘•‹–‹˜‡Ȍ’‘’—Žƒ–‹‘—•‹‰ƒ‹’—–ƒ–‹‘‘†‡Ž—†‡”‹••‹‰
    ƒ–”ƒ†‘ƒ••—’–‹‘Ǥ
    Š‡”‡™‡”‡ͳͳͷ‘—–‘ˆͷͷ͸ȋʹͳΨȌ”ƒ†‘‹œ‡†’ƒ–‹‡–•‹ ™‹–Š‘—– —ƒ”†ƒ–͵͸Ͳ–‡•–
    ”‡•—Ž–•Ǥ‡‘ˆ–Š‡ͳͳͷ’ƒ–‹‡–•Šƒ†‹••‹‰„ƒ•‡Ž‹‡ ‘˜ƒ”‹ƒ–‡•ƒ†‹•–Š‡”‡ˆ‘”‡”‡‘˜‡†ˆ”‘–Š‡
    ƒƒŽ›•‹•ƒ•–Š‹•’ƒ–‹‡–ǯ•’”‘„ƒ„‹Ž‹–› —ƒ”†ƒ–͵͸Ͳ’‘•‹–‹˜‡ȋ ͵͸ͲΪȌ ‘—Ž†‘–„‡’”‡†‹ –‡†ˆ”‘
    –Š‡•‡Ž‡ –‡†‘†‡ŽǤƒ•‡Ž‹‡ ‘˜ƒ”‹ƒ–‡•‹ Ž—†‡†‹–Š‡‘‰‹–‘†‡Ž™‡”‡ǣ
    x  ȋ‹‘–Š•ǡ’‘•–Ǧ„ƒ•‡Ž‹‡†ƒ–ƒȌ
    x ‰‡‰”‘—’ȋδ͸ͷ›‡ƒ”•ǡη͸ͷ›‡ƒ”•Ȍ
    x ‘‹‰•–ƒ–—•ȋ‡˜‡”ǡ —””‡–Ȁˆ‘”‡”Ȍ
    x  •–ƒ‰‡ƒ–†‹ƒ‰‘•‹•ȋ Ǧ ǡ Ȍ
    x ˜‡”ƒŽŽ†‹•‡ƒ•‡ Žƒ••‹ˆ‹ ƒ–‹‘ȋ‡–ƒ•–ƒ–‹ ǡŽ‘ ƒŽŽ›ƒ†˜ƒ ‡†Ȍ
    x ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–—•‹‰’Žƒ•ƒ–‡•–”‡•—Ž–ȋ’‘•‹–‹˜‡ǡ‡‰ƒ–‹˜‡ǡˆƒ‹Ž—”‡ǡ‹••‹‰Ȍ
    ‡•—Ž–•„ƒ•‡†‘ͳǡͲͲͲ‹’—–ƒ–‹‘•ƒ”‡’”‡•‡–‡†‹Table 34™Š‹ Š•Š‘™•”‘„—•–ƒ† ‘•‹•–‡–
      „‡‡ˆ‹–‹„‘–Š–Š‡‰†‡ˆ‹‡†„›‡š‹•–‹‰ —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•ƒ†–Š‡‰
    ȋ‘„•‡”˜‡†ƒ†‹’—–‡†Ȍǡ‹™Š‹ Š‹••‹‰ —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•™‡”‡‹’—–‡†˜‹ƒ–Š‡
    •’‡ ‹ˆ‹‡†‘‰‹–‘†‡ŽǤŠ‡•‡”‡•—Ž–•†‡‘•–”ƒ–‡–Šƒ––Š‡‹••‹‰†ƒ–ƒŠƒ•‘‡ƒ‹‰ˆ—Ž‹’ƒ –
    ‘–Š‡”‘„—•–‡••‘ˆ–Š‡‡ˆˆ‹ ƒ ›”‡•—Ž–‘„•‡”˜‡†‹–Š‡ •–—†›Ǥ

    ͶͶ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 34. Primary Analysis for the Investigator-Assessed PFS for the gCEAS (observed) and
    gCEAS (observed and imputed)
     Comparison between treatments
    Number (%) of 95% Confidence
    Population Treatment N patients with events [a] Hazard Ratio Interval
    ‰ȋ‘„•‡”˜‡†Ȍ    ͳͶ͸ ͺ͵ȋͷ͸ǤͺȌ
    ͲǤͶͳ ͲǤ͵ͳǡͲǤͷͶ
    EGFR  ͳͷͺ ͳ͵ʹȋͺ͵ǤͷȌ
    ‰ȋ‘„•‡”˜‡†ƒ†    ͳ͹͵ ͻ͵ȋͷ͵ǤͺȌ
    ‹’—–‡†Ȍȏ„Ȑ ͲǤͶʹ ͲǤ͵ʹǡͲǤͷͶ
    EGFR  ͳͻʹ ͳͷͶȋͺͲǤʹȌ
    ȏƒȐ‘‰”ƒ‡–Š‘†™‹–Šƒ†Œ—•–‡–‘ˆ–Š‡•–—†›•–”ƒ–‹ˆ‹ ƒ–‹‘ˆƒ –‘”•‹•—•‡†ˆ‘”–Š‡ ‘’ƒ”‹•‘„‡–™‡‡–”‡ƒ–‡–•Ǥ
    ȏ„Ȑ ‘”‡ƒ Š‹’—–ƒ–‹‘ǡ–Š‡ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†—•‹‰ƒŽ‘‰”ƒ–‡•–•–”ƒ–‹ˆ‹‡†„›—–ƒ–‹‘•–ƒ–—•ƒ†”ƒ ‡ǤŠ‡
    ƒ˜‡”ƒ‰‡ ™‹–ŠͻͷΨ ˆ”‘ͳǡͲͲͲ‹’—–ƒ–‹‘•‹•’”‡•‡–‡†Ǥ

      ’—–ƒ–‹‘ƒŽ›•‹•–‘˜ƒŽ—ƒ–‡–Š‡ˆˆ‡ –‘ˆ„•‡”˜‡† —ƒ”†ƒ–͵͸ͲšǦ‹• ‘”†ƒ ‡


    ‹’—–ƒ–‹‘ƒƒŽ›•‹•‘†‡Ž‹‰–Š‡’‘–‡–‹ƒŽ‡ˆˆ‡ –‘ˆ —ƒ”†ƒ–͵͸ͲšǦ —ƒ”†ƒ–͵͸Ͳ
    †‹• ‘”†ƒ ‡‘–Š‡  ‘„•‡”˜‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•™ƒ• ‘†— –‡†ǤŠ‡
    •‡•‹–‹˜‹–›ƒƒŽ›•‹•„›‹’—–ƒ–‹‘ƒƒŽ›•‹•‘†‡ŽŽ‹‰™ƒ•’‡”ˆ‘”‡†„ƒ•‡†‘–Š‡ƒ†
    ƒ ‘—–‹‰ˆ‘” „‡–™‡‡–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ† —ƒ”†ƒ–͵͸ͲǤŠ‡’‘–‡–‹ƒŽ‡ˆˆ‡ –‘ˆ
    —ƒ”†ƒ–͵͸ͲšǦ —ƒ”†ƒ–͵͸Ͳ†‹• ‘”†ƒ ‡‘–Š‡  ™ƒ• ƒŽ —Žƒ–‡†„›–Š‡‘‰”ƒ
    ‘†‡ŽǤŠ‡‹†‡–‹–›„‡–™‡‡–Š‡‘„•‡”˜‡†‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡†  ‘ˆͲǤͶͳȋͻͷΨ ͲǤ͵ͳǡ
    ͲǤͷͶȌƒ†–Š‡‹’—–ƒ–‹‘”‡•—Ž–•ȋͲǤͶʹǡͻͷΨ ‘ˆ‹†‡ ‡ͲǤ͵ʹǡͲǤͷͶȌ†‡‘•–”ƒ–‡•–Šƒ––Š‡Ž‡˜‡Ž‘ˆ
    ‘„•‡”˜‡† —ƒ”†ƒ–͵͸ͲšǦ†‹• ‘”†ƒ ‡†‘‡•‘–‹’ƒ ––Š‡‘„•‡”˜‡†”‡•—Ž–•ǤŠ‡•‡”‡•—Ž–•
    •—’’‘”––Š‡ ‘„‹ƒ–‹‘‘ˆ†ƒ–ƒ†‡”‹˜‡†ˆ”‘ —ƒ”†ƒ–͵͸Ͳƒ† —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡
    ’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•Ǥ
    ‡•‹–‹˜‹–›ƒƒŽ›•‹•ˆ‘”–Š‡‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡† ‹–Š‡ —ƒ”†ƒ–͵͸Ͳ’‘•‹–‹˜‡’‘’—Žƒ–‹‘
    •‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†„›ƒ••—‹‰ƒ”ƒ‰‡‘ˆ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ‹‡•‹–Š‡ —ƒ”†ƒ–͵͸ͲǦ
    ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’‘’—Žƒ–‹‘ȋi.e.ƒ••—‡† ˆ‘”–‹••—‡Ǧǡ ͵͸ͲΪȌǡƒ†–Š‡ƒƒŽ›•‹•”‡•—Ž–•
    ƒ”‡’”‡•‡–‡†‹Table 35ǤŠ‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•”‡•—Ž–••—’’‘”––Š‡’”‹ƒ”›ƒƒŽ›•‹•”‡•—Ž–•ǡ
    ™‹–Š ‘•‹•–‡– Ž‹‹ ƒŽ„‡‡ˆ‹–ǡ†—‡–‘–Š‡Š‹‰Š‘ˆ —ƒ”†ƒ–͵͸Ͳ”‡Žƒ–‹˜‡–‘–‹••—‡–‡•–•ǤŠ‡
     ƒŽ —Žƒ–‹‘•Š‘™‹Table 35ˆ‘”’ƒ–‹‡–•• ”‡‡‡†‹ —•‡†ƒ’”‡˜ƒŽ‡ ‡‘ˆ͸͹ΨǤ

    Table 35. Sensitivity Analysis for Investigator-Assessed PFS (Guardant360 positive


    irrespective of tissue result)
    Estimated
    P(Tissue+|Guardant360+) with 95% CI Estimated HR (Guardant360+) with 95% CI
    Assumed HR
    (Tissue- and Estimated
     PPV Point Estimate 95% CI Guardant360+) HR 95% CI
    ‰ ͲǤͻͻ ͲǤͻ͹ǡͳǤͲͲ ͲǤͶͳ ͲǤͶͳ ͲǤ͵ͳǡͲǤͷͶ
    ȋ‘„•‡”˜‡†Ȍ
       ͲǤͷͲ ͲǤͶͳ ͲǤ͵ͳǡͲǤͷͶ
       ͲǤ͹ͷ ͲǤͶͳ ͲǤ͵ͳǡͲǤͷͶ
       ͳǤͲͲ ͲǤͶͳ ͲǤ͵ͳǡͲǤͷͶ

    Ͷͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Estimated
    P(Tissue+|Guardant360+) with 95% CI Estimated HR (Guardant360+) with 95% CI
    Assumed HR
    (Tissue- and Estimated
     PPV Point Estimate 95% CI Guardant360+) HR 95% CI
    ‰ȋ‘„•‡”˜‡† ͲǤͻͻ ͲǤͻ͹ǡͳǤͲͲ ͲǤͶʹ ͲǤͶʹ ͲǤ͵ʹǡͲǤͷͶ
    ƒ†‹’—–‡†Ȍ
       ͲǤͷͲ ͲǤͶʹ ͲǤ͵ʹǡͲǤͷͶ
       ͲǤ͹ͷ ͲǤͶʹ ͲǤ͵ʹǡͲǤͷͶ
       ͳǤͲͲ ͲǤͶʹ ͲǤ͵ʹǡͲǤͷͷ
    ‘‰”ƒ‡–Š‘†™‹–Šƒ†Œ—•–‡–‘ˆ–Š‡•–—†›•–”ƒ–‹ˆ‹ ƒ–‹‘ˆƒ –‘”•‹•—•‡†–‘‡•–‹ƒ–‡ ™‹–ŠͻͷΨ ˆ‘”–Š‡’ƒ–‹‡–•‹
    –Š‡‰ȋ‘„•‡”˜‡†Ȍƒ†‰ȋ‘„•‡”˜‡†ƒ†‹’—–‡†ȌǤ
    —”–Š‡”ǡ„‡ ƒ—•‡–Š‡†‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•• ”‡‡‡†ˆ‘”–Š‡
    ƒ†‡”‘ŽŽ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†‹‡•™‡”‡‘–™‡ŽŽǦ„ƒŽƒ ‡†ˆ‘””ƒ ‡ƒ†•‘‹‰
    •–ƒ–—•ǡƒƒ††‹–‹‘ƒŽƒƒŽ›•‹•™ƒ• ‘†— –‡†–‘†‡–‡”‹‡–Š‡‹‹—–Šƒ–™‹ŽŽŽ‡ƒ†–‘ƒ
    —‹–›ȋͳǤͲȌŠƒœƒ”†”ƒ–‹‘ƒ––Š‡–™‘Ǧ•‹†‡†ͻͷΨ—’’‡” ‘ˆ‹†‡ ‡„‘—†ˆ‘” —ƒ”†ƒ–͵͸Ͳ’‘•‹–‹˜‡
    ’‘’—Žƒ–‹‘Ǥ••—‹‰ˆ‹š‡†’”‡˜ƒŽ‡ ‡‘ˆ–Š‡EGFRƒ”‡”ƒ†‘„•‡”˜‡†ˆ”‘–Š‡ 
    •ƒ’Ž‡•ǡ–Š‡ ‘””‡•’‘†‹‰–‘–Š‹•–‹’’‹‰’‘‹–™ƒ•†‡–‡”‹‡†–‘Š‡Ž’–‘ƒ††”‡••–Š‡
    ”‘„—•–‡••‘ˆ–Š‡•–—†›”‡•—Ž–•ǤŠ‹•ƒƒŽ›•‹•†‡‘•–”ƒ–‡†–Šƒ–˜ƒŽ—‡ ‘””‡•’‘†‹‰–‘–Š‡
    –‹’’‹‰’‘‹–ƒ••‘ ‹ƒ–‡†™‹–Šƒ —’’‡”Ž‹‹–‘ˆ–Š‡ͻͷΨ αͳǤͲ™ƒ••‹‰‹ˆ‹ ƒ–Ž›Ž‡••–Šƒ
    –Š‡‘„•‡”˜‡†‘ˆͻͺǤ͹Ψȋ‹Table 36„‡Ž‘™Ȍ•—’’‘”–‹‰–Š‡”‘„—•–‡••‘ˆ–Š‡•–—†›”‡•—Ž–•Ǥ
    ‹‹‹Ǥ ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳƒ†–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–•‹‰‹••—‡
    ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳǡi.e.ǡ —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•”‡•—Ž–•
    ‘„‹‡†ǡƒ†–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–—•‹‰–‹••—‡ˆ‘”ƒŽŽƒ– Š‡†’Žƒ•ƒǦ–‹••—‡ˆ”‘–Š‡
    •–—†›‹••Š‘™‹Table 36Ǥ

    Table 36. Concordance between Guardant360 and the cobas ® EGFR Mutation Test Using Tissue
    in Samples from the FLAURA Clinical Study
    EGFR Exon 19 Deletions cobas® EGFR Mutation Test Using Tissue
    Positive Negative Failed Total
    Guardant360
     ‘•‹–‹˜‡ ͳͺͷ ͳ ʹ ͳͺͺ
     ‡‰ƒ–‹˜‡ ͷ͵ ͳͶͳ ͵ ͳͻ͹
     ƒ‹Ž‡† ͳͶ ͳʹ ͳ ʹ͹
     ‘–ƒŽ ʹͷʹ ͳͷͶ ͸ Ͷͳʹ
    ȋͻͷΨ ȌȏƒȐ ͹͹Ǥ͹Ψȏ͹ͳǤͻΨǡͺʹǤͻΨȐ
    ȋͻͷΨ ȌȏƒȐ ͻͻǤ͵Ψȏͻ͸ǤͳΨǡͳͲͲǤͲΨȐ
    EGFR L858R Mutations cobas® EGFR Mutation Test Using Tissue
    Positive Negative Failed Total
    Guardant360
     ‘•‹–‹˜‡ ͻ͸ ʹ ʹ ͳͲͲ
     ‡‰ƒ–‹˜‡ ͶͲ ʹͶʹ ͵ ʹͺͷ
     ƒ‹Ž‡† ͳʹ ͳͶ ͳ ʹ͹
     ‘–ƒŽ ͳͶͺ ʹͷͺ ͸ Ͷͳʹ
    ȋͻͷΨ ȏƒȐ  ͹ͲǤ͸Ψȏ͸ʹǤʹΨǡ͹ͺǤͳΨȐ
    ȋͻͷΨ ȌȏƒȐ ͻͻǤʹΨȏͻ͹ǤͳΨǡͻͻǤͻΨȐ

    Ͷ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    EGFR Exon 19 Deletions or
    L858R Mutations cobas® EGFR Mutation Test Using Tissue
    Positive Negative Failed Total
    Guardant360
     ‘•‹–‹˜‡ ʹͺͳ ʹ Ͷ ʹͺ͹
     ‡‰ƒ–‹˜‡ ͻ͵ Ͷ ͳ ͻͺ
     ƒ‹Ž‡† ʹ͸ Ͳ ͳ ʹ͹
     ‘–ƒŽ ͶͲͲ ͸ ͸ Ͷͳʹ
    ȋͻͷΨ ȌȏƒȐ ͹ͷǤͳΨȏ͹ͲǤͶΨǡ͹ͻǤͶΨȐ
    ȋͻͷΨ ȌȏƒȐ 
    ȏƒȐƒ†™‹–ŠͻͷΨ •ƒ”‡ ƒŽ —Žƒ–‡†„ƒ•‡†‘˜ƒŽ‹†–‡•–”‡•—Ž–•ȋ’‘•‹–‹˜‡‘”‡‰ƒ–‹˜‡ȌǤŠ‡ͻͷΨ‡šƒ –ȋŽ‘’’‡”Ǧ
    ‡ƒ”•‘Ȍ ‹• ƒŽ —Žƒ–‡†Ǥᐑ– ƒŽ —Žƒ–‡†
    ‘ ‘”†ƒ ‡”‡Žƒ–‹˜‡–‘ —ƒ”†ƒ–͵͸ͲšƒŽ‘‡‹••‹‹Žƒ”–‘–Š‡ ‘ ‘”†ƒ ‡‘„–ƒ‹‡†™‹–Š–Š‡
    —ƒ”†ƒ–͵͸Ͳ ‘„‹‡††ƒ–ƒi.e.ǡ —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•”‡•—Ž–• ‘„‹‡†ǤŠ‡
    ’‘‹–‡•–‹ƒ–‡•‘ˆƒ†ƒ† ‘””‡•’‘†‹‰ͻͷΨ •ˆ‘”EGFRš‘ͳͻ‡Ž‡–‹‘•ƒ”‡
    ͹͵ǤͺΨȋ͸ͷǤ͹ΨǡͺͲǤͺΨȌƒ†ͳͲͲΨȋͻͷΨǡͳͲͲΨȌ”‡•’‡ –‹˜‡Ž›ǤŠ‡’‘‹–‡•–‹ƒ–‡•‘ˆƒ†
    ƒ† ‘””‡•’‘†‹‰ͻͷΨ •ˆ‘”EGFRͺͷͺ—–ƒ–‹‘•ƒ”‡͸ͺǤ͸Ψȋͷ͸ǤͶΨǡ͹ͻǤͳΨȌƒ†ͻͺǤ͸Ψ
    ȋͻͷǤͲΨǡͻͻǤͺΨȌ”‡•’‡ –‹˜‡Ž›ǤŠ‡ˆ‘”EGFRš‘ͳͻ‡Ž‡–‹‘•‘”ͺͷͺ™ƒ•͹ʹǤͲΨ™‹–Šƒ
    ‘””‡•’‘†‹‰ͻͷΨ ‘ˆ͸ͷǤͷΨǡ͹ͺǤͲΨǤ
    •‘’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘ ’ƒ–‹‡–•‡‰ƒ–‹˜‡ˆ‘”EGFR—–ƒ–‹‘•ȋš‘ͳͻ‡Ž‡–‹‘•‘”
    ͺͷͺȌ„›–‹••—‡–‡•–‹‰™‡”‡ƒ˜ƒ‹Žƒ„Ž‡ǡ ‘—Ž†‘–„‡ ƒŽ —Žƒ–‡†—•‹‰•ƒ’Ž‡•ˆ”‘ Ǥ
    Š‡ˆ‘”EGFRš‘ͳͻ‡Ž‡–‹‘•‘”ͺͷͺ”‡Žƒ–‹˜‡–‘–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–—•‹‰
    –‹••—‡™ƒ• ƒŽ —Žƒ–‡†—•‹‰•ƒ’Ž‡•ˆ”‘–Š‡  Ž‹‹ ƒŽ•–—†›•Š‘™‹Table 37Ǥˆ‘–‡ǡ–Š‡
    •‹‰Ž‡•ƒ’Ž‡–Šƒ––‡•–‡†’‘•‹–‹˜‡ˆ‘”„› —ƒ”†ƒ–͵͸Ͳš„—–‡‰ƒ–‹˜‡„›–Š‡ ‘„ƒ• ̺EGFR
    —–ƒ–‹‘‡•–—•‹‰–‹••—‡ ‘’”‹•‡†ƒ— ‘‘EGFR‡š‘ͳͻ†‡Ž‡–‹‘ǡ’Ǥ͹ͷͳ̴ ͹ͷͻ†‡Ž‹•ǡ
    ™Š‹ Š‹•‘––ƒ”‰‡–‡†„›–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–Ǥ

    Table 37. Concordance between Guardant360 and the cobas ® EGFR Mutation Test Using Tissue
    in Samples from the NILE Clinical Study
    EGFR Exon 19 Deletions or
    L858R Mutations cobas® EGFR Mutation Test Using Tissue
    Positive Negative Failed Total
    Guardant360    
    ‘•‹–‹˜‡ ͳͶ ͳ Ͳ ͳͷ
    ‡‰ƒ–‹˜‡ Ͳ ͹͵ ʹ ͹ͷ
    ƒ‹Ž‡† Ͳ ʹ Ͳ ʹ
    ‘–ƒŽ ͳͶ ͹͸ ʹ ͻʹ
    ȋͻͷΨ ȌȏƒȐ ͳͲͲΨȏ͹͸ǤͺΨǡͳͲͲǤͲΨȐ
    ȋͻͷΨ ȌȏƒȐ ͻͺǤ͹ΨȏͻʹǤ͹ΨǡͳͲͲǤͲΨȐ
    ȏƒȐƒ†™‹–ŠͻͷΨ •ƒ”‡ ƒŽ —Žƒ–‡†„ƒ•‡†‘˜ƒŽ‹†–‡•–”‡•—Ž–•ȋ’‘•‹–‹˜‡‘”‡‰ƒ–‹˜‡ȌǤŠ‡ͻͷΨ‡šƒ –ȋŽ‘’’‡”Ǧ
    ‡ƒ”•‘Ȍ ‹• ƒŽ —Žƒ–‡†Ǥ

    ͹ǤʹǤ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”EGFR͹ͻͲ—–ƒ–‹‘•


    ͵Ž‹‹ ƒŽ–—†›‡•‹‰
    ͵™ƒ•ƒŠƒ•‡ ǡ—Ž–‹ ‡–‡”‹–‡”ƒ–‹‘ƒŽǡ‘’‡ǦŽƒ„‡Žǡ”ƒ†‘‹œ‡†•–—†›–‘ƒ••‡••–Š‡‡ˆˆ‹ ƒ ›
    ƒ†•ƒˆ‡–›‘ˆ  ˜‡”•—•’Žƒ–‹—Ǧ„ƒ•‡††‘—„Ž‡– Š‡‘–Š‡”ƒ’›ƒ••‡ ‘†ǦŽ‹‡–Š‡”ƒ’›‹
    ’ƒ–‹‡–•™‹–ŠŽ‘ ƒŽŽ›ƒ†˜ƒ ‡†‘”‡–ƒ•–ƒ–‹ EGFR͹ͻͲ—–ƒ–‹‘Ǧ’‘•‹–‹˜‡ǡ™Š‘Šƒ†

    Ͷ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ’”‘‰”‡••‡†ˆ‘ŽŽ‘™‹‰–”‡ƒ–‡–™‹–ŠͳŽ‹‡–”‡ƒ–‡–™‹–Šƒƒ’’”‘˜‡†EGFRǦ ƒ‰‡–Ǥƒ–‹‡–•
    ™‡”‡”ƒ†‘‹œ‡†‹ƒʹǣͳ”ƒ–‹‘–‘  ‘”’‡‡–”‡š‡†’Ž—• ‹•’Žƒ–‹Ȁ ƒ”„‘’Žƒ–‹Ǥ
    ƒ–‹‡–•™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘–Š‡’”‡•‡ ‡‘ˆEGFR͹ͻͲ‹–Š‡‹”–—‘”ƒ•†‡–‡”‹‡†„›–Š‡
    ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–‹ƒ ‡–”ƒŽŽƒ„‘”ƒ–‘”›ǤŠ‹• Ž‹‹ ƒŽ•–—†›™ƒ•—•‡†–‘•—’’‘”––Š‡
    ƒ’’”‘˜ƒŽ‘ˆ  —†‡”ʹͲͺͲ͸ͷ—’’Ž‡‡–͸Ǥ
    —ƒ”†ƒ–͵͸Ͳš͵”‹†‰‹‰–—†›‡•‹‰
    ”‡–”‡ƒ–‡–„Ž‘‘†•ƒ’Ž‡•™‡”‡ ‘ŽŽ‡ –‡†ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘–Š‡͵ Ž‹‹ ƒŽ•–—†›
    ™‡”‡—•‡†–‘ƒ••‡••–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•ˆ‘”
      –Š‡”ƒ’›™‹–ŠEGFR͹ͻͲ—–ƒ–‹‘Ǧ’‘•‹–‹˜‡‡–ƒ•–ƒ–‹ ™Š‘•‡†‹•‡ƒ•‡Šƒ•
    ’”‘‰”‡••‡†‘‘”ƒˆ–‡”EGFR –Š‡”ƒ’›Ǥ
    ”‡–”‡ƒ–‡–•ƒ’Ž‡•ˆ”‘ʹͺ͹͵’ƒ–‹‡–•ȋ͸ͺΨ‘ˆ–Š‡”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘Ȍ™‡”‡–‡•–‡†
    ™‹–Š —ƒ”†ƒ–͵͸Ͳ‹–Š‡”‡•‡ƒ” Š•‡––‹‰ƒ•’ƒ”–‘ˆƒ‡š’Ž‘”ƒ–‘”›ƒƒŽ›•‹•ǤŠ‹• —ƒ”†ƒ–͵͸Ͳ
    –‡•–‹‰–‘‘’Žƒ ‡„‡ˆ‘”‡–Š‹•†‹ƒ‰‘•–‹ •–—†›™ƒ•‹‹–‹ƒ–‡†Ǥ
    ŽŽ’ƒ–‹‡–•ƒ’Ž‡•™‘—Ž†‹†‡ƒŽŽ›Šƒ˜‡„‡‡–‡•–‡†—•‹‰ —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‹•†‹ƒ‰‘•–‹ •–—†›ǯ•
    ‡ˆˆ‹ ƒ ›ƒƒŽ›•‹•Ǥ ‘™‡˜‡”ǡ’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•™‡”‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”‘Ž›ʹ͸ͷ’ƒ–‹‡–•ȋ͸͵Ψ
    ‘ˆ–Š‡”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘ȌǤ••— Šǡ–Š‹••ƒ’Ž‡•‡–™ƒ••—’’Ž‡‡–‡†„›͵ͷ’ƒ–‹‡–•ˆ‘”™Š‘
    †ƒ–ƒ™ƒ•’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†‘ —ƒ”†ƒ–͵͸Ͳ„—–ˆ‘”™Š‘‘’Žƒ•ƒ”‡ƒ‹•ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”
    –‡•–‹‰™‹–Š —ƒ”†ƒ–͵͸ͲšǤŠ‡ƒƒŽ›–‹ ƒŽ ‘ ‘”†ƒ ‡•–—†›†‡• ”‹„‡†ƒ„‘˜‡ǡ•—’’Ž‡‡–‡†„›
    †‡‘•–”ƒ–‹‘‘ˆ–Š‡ ‘’ƒ”ƒ„‹Ž‹–›‘ˆ‡›’‡”ˆ‘”ƒ ‡ Šƒ”ƒ –‡”‹•–‹ •ǡi.e.ǡ‘ƒ†’”‡ ‹•‹‘•
    „‡–™‡‡–Š‡ —ƒ”†ƒ–͵͸Ͳšƒ†ǡ™ƒ•’‡”ˆ‘”‡†–‘•—’’‘”––Š‡˜ƒŽ‹†‹–›‘ˆ ‘„‹‹‰†ƒ–ƒ
    ‰‡‡”ƒ–‡†‘ —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•ˆ‘”–Š‡†‡–‡ –‹‘‘ˆEGFR͹ͻͲ—–ƒ–‹‘
    ‡ˆ‡”–‘ Section 6.12 Concordance - Guardant360 CDx Comparison to Guardant360 LDT Ǥ
    —”–Š‡”ƒ„Ž‘‘† ‘ŽŽ‡ –‹‘ ‘ ‘”†ƒ ‡•–—†›‡•–ƒ„Ž‹•Š‹‰–Š‡ ‘ ‘”†ƒ ‡„‡–™‡‡•ƒ’Ž‡•
    ‘ŽŽ‡ –‡†‹–”‡ ‡ŽŽǦ ”‡‡•ƒ†–Š‡Ǧ™ƒ• ‘†— –‡†–‘•—’’‘”––Š‡˜ƒŽ‹†‹–›‘ˆ–Š‡
    †ƒ–ƒ‰‡‡”ƒ–‡†„›–‡•–‹‰•ƒ’Ž‡• ‘ŽŽ‡ –‡†‹Ǧȋ‡ˆ‡”–‘Section 6.13.a Blood Collection
    Tube Concordance Ǥ
    a. Bridging Study Inclusion and Exclusion Criteria
    x Inclusion Criteria for plasma samples from the AURA3 clinical study
    o ƒ–‹‡–• ”‡‡‡†ˆ‘”–Š‡͵ Ž‹‹ ƒŽ•–—†›™‹–Š†‘ —‡–‡†‹ˆ‘”‡† ‘•‡–ˆ‘”„Ž‘‘†
    •ƒ’Ž‡—•‡ˆ‘”†‹ƒ‰‘•–‹ †‡˜‡Ž‘’‡–
    o ”‡Ǧ–”‡ƒ–‡––‹‡’‘‹–’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–‡•–‹‰—•‹‰ —ƒ”†ƒ–͵͸Ͳ
    x Exclusion Criteria for plasma samples from the AURA3 clinical study
    o „•‡ ‡‘ˆ’Žƒ•ƒˆ‘”–‡•–‹‰‘ —ƒ”†ƒ–͵͸Ͳ
    o ˆ‘”‡† ‘•‡–™‹–Š†”ƒ™
    o Š‹ƒƒ‹Žƒ†’ƒ–‹‡–•
    b. Follow-up Schedule
    Š‡ —ƒ”†ƒ–͵͸ͲšEGFR͹ͻͲ„”‹†‰‹‰•–—†›‹˜‘Ž˜‡†‘Ž›”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ’Žƒ•ƒ
    •ƒ’Ž‡•Ǣƒ••— Šǡƒ††‹–‹‘ƒŽ’ƒ–‹‡–ˆ‘ŽŽ‘™Ǧ—’™ƒ• ‘†— –‡†Ǥ
    c. Clinical Endpoints
    Š‡ Ž‹‹ ƒŽ‡†’‘‹–—•‡†–‘ƒ••‡••  ‡ˆˆ‹ ƒ ›‹–Š‡͵ Ž‹‹ ƒŽ•–—†›’”‹ƒ”›‘„Œ‡ –‹˜‡
    ™ƒ•‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡† ǡ™Š‹ Š™ƒ•†‡ˆ‹‡†ƒ•–Š‡–‹‡‹–‡”˜ƒŽ„‡–™‡‡”ƒ†‘‹œƒ–‹‘ƒ†

    Ͷͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    –Š‡ˆ‹”•– ’”‘‰”‡••‹‘‘”‘”–ƒŽ‹–›‡˜‡–ǤŠ‡ —ƒ”†ƒ–͵͸ͲšEGFR͹ͻͲ„”‹†‰‹‰•–—†›
    —•‡•–Š‡•ƒ‡ Ž‹‹ ƒŽ‡†’‘‹–ˆ‘”‹–•’”‹ƒ”›‘„Œ‡ –‹˜‡Ǥ
    x Diagnostic Objective and Endpoint
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡‘ˆ–Š‡•–—†›™ƒ•–‘†‡‘•–”ƒ–‡–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ
    —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™Š‘Šƒ˜‡’”‘‰”‡••‡†‘‘”ƒˆ–‡”EGFR 
    –Š‡”ƒ’›™‹–ŠEGFR͹ͻͲ—–ƒ–‹‘•ˆ‘”–”‡ƒ–‡–™‹–Š  ǤŠ‹•‘„Œ‡ –‹˜‡™ƒ•ƒ••‡••‡†
    „› ‘’ƒ”‹‰–Š‡‡ˆˆ‹ ƒ ›ƒ•†‡–‡”‹‡†„› –‘ ˜ͳǤͳ„›‹˜‡•–‹‰ƒ–‘”ƒ••‡••‡–‘ˆ
    •‹‰Ž‡Ǧƒ‰‡–   ‘’ƒ”‡†™‹–Š Š‡‘–Š‡”ƒ’›‹–Š‡–‹••—‡Ǧ’‘•‹–‹˜‡ǡ —ƒ”†ƒ–͵͸ͲšǦ
    ’‘•‹–‹˜‡’ƒ–‹‡–•‡”‘ŽŽ‡†‹͵Ǥ
    Š‡’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆ–‹••—‡Ǧ‡‰ƒ–‹˜‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡’ƒ–‹‡–•‹–Š‡‡ˆˆ‡ –‹˜‡‡••
    ‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš™ƒ•ƒ••‡••‡†–Š”‘—‰Š•‡•‹–‹˜‹–›ƒƒŽ›•‹•„ƒ•‡†‘”ƒ†‘Ž›•‡Ž‡ –‡†
    –‹••—‡Ǧ‡‰ƒ–‹˜‡͵• ”‡‡Ǧˆƒ‹Ž—”‡•ƒ’Ž‡•Ǥ
     ‘—–ƒ„‹Ž‹–›‘ˆ‘Š‘”–
    Š‡͵†‹ƒ‰‘•–‹ •–—†›‹ Ž—†‡†͵ͲͲ‘ˆ–Š‡–‘–ƒŽͶͳͻȋ͹ͳǤ͸ΨȌ’ƒ–‹‡–•”ƒ†‘‹œ‡†‹–Š‡͵
    Ž‹‹ ƒŽ•–—†›ȋFigure 4ȌǤˆ–Š‡•‡ǡͳͻͳ’ƒ–‹‡–•ȋͶͷǤ͸Ψ‘ˆ–Š‡–‘–ƒŽ’‘’—Žƒ–‹‘Ȍ–‡•–‡†’‘•‹–‹˜‡„›
    —ƒ”†ƒ–͵͸Ͳƒ†™‡”‡‹ Ž—†‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹••‡–ǡͻ͵ȋ͵ͳǤͲΨȌ–‡•–‡†‡‰ƒ–‹˜‡ǡƒ†
    ͳ͸ȋͷǤ͵ΨȌˆƒ‹Ž‡†–‡•–‹‰ǤŠ‡ƒƒŽ›•‹••‡–• ‘’”‹•‡†‹ƒ‰‘•–‹ †ƒ–ƒ‰‡‡”ƒ–‡†—•‹‰ —ƒ”†ƒ–͵͸Ͳš
    ȋʹ͸ͷȀ͵ͲͲǡͺͺǤ͵ΨȌ•—’’Ž‡‡–‡†„›†ƒ–ƒ’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†‘ —ƒ”†ƒ–͵͸Ͳȋ͵ͷȀ͵ͲͲǡͳͳǤ͹ΨȌ
    ƒ•†‡• ”‹„‡†ƒ„‘˜‡Ǥ ‡”‡ƒˆ–‡”ǡ —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•”‡•—Ž–• ‘„‹‡†ƒ”‡”‡ˆ‡””‡†
    –‘ƒ• —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•Ǥ
    •͵”ƒ†‘‹œ‡†’ƒ–‹‡–• ‘’”‹•‡†‘Ž›–Š‘•‡’‘•‹–‹˜‡„›–‹••—‡–‡•–‹‰ˆ‘”EGFR͹ͻͲ
    —–ƒ–‹‘•ǡƒ•‡•‹–‹˜‹–›ƒƒŽ›•‹•–‘ƒ••‡••–Š‡’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆ–‹••—‡Ǧ‡‰ƒ–‹˜‡ǡ —ƒ”†ƒ–͵͸Ͳ
    ’Žƒ•ƒǦ’‘•‹–‹˜‡’ƒ–‹‡–•™ƒ•ƒŽ•‘’‡”ˆ‘”‡†—•‹‰ͳͷͲ”ƒ†‘Ž›•‡Ž‡ –‡†•ƒ’Ž‡•†‡”‹˜‡†ˆ”‘–Š‡
    • ”‡‡‡†’‘’—Žƒ–‹‘‘ˆ͵–Šƒ–ˆƒ‹Ž‡†• ”‡‡‹‰†—‡–‘ƒ‡‰ƒ–‹˜‡EGFR͹ͻͲ–‹••—‡–‡•–”‡•—Ž–
    ȋͳͷͲȀ͵Ͷ͵ǡͶ͵Ǥ͹ΨȌǤ
    –—†›‘’—Žƒ–‹‘‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡ƒ”ƒ‡–‡”•
    ‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•‡”‘ŽŽ‡†‹–Š‡͵ Ž‹‹ ƒŽ•–—†›
    ȋ Ȍ™‡”‡ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡–‘–Š‡ —ƒ”†ƒ–͵͸ͲšEGFR͹ͻͲ„”‹†‰‹‰•–—†›’‘’—Žƒ–‹‘•ƒ•
    †‡ˆ‹‡†„› —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•ȋ‰Ȍƒ†ƒ••‡••‡†ˆ‘”–”‡ƒ–‡–ƒ”„ƒŽƒ ‡Ǥ••Š‘™‹Table
    38ǡ†‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‹–Š‡ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›ƒƒŽ›•‹••—„‰”‘—’•™‡”‡
    ™‡ŽŽǦ„ƒŽƒ ‡†„‡–™‡‡–”‡ƒ–‡–ƒ”•ǡƒ‹–ƒ‹‹‰ƒ’’”‘š‹ƒ–‡Ž›ƒʹǣͳ”ƒ†‘‹œƒ–‹‘™‹–Š‹‡ƒ Š
    ‰”‘—’Ǥ

    Ͷͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    
    Figure 4. Guardant360 CDx EGFR T790M Bridging Study Patient Accountability and Analysis
    Set Definitions

    Table 38. Baseline Demographics and Clinical Characteristics


    gCEAS FAS
    TAGRISSO Chemotherapy TAGRISSO Chemotherapy
    Characteristic (n=138) (n=53) (n=279) (n=140)
    ‰‡ȋ›‡ƒ”•Ȍ ‡†‹ƒȋ”ƒ‰‡Ȍ ͸ͳǤͲȋ͵ͶǡͺʹȌ ͸͵ǤͲȋʹͲǡͺͲȌ ͸ʹǤͲȋʹͷǡͺͷȌ ͸͵ǤͲȋʹͲǡͻͲȌ
    ‰‡‰”‘—’ δ͸ͷ ͺ͸ȋ͸ʹǤ͵Ȍ ʹͺȋͷʹǤͺȌ ͳ͸ͷȋͷͻǤͳȌ ͹͹ȋͷͷǤͲȌ
    ȋ›‡ƒ”•ȌǡȋΨȌ η͸ͷ ͷʹȋ͵͹Ǥ͹Ȍ ʹͷȋͶ͹ǤʹȌ ͳͳͶȋͶͲǤͻȌ ͸͵ȋͶͷǤͲȌ
    ‡šǡȋΨȌ ƒŽ‡ ͷͲȋ͵͸ǤʹȌ ͳ͵ȋʹͶǤͷȌ ͳͲ͹ȋ͵ͺǤͶȌ Ͷ͵ȋ͵ͲǤ͹Ȍ
    ‡ƒŽ‡ ͺͺȋ͸͵ǤͺȌ ͶͲȋ͹ͷǤͷȌ ͳ͹ʹȋ͸ͳǤ͸Ȍ ͻ͹ȋ͸ͻǤ͵Ȍ
    ƒ ‡ǡȋΨȌ •‹ƒ ͹Ͷȋͷ͵Ǥ͸Ȍ ͵ͷȋ͸͸ǤͲȌ ͳͺʹȋ͸ͷǤʹȌ ͻʹȋ͸ͷǤ͹Ȍ
    ‘‹‰ ‡˜‡” ͻͷȋ͸ͺǤͺȌ ͵ͻȋ͹͵Ǥ͸Ȍ ͳͺͻȋ͸͹Ǥ͹Ȍ ͻͶȋ͸͹ǤͳȌ
    •–ƒ–—•ǡȋΨȌ —””‡– ͷȋ͵Ǥ͸Ȍ ͳȋͳǤͻȌ ͳͶȋͷǤͲȌ ͺȋͷǤ͹Ȍ
    ‘”‡” ͵ͺȋʹ͹ǤͷȌ ͳ͵ȋʹͶǤͷȌ ͹͸ȋʹ͹ǤʹʹȌ ͵ͺȋʹ͹ǤͳȌ
     •–ƒ‰‹‰ Ǧ  ʹͲȋͳͶǤͷȌ ͳͲȋͳͺǤͻȌ ͷʹȋͳͺǤ͸Ȍ ͵ͳȋʹʹǤͳȌ
    ƒ–†‹ƒ‰‘•‹•  ͳͳ͹ȋͺͶǤͺȌ Ͷ͵ȋͺͳǤͳȌ ʹʹͷȋͺͲǤ͸Ȍ ͳͲͻȋ͹͹ǤͻȌ
    ‹••‹‰ ͳȋͲǤ͹Ȍ Ͳ ʹȋͲǤ͹Ȍ Ͳ
    ˜‡”ƒŽŽ ‡–ƒ•–ƒ–‹  ͳ͵Ͷȋͻ͹ǤͳȌ ͷ͵ȋͳͲͲǤͲȌ ʹ͸͸ȋͻͷǤ͵Ȍ ͳ͵ͺȋͻͺǤ͸Ȍ
    †‹•‡ƒ•‡ ‘ ƒŽŽ›ƒ†˜ƒ ‡† ͶȋʹǤͻȌ Ͳ ͳ͵ȋͶǤ͹Ȍ ʹȋͳǤͶȌ
    Žƒ••‹ˆ‹ ƒ–‹‘
    ‹•–‘Ž‘‰›–›’‡ †‡‘ ƒ” ‹‘ƒ ͳ͵͹ȋͻͻǤ͵Ȍ ͷ͵ȋͳͲͲǤͲȌ ʹ͹͹ȋͻͻǤ͵Ȍ ͳͶͲȋͳͲͲȌ
    –Š‡” ͳȋͲǤ͹Ȍ Ͳ ʹȋͲǤ͹Ȍ Ͳ

    Ž•‘ǡ‘ˆ‹–‡”‡•–‹–Š‹•ƒƒŽ›•‹•‹•–Š‡ ‘’ƒ”‹•‘„‡–™‡‡͵’ƒ–‹‡–•™‹–Š’Žƒ•ƒƒ˜ƒ‹Žƒ„Ž‡ˆ‘”
    –‡•–‹‰‹–Š‹•†‹ƒ‰‘•–‹ •–—†›ȋ‰Ȍƒ†–Š‘•‡™‹–Š‘—–ȋ‰Ȍ–‘‡˜ƒŽ—ƒ–‡ ‘’ƒ”ƒ„‹Ž‹–›ȋ Table 39 Ǥ

    ͷͲ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •™‡”‡™‡ŽŽǦ„ƒŽƒ ‡†„‡–™‡‡–”‡ƒ–‡–ƒ”•ˆ‘”
    „‘–Š–Š‡‰ƒ†‰™‹–Š–Š‡‡š ‡’–‹‘‘ˆ•‹ƒ”ƒ ‡ȋͺͻǤͳΨ‘•‹‡”–‹‹„˜•Ǥ͸ͷǤͷΨ Š‡‘–Š‡”ƒ’›Ȍ
    ƒ†•‡šȋͷ͸Ǥ͵Ψ‘•‹‡”–‹‹„˜•Ǥ͹ͲǤͻΨ Š‡‘–Š‡”ƒ’›Ȍ‹–Š‡‰Ǥ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ
    Šƒ”ƒ –‡”‹•–‹ •„‡–™‡‡‰ƒ†‰™‡”‡ ‘’ƒ”ƒ„Ž‡ǡ™‹–Š–Š‡‡š ‡’–‹‘‘ˆƒ‰‡η͸ͷȋͶͷǤͲΨ‰˜•Ǥ
    ͵ͷǤ͵Ψ‰ǡ’αͲǤͲ͸ͻ͹Ȍǡ•‹ƒ”ƒ ‡ȋ͸ͲǤ͵Ψ‰˜•Ǥ͹ͺǤʹΨ‰ǡ’αͲǤͲͲͲͷȌǡƒ†‡˜‡”•‘‹‰•–ƒ–—•
    ȋ͸ͷǤ͹Ψ‰˜•Ǥ͹ʹǤ͵Ψ‰ǡ’αͲǤͳͻ͵ͳȌǤ

    Table 39. Comparison between AURA3 Patients with Plasma Available for Testing in this
    Diagnostic Study (gAS) and Those Without (gNT)
    gAS gNT
    TAGRISS Chemo- Chemo-
    O therapy Total TAGRISS therapy Total 2-sided p
    Characteristic (n=215) (n=85) (n=300) O (n=64) (n=55) (n=119) value [a]
    ‰‡‰”‘—’ δ͸ͷ ͳʹͳ ͶͶȋͷͳǤͺ  ͳ͸ͷ ͶͶȋ͸ͺǤͺ  ͵͵ȋ͸Ͳ  ͹͹ȋ͸ͶǤ͹ 
    ȋ›‡ƒ”•Ȍǡ ȋͷ͸Ǥ͵Ȍ ȋͷͷǤͲȌ
    ȋΨȌ ͲǤͲ͸ͻ͹
    η͸ͷ ͻͶȋͶ͵Ǥ͹Ȍ ͶͳȋͶͺǤʹȌ ͳ͵ͷ ʹͲȋ͵ͳǤʹȌ ʹʹȋͶͲȌ Ͷʹȋ͵ͷǤ͵Ȍ
    ȋͶͷǤͲȌ
    ‡šǡȋΨȌ ‡ƒŽ‡ ͳ͵͸ ͷͺȋ͸ͺǤʹȌ ͳͻͶ ͵͸ȋͷ͸Ǥ͵Ȍ ͵ͻȋ͹ͲǤͻȌ ͹ͷȋ͸͵ǤͲȌ
    ͲǤ͹ͷʹͲ
    ȋ͸͵Ǥ͵Ȍ ȋ͸ͶǤ͹Ȍ
    ƒ ‡ǡȋΨȌ •‹ƒ ͳʹͷ ͷ͸ȋ͸ͷǤͻ  ͳͺͳ ͷ͹ȋͺͻǤͳȌ ͵͸ȋ͸ͷǤͷȌ ͻ͵ȋ͹ͺǤʹȌ
    ͲǤͲͲͲͷ
    ȋͷͺǤͳȌ ȋ͸ͲǤ͵Ȍ
    ‘‹‰ ‡˜‡” ͳͶͳ ͷ͸ȋ͸ͷǤͻ  ͳͻ͹ Ͷͺȋ͹ͷǤͲȌ ͵ͺȋ͸ͻǤͳȌ ͺ͸ȋ͹ʹǤ͵Ȍ
    •–ƒ–—• ȋ͸ͷǤ͸Ȍ ȋ͸ͷǤ͹Ȍ
    ͲǤͳͻ͵ͳ
    —””‡–Ȁ ͹Ͷȋ͵ͶǤͶȌ ʹͻȋ͵ͶǤͳȌ ͳͲ͵ ͳ͸ȋʹͷǤͲȌ ͳ͹ȋ͵ͲǤͻȌ ͵͵ȋʹ͹Ǥ͹Ȍ
    ‘”‡” ȋ͵ͶǤ͵Ȍ
     •–ƒ‰‡ƒ– Ǧ  ͵ͻȋͳͺǤͳȌ ʹ͵ȋʹ͹ǤͳȌ ͸ʹȋʹͲǤ͹Ȍ ͳ͵ȋʹͲǤ͵Ȍ ͺȋͳͶǤͷȌ ʹͳȋͳ͹Ǥ͸Ȍ
    †‹ƒ‰‘•‹•  ͳ͹Ͷ ͸ʹȋ͹ʹǤͻ  ʹ͵͸ ͷͳȋ͹ͻǤ͹Ȍ Ͷ͹ȋͺͷǤͷȌ ͻͺȋͺʹǤͶȌ
    ͲǤͶ͸ͷ͹
    ȋͺͲǤͻȌ ȋ͹ͺǤ͹Ȍ
    ‹••‹‰ ʹȋͲǤͻȌ ͲȋͲȌ ʹȋͲǤ͹Ȍ ͲȋͲȌ ͲȋͲȌ ͲȋͲȌ
    ˜‡”ƒŽŽ ‡–ƒ•–ƒ–‹  ʹͲͶ ͺͶȋͻͺǤͺ  ʹͺͺ ͸ʹȋͻ͸ǤͻȌ ͷͶȋͻͺǤʹȌ ͳͳ͸
    †‹•‡ƒ•‡ ȋͻͶǤͻȌ ȋͻ͸ǤͲȌ ȋͻ͹ǤͷȌ
    Žƒ••‹ˆ‹ ƒ–‹‘ ‘ ƒŽŽ› ͲǤͷ͹ͳʹ
    ͳͳȋͷǤͳȌ ͳȋͳǤʹȌ ͳʹȋͶǤͲȌ ʹȋ͵ǤͳȌ ͳȋͳǤͺȌ ͵ȋʹǤͷȌ
    ƒ†˜ƒ ‡†
    ‹•–‘Ž‘‰› †‡‘Ǧ ʹͳͶ ͺͷȋͳͲͲȌ ʹͻͻȋͻǤ͹Ȍ ͸ͶȋͳͲͲȌ ͷͷȋͳͲͲȌ ͳͳͻȋͳͲͲȌ
    –›’‡ ƒ” ‹‘ƒ ȋͻͻǤͷȌ ͳǤͲͲͲͲ
    –Š‡” ͳȋͲǤͷȌ Ͳ Ͳ Ȍ ͳȋͲǤ͵Ȍ Ͳ Ͳ Ȍ Ͳ Ͳ Ȍ Ͳ Ͳ Ȍ
    ȏƒȐʹǦ•‹†‡†’Ǧ˜ƒŽ—‡‹•„ƒ•‡†‘Š‹Ǧ•“—ƒ”‡–‡•–ˆ‘”–Š‡ ‘’ƒ”‹•‘•Ǥ–ƒ–‹•–‹ ƒŽ ‘’ƒ”‹•‘‹•„ƒ•‡†‘‘Ǧ‹••‹‰˜ƒŽ—‡•Ǥ

    ƒˆ‡–›ƒ†ˆˆ‡ –‹˜‡‡••‡•—Ž–•
    a. Safety
    ƒ–ƒ”‡‰ƒ”†‹‰–Š‡•ƒˆ‡–›‘ˆ  –Š‡”ƒ’›™‡”‡’”‡•‡–‡†‹–Š‡‘”‹‰‹ƒŽ†”—‰ƒ’’”‘˜ƒŽƒ†ƒ”‡
    •—ƒ”‹œ‡†‹–Š‡†”—‰Žƒ„‡ŽǤ‡ˆ‡”–‘–Š‡  Žƒ„‡Žˆ‘”‘”‡‹ˆ‘”ƒ–‹‘Ǥ‘ƒ†˜‡”•‡‡˜‡–•
    ™‡”‡”‡’‘”–‡†‹–Š‡ ‘†— –‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†‹‡•ƒ•–Š‡•‡‹˜‘Ž˜‡†”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ
    „ƒ‡†•’‡ ‹‡•‘Ž›Ǥ
    b. Effectiveness Results
    ‹Ǥ  ‹ƒ–‹‡–•‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳˆ‘”EGFR͹ͻͲ—–ƒ–‹‘•
    Š‡‡ˆˆ‹ ƒ ›‘ˆ•‹‰Ž‡Ǧƒ‰‡–  ”‡Žƒ–‹˜‡–‘ Š‡‘–Š‡”ƒ’›‹’ƒ–‹‡–•’‘•‹–‹˜‡ˆ‘”EGFR
    ͹ͻͲ—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸Ͳȋ‰Ȍ‹••Š‘™‹Table 40ǤŠ‡‘„•‡”˜‡†  ‘ˆͲǤ͵Ͷ

    ͷͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ȋͻͷΨ ͲǤʹʹǡͲǤͷ͵Ȍ™ƒ••‹‹Žƒ”–‘–Š‡ˆ—ŽŽ͵”ƒ†‘‹œ‡†’‘’—Žƒ–‹‘ȋ ǡ  ͲǤ͵ͲǡͻͷΨ
     ͲǤʹ͵ǡͲǤͶͳȌǤŠ‹•†‡‘•–”ƒ–‡• Ž‹‹ ƒŽŽ›”‡Ž‡˜ƒ–‘•‹‡”–‹‹„‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸Ͳ
    ‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ
    ƒ’ŽƒǦ‡‹‡”ƒƒŽ›•‹•‘ˆ ‹–Š‡‰‹•’”‡•‡–‡†‹Figure 5Ǥ

    Table 40. Investigator-Assessed PFS in the gCEAS and FAS


     Comparison between treatments
    Number (%) of
    patients with events Hazard Ratio
    Population Treatment N [a] (95% CI) 2-sided p-value
    ‰ȏ„Ȑ    ͳ͵ͺ ͺͷȋ͸ͳǤ͸Ȍ
    ͲǤ͵ͶȋͲǤʹʹǡͲǤͷ͵  δͲǤͲͲͲͳ
    Š‡‘–Š‡”ƒ’› ͷ͵ ͶͺȋͻͲǤ͸Ȍ
    ȏ„Ȑ    ʹ͹ͻ ͳͶͲȋͷͲǤʹȌ
    ͲǤ͵ͲȋͲǤʹ͵ǡͲǤͶͳ  δͲǤͲͲͲͳ
    Š‡‘–Š‡”ƒ’› ͳͶͲ ͳͳͲȋ͹ͺǤ͸Ȍ
    ȏƒȐ”‘‰”‡••‹‘‡˜‡–•–Šƒ–†‘‘–‘ —”™‹–Š‹ʹ• Š‡†—Ž‡†˜‹•‹–•ȋ’Ž—•˜‹•‹–™‹†‘™Ȍ‘ˆ–Š‡Žƒ•–‡˜ƒŽ—ƒ„Ž‡ƒ••‡••‡–ȋ‘”
    ”ƒ†‘‹œƒ–‹‘Ȍƒ”‡ ‡•‘”‡†ƒ†–Š‡”‡ˆ‘”‡‡š Ž—†‡†‹–Š‡—„‡”‘ˆ‡˜‡–•Ǥ”‘‰”‡••‹‘‹ Ž—†‡•†‡ƒ–Š•‹–Š‡ƒ„•‡ ‡
    ‘ˆ ȋ˜ͳǤͳȌ’”‘‰”‡••‹‘Ǥ
    ȏ„ȐŠ‡ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†—•‹‰ƒŽ‘‰”ƒ–‡•–•–”ƒ–‹ˆ‹‡†„›”ƒ ‡ǤŠƒœƒ”†”ƒ–‹‘δͳˆƒ˜‘”•  

    
    Figure 5. Kaplan-Meier Plot of Investigator-Assessed PFS for gCEAS
    ‹‹Ǥ ‡•‹–‹˜‹–›ƒŽ›•‹•
    ’—–ƒ–‹‘‘ˆ‹••‹‰ —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•”‹ƒ”›ƒƒŽ›•‹•ˆ‘”–Š‡‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡† 
    Š‡”‘„—•–‡••‘ˆ–Š‡•–—†› ‘ Ž—•‹‘•™ƒ•ƒ••‡••‡†„›‡˜ƒŽ—ƒ–‹‰–Š‡‹’ƒ –‘ˆ‹••‹‰
    —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•‘–Š‡‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡†‡˜‹ ‡ǤŠ‡‹••‹‰ —ƒ”†ƒ–͵͸Ͳ”‡•—Ž–•™‡”‡
    ‹’—–‡†‹–Š‡”ƒ†‘‹œ‡†ȋ–‹••—‡’‘•‹–‹˜‡Ȍ’‘’—Žƒ–‹‘—•‹‰ƒ‹’—–ƒ–‹‘‘†‡Ž—†‡”‹••‹‰
    ƒ–”ƒ†‘ƒ••—’–‹‘ǤŠ‡”‡ƒ”‡ͳͳͻȋ͵ͲͲȀͶͳͻǡʹͺΨȌ”ƒ†‘‹œ‡†’ƒ–‹‡–•‹͵™‹–Š

    ͷʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‹••‹‰ —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•ǡ‡ƒ Š‘ˆ–Š‡ͳͳͻ’ƒ–‹‡–•™‹–Š‹••‹‰ —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•
    ‹•–‘„‡‹’—–‡†˜‹ƒƒ•’‡ ‹ˆ‹‡†‘‰‹–‘†‡ŽǤƒ•‡Ž‹‡ ‘˜ƒ”‹ƒ–‡•‹ Ž—†‡†‹–Š‡‘‰‹–‘†‡Žƒ”‡ǣ
    x  ȋ‹‘–Š•ǡ’‘•–Ǧ„ƒ•‡Ž‹‡†ƒ–ƒȌ
    x ‰‡‰”‘—’ȋδ͸ͷ›‡ƒ”•ǡη͸ͷ›‡ƒ”•Ȍ
    x ƒ ‡ȋ•‹ƒǡ‘Ǧ•‹ƒȌ
    x ‘‹‰•–ƒ–—•ȋ‡˜‡”ǡ —””‡–Ȁˆ‘”‡”Ȍ
    x ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–—•‹‰’Žƒ•ƒ–‡•–”‡•—Ž–ȋ’‘•‹–‹˜‡ǡ‡‰ƒ–‹˜‡ǡˆƒ‹Ž‡†ǡ‘––‡•–‡†ǡ
    ‹••‹‰Ȍ
    ‡•—Ž–•„ƒ•‡†‘ͳǡͲͲͲ‹’—–ƒ–‹‘•ƒ”‡’”‡•‡–‡†‹Table 41ƒ†•Š‘™”‘„—•–ƒ† ‘•‹•–‡–
      „‡‡ˆ‹–‹–Š‡‰†‡ˆ‹‡†„›–Š‡‘„•‡”˜‡† —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•ƒ†–Š‡‰
    ȋ‘„•‡”˜‡†ƒ†‹’—–‡†Ȍǡ‹™Š‹ Š‹••‹‰ —ƒ”†ƒ–͵͸Ͳ–‡•–”‡•—Ž–•™‡”‡‹’—–‡†˜‹ƒ–Š‡
    •’‡ ‹ˆ‹‡†‘‰‹–‘†‡ŽǤŠ‡ ‘•‹•–‡ ›‘ˆ–Š‡•‡”‡•—Ž–•†‡‘•–”ƒ–‡•–Šƒ––Š‡‹••‹‰
    —ƒ”†ƒ–͵͸Ͳ†ƒ–ƒŠƒ˜‡‘‡ƒ‹‰ˆ—Ž‹’ƒ –‘–Š‡”‘„—•–‡••‘ˆ–Š‡‡ˆˆ‹ ƒ ›”‡•—Ž–‘„•‡”˜‡†‹
    –Š‡͵•–—†›Ǥ

    Table 41. Primary analysis for the investigator-assessed PFS for the gCEAS (observed) and
    gCEAS (observed and imputed)
     Comparison between treatments
    Number (%) of
    patients with 95% Confidence
    Population Treatment N events [a] Hazard Ratio Interval
    ‰    ͳ͵ͺ ͺͷȋ͸ͳǤ͸Ȍ
    ȋ‘„•‡”˜‡†Ȍ ͲǤ͵Ͷ ͲǤʹʹǡͲǤͷ͵
    Š‡‘–Š‡”ƒ’› ͷ͵ ͶͺȋͻͲǤ͸Ȍ
    ‰ȋ‘„•‡”˜‡†    ͳͺʹ ͳͲʹȋͷ͸ǤͲȌ
    ƒ†‹’—–‡†Ȍȏ„Ȑ Š‡‘–Š‡”ƒ’› ͲǤ͵ͷ ͲǤʹͶǡͲǤͷͳ
    ͻʹ ͹ͶȋͺͲǤͶȌ
    ȏƒȐ‘‰”ƒ‡–Š‘†™‹–Šƒ†Œ—•–‡–‘ˆ–Š‡•–—†›•–”ƒ–‹ˆ‹ ƒ–‹‘ˆƒ –‘”•‹•—•‡†ˆ‘”–Š‡ ‘’ƒ”‹•‘„‡–™‡‡–”‡ƒ–‡–•Ǥ
    ȏ„Ȑ ‘”‡ƒ Š‹’—–ƒ–‹‘ǡ–Š‡ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†—•‹‰ƒŽ‘‰”ƒ–‡•–•–”ƒ–‹ˆ‹‡†„›—–ƒ–‹‘•–ƒ–—•ƒ†”ƒ ‡ǤŠ‡
    ƒ˜‡”ƒ‰‡ ™‹–ŠͻͷΨ ˆ”‘ͳǡͲͲͲ‹’—–ƒ–‹‘•‹•’”‡•‡–‡†Ǥ

      ’—–ƒ–‹‘ƒŽ›•‹•–‘˜ƒŽ—ƒ–‡–Š‡ˆˆ‡ –‘ˆ„•‡”˜‡† —ƒ”†ƒ–͵͸ͲšǦ‹• ‘”†ƒ ‡


    ‹’—–ƒ–‹‘ƒƒŽ›•‹•‘†‡Ž‹‰–Š‡’‘–‡–‹ƒŽ‡ˆˆ‡ –‘ˆ —ƒ”†ƒ–͵͸ͲšǦ —ƒ”†ƒ–͵͸Ͳ
    †‹• ‘”†ƒ ‡‘–Š‡  ‘„•‡”˜‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•™ƒ• ‘†— –‡†ǤŠ‡
    •‡•‹–‹˜‹–›ƒƒŽ›•‹•„›‹’—–ƒ–‹‘ƒƒŽ›•‹•‘†‡ŽŽ‹‰™ƒ•’‡”ˆ‘”‡†ƒ ‘—–‹‰ˆ‘” ǤŠ‡
    ’‘–‡–‹ƒŽ‡ˆˆ‡ –‘ˆ —ƒ”†ƒ–͵͸ͲšǦ —ƒ”†ƒ–͵͸Ͳ†‹• ‘”†ƒ ‡‘–Š‡  ™ƒ• ƒŽ —Žƒ–‡†
    „›–Š‡‘‰”ƒ‘†‡ŽǤŠ‡‹†‡–‹–›„‡–™‡‡–Š‡‘„•‡”˜‡†‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡†  ‘ˆͲǤ͵Ͷ
    ȋͻͷΨ ͲǤʹʹǡͲǤͷ͵Ȍƒ†–Š‡‹’—–ƒ–‹‘”‡•—Ž–•ȋͲǤ͵ͶǡͻͷΨ ‘ˆ‹†‡ ‡ͲǤʹʹǡͲǤͷ͵Ȍ†‡‘•–”ƒ–‡•
    –Šƒ––Š‡Ž‡˜‡Ž‘ˆ‘„•‡”˜‡† —ƒ”†ƒ–͵͸ͲšǦ†‹• ‘”†ƒ ‡†‘‡•‘–‹’ƒ ––Š‡‘„•‡”˜‡†
    ”‡•—Ž–•ǤŠ‡•‡”‡•—Ž–••—’’‘”––Š‡ ‘„‹ƒ–‹‘‘ˆ†ƒ–ƒ†‡”‹˜‡†ˆ”‘ —ƒ”†ƒ–͵͸Ͳƒ†
    —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•Ǥ
    ‡•‹–‹˜‹–›ƒƒŽ›•‹•ˆ‘”–Š‡‹˜‡•–‹‰ƒ–‘”Ǧƒ••‡••‡† ‹–Š‡ —ƒ”†ƒ–͵͸Ͳ’‘•‹–‹˜‡’‘’—Žƒ–‹‘
    Š‡ƒƒŽ›•‹•ƒ„‘˜‡†‡‘•–”ƒ–‡†  ‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸ͲǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ’‘•‹–‹˜‡
    •—„•‡–‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ••Š‘™‹Table 42ǡ•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•‘†‡Ž‹‰‡ˆˆ‹ ƒ ›‹–Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘†‡‘•–”ƒ–‡•
    ”‘„—•–‡••–‘–Š‡ ‘–”‹„—–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’ƒ–‹‡–•‘–
    ”‡’”‡•‡–‡†‹–Š‡͵ Ž‹‹ ƒŽ•–—†›ǡ™‹–Š•–ƒ–‹•–‹ ƒŽŽ›Ǧ•‹‰‹ˆ‹ ƒ–‡ˆˆ‹ ƒ ›ƒ‹–ƒ‹‡†ƒ ”‘••
    –Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǡ‹ Ž—†‹‰–Š‡‘†‡Ž‡† —ƒ”†ƒ–͵͸ͲǦ

    ͷ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡•—„‰”‘—’ǤŠ‡ ƒŽ —Žƒ–‹‘•Š‘™‹Table 42ˆ‘”–Š‡’ƒ–‹‡–•
    • ”‡‡‡†‹͵—•‡†ƒ’”‡˜ƒŽ‡ ‡‘ˆͷͷΨǤ

    Table 42. Sensitivity Analysis for Investigator-Assessed PFS (Guardant360 positive


    irrespective of tissue result)
    Estimated
    P(Tissue+|Guardant360+) with
    95% CI Estimated HR (Guardant360+) with 95% CI
    Assumed HR
    PPV Point (Tissue- and
    Estimate 95% CI Guardant360+) Estimated HR 95% CI
    ‰ȋ‘„•‡”˜‡†Ȍ ͲǤ͹ʹ ͲǤ͸͸ǡͲǤ͹͹ ͲǤ͵Ͷ ͲǤ͵Ͷ ͲǤʹʹǡͲǤͷ͵
     ͲǤͷͲ ͲǤ͵ͺ ͲǤʹ͹ǡͲǤͷ͵
     ͲǤ͹ͷ ͲǤͶ͵ ͲǤ͵ͲǡͲǤ͸Ͳ
     ͳǤͲͲ ͲǤͶ͸ ͲǤ͵͵ǡͲǤ͸ͷ
    ‰ȋ‘„•‡”˜‡†Ϊ ͲǤ͹ʹ ͲǤ͸͸ǡͲǤ͹͹ ͲǤ͵ͷ ͲǤ͵͸ ͲǤʹͶǡͲǤͷͳ
    ‹’—–‡†Ȍ ͲǤͷͲ ͲǤ͵ͻ ͲǤʹͻǡͲǤͷʹ
    ͲǤ͹ͷ ͲǤͶ͵ ͲǤ͵ʹǡͲǤͷͻ
    ͳǤͲͲ ͲǤͶ͹ ͲǤ͵ͷǡͲǤ͸Ͷ
    ‘‰”ƒ‡–Š‘†™‹–Šƒ†Œ—•–‡–‘ˆ–Š‡•–—†›•–”ƒ–‹ˆ‹ ƒ–‹‘ˆƒ –‘”•‹•—•‡†–‘‡•–‹ƒ–‡ ™‹–ŠͻͷΨ ˆ‘”–Š‡’ƒ–‹‡–•‹
    –Š‡‰ȋ‘„•‡”˜‡†Ȍƒ†‰ȋ‘„•‡”˜‡†Ϊ‹’—–‡†ȌǤ

    ‹‹‹Ǥ ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳƒ†–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–•‹‰‹••—‡


    ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳǡi.e.ǡ —ƒ”†ƒ–͵͸Ͳšƒ†–‡•–˜‡”•‹‘•”‡•—Ž–•
    ‘„‹‡†ƒ†–Š‡ ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–—•‹‰–‹••—‡ˆ‘”ƒŽŽƒ– Š‡†’Žƒ•ƒǦ–‹••—‡•ƒ’Ž‡•
    ˆ”‘–Š‡͵•–—†›‹••Š‘™‹Table 43Ǥ

    Table 43. Concordance between Guardant360 and the cobas ® EGFR Mutation Test Using Tissue
    EGFR T790M cobas® EGFR Mutation Test Using Tissue
    Positive Negative Failed Total
    Guardant360    
    ‘•‹–‹˜‡ ͳͻͲ Ͷͺ Ͳ ʹ͵ͺ
    ‡‰ƒ–‹˜‡ ͻʹ ͻͺ Ͳ ͳͻͲ
    ƒ‹Ž‡† ͳͷ Ͷ Ͳ ͳͻ
    ‘–ƒŽ ʹͻ͹ ͳͷͲȏ„Ȑ Ͳ ͶͶ͹
    ȋͻͷΨ ȌȏƒȐ ͸͹ǤͶΨȏ͸ͳǤ͸Ȃ͹ʹǤͺΨȐ
    ȋͻͷΨ ȌȏƒȐ ͸͹ǤͳΨȏͷͺǤͻȂ͹ͶǤ͹ΨȐ
    ȏƒȐƒ†™‹–ŠͻͷΨ •ƒ”‡ ƒŽ —Žƒ–‡†„ƒ•‡†‘˜ƒŽ‹†–‡•–”‡•—Ž–•ȋ’‘•‹–‹˜‡‘”‡‰ƒ–‹˜‡ȌǤŠ‡ͻͷΨ‡šƒ –ȋŽ‘’’‡”Ǧ
    ‡ƒ”•‘Ȍ ‹• ƒŽ —Žƒ–‡†Ǥȏ„Ȑ  Ž—†‡•ʹ’ƒ–‹‡–•‡‰ƒ–‹˜‡ˆ‘”EGFR͹ͻͲ”ƒ†‘‹œ‡†‹–‘–Š‡ ‹‡””‘”Ǥ
    ‘ ‘”†ƒ ‡”‡Žƒ–‹˜‡–‘ —ƒ”†ƒ–͵͸ͲšƒŽ‘‡‹••‹‹Žƒ”ǤŠ‡’‘‹–‡•–‹ƒ–‡•‘ˆƒ†
    ƒ† ‘””‡•’‘†‹‰ͻͷΨ •ˆ‘”EGFR͹ͻͲƒ”‡͸͸ǤͻΨȋ͸ͲǤ͹Ψǡ͹ʹǤͺΨȌƒ†͸͹ǤͳΨȋͷͺǤͻΨǡ
    ͹ͶǤ͹ΨȌ”‡•’‡ –‹˜‡Ž›Ǥ

    ͹Ǥ͵Ǥ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”EGFR‡š‘ʹͲ •‡”–‹‘•


    ‹ƒ‰‘•–‹ –—†›‡•‹‰
    Š‹•†‹ƒ‰‘•–‹ •–—†›—•‡•„ƒ‡†•ƒ’Ž‡•ˆ”‘–Š‡  ȋ ƒ••‡ ͳͲͲͳ‘”
    ͸ͳͳͺ͸͵͹ʹ ͳͲͲͳȌ Ž‹‹ ƒŽ•–—†›ȋͲʹ͸Ͳͻ͹͹͸Ȍ‹–Š‡ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›ǤŠ‡’”‹ƒ”›
    ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ ‘’”‹•‡•ͺͳ•—„Œ‡ –•ˆ”‘–Š‡   Ž‹‹ ƒŽ•–—†›
    ™‹–Š ‡š‘ʹͲ‹•‡”–‹‘•ƒ•†‡–‡”‹‡†„›Ž‘ ƒŽ–‡•–”‡•—Ž–•ǡ™Š‘•‡†‹•‡ƒ•‡’”‘‰”‡••‡†‘‘”
    ͷͶ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ƒˆ–‡”’Žƒ–‹—Ǧ„ƒ•‡† Š‡‘–Š‡”ƒ’›ǡƒ†™Š‘™‡”‡–”‡ƒ–‡†™‹–Š–Š‡”‡ ‘‡†‡†’Šƒ•‡ʹ†‘•‡
    ȋʹȌ‘ˆƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™ǤŠ‡„ƒ‡†’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘–Š‡•‡•—„Œ‡ –•™‡”‡
    ”‡–”‘•’‡ –‹˜‡Ž›–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸ͲšǤ
    •–Š‡ƒŒ‘”‹–›ȋ͹ͷȀͺͳǡͻʹǤ͸ΨȌ‘ˆ•—„Œ‡ –•‹ Ž—†‡†‹–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘
    ’‘’—Žƒ–‹‘™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘’‘•‹–‹˜‡Ž‘ ƒŽ–‹••—‡–‡•–‹‰ˆ‘”EGFR‡š‘ʹͲ‹•‡”–‹‘•ǡ
    •‡•‹–‹˜‹–›ƒƒŽ›•‹•–‘ƒ••‡••–Š‡’‘••‹„Ž‡‹ˆŽ—‡ ‡‘ˆŽ‘ ƒŽ–‡•–Ǧ‡‰ƒ–‹˜‡ǡ —ƒ”†ƒ–͵͸Ͳ’Žƒ•ƒǦ
    ’‘•‹–‹˜‡’ƒ–‹‡–•ȋ —ƒ”†ƒ–͵͸ͲšΪŽ‘ ƒŽ–‡•–ȂȌ™ƒ•’‡”ˆ‘”‡†—•‹‰ͺ͵˜ƒŽ‹†”‡•—Ž–•ˆ”‘ͺͷ
    •—’’Ž‡‡–ƒŽ•ƒ’Ž‡•ˆ”‘–Š‡‘ǦEGFR‡š‘ʹͲ‹•‡”–‹‘ƒ”•‘ˆ–Š‡   Ž‹‹ ƒŽ•–—†›
    • ”‡‡ˆƒ‹Ž’‘’—Žƒ–‹‘ƒ†ƒƒ††‹–‹‘ƒŽͺͺ˜ƒŽ‹†”‡•—Ž–•ˆ”‘ͻʹ•ƒ’Ž‡•ˆ”‘–Š‡ Ž‹‹ ƒŽ
    –—†›Ǥ
    ”‹ƒ”›Ž‹‹ ƒŽ–—†›‘’—Žƒ–‹‘
    Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ ‘’”‹•‡•EGFR‡š‘ʹͲ‹•‡”–‹‘
    —–ƒ–‹‘Ǧ’‘•‹–‹˜‡•—„Œ‡ –•ˆ”‘–Š‡  •–—†›™Š‘•‡†‹•‡ƒ•‡’”‘‰”‡••‡†‘‘”ƒˆ–‡”
    ’Žƒ–‹—Ǧ„ƒ•‡† Š‡‘–Š‡”ƒ’›ƒ†™Š‘™‡”‡–”‡ƒ–‡†™‹–Š–Š‡ʹ‘ˆƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™Ǥ—„Œ‡ –•
    —•–Šƒ˜‡”‡ ‡‹˜‡†–Š‡ˆ‹”•–†‘•‡‘ˆƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™ƒ•‘‘–Š‡”ƒ’›‘‘”„‡ˆ‘”‡Ͳͷ ‡„”—ƒ”›
    ʹͲʹͲƒ†™‡”‡–‘Šƒ˜‡—†‡”‰‘‡ƒ–Ž‡ƒ•–͵• Š‡†—Ž‡†’‘•–Ǧ„ƒ•‡Ž‹‡†‹•‡ƒ•‡ƒ••‡••‡–•‘”
    †‹• ‘–‹—‡†–”‡ƒ–‡–ˆ‘”ƒ›”‡ƒ•‘ǡ‹ Ž—†‹‰†‹•‡ƒ•‡’”‘‰”‡••‹‘ƒ†Ȁ‘”†‡ƒ–Šǡ’”‹‘”–‘–Š‡
    Ž‹‹ ƒŽ†ƒ–ƒ —–Ǧ‘ˆˆǤ
    ”‡–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•™‡”‡ ‘ŽŽ‡ –‡†ˆ”‘•—„Œ‡ –•‹–”‡  ˆ•ƒ†–‡•–‡†
    ”‡–”‘•’‡ –‹˜‡Ž›—•‹‰ —ƒ”†ƒ–͵͸Ͳšƒˆ–‡”–Š‡ ‘’Ž‡–‹‘‘ˆ–Š‡  •–—†›Ǥ
    —’’Ž‡‡–ƒŽ‘’—Žƒ–‹‘•ˆ‘”Žƒ•ƒǦ‹••—‡ƒŽ›•‹•
    ‹ ‡–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ ‘•‹•–•’”‹ƒ”‹Ž›‘ˆ•—„Œ‡ –•’‘•‹–‹˜‡
    ˆ‘” ‡š‘ʹͲ‹•‡”–‹‘•„›Ž‘ ƒŽ–‹••—‡–‡•–‹‰ǡƒ††‹–‹‘ƒŽ•—„Œ‡ –•™‡”‡”‡“—‹”‡†–‘‡˜ƒŽ—ƒ–‡–Š‡
    Ž‘ ƒŽ–‡•–Ǧ‡‰ƒ–‹˜‡’‘”–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲšΪ‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ‘–Š‹•‡†ǡ• ”‡‡ˆƒ‹Ž
    •—„Œ‡ –•ˆ”‘–Š‡‘ǦEGFR‡š‘ʹͲ‹•‡”–‹‘• ‘Š‘”–•‘ˆ   Ž‹‹ ƒŽ•–—†›–‡•–‡†™‹–Š„‘–Š
    —ƒ”†ƒ–͵͸Ͳšƒ†–‹••—‡Ǧ„ƒ•‡†  ‡–”ƒŽ–‡•–‹‰ƒ•™‡ŽŽƒ•’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡† Ž‹‹ ƒŽ•ƒ’Ž‡
    †ƒ–ƒˆ”‘•—„Œ‡ –•‡”‘ŽŽ‡†‹–Š‡‘‹˜ƒ•‹˜‡˜•Ǥ ˜ƒ•‹˜‡—‰˜ƒŽ—ƒ–‹‘ȋ Ȍ•–—†›
    ȋͲ͵͸ͳͷͶͶ͵Ȍ™‡”‡—•‡†Ǥ
    Ž‹‹ ƒŽ’‡ ‹‡‡Ž‡ –‹‘”‹–‡”‹ƒ
    ŽŽ•—„Œ‡ –•‡”‘ŽŽ‡†‹–Š‡’”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ˆ‘”–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™
    ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ǡ™‡”‡‹ Ž—†‡†‹–Š‡†‹ƒ‰‘•–‹ •–—†›‡ˆˆ‹ ƒ › ‘Š‘”–‹ˆ–Š‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ
    „‡Ž‘™ƒ”‡‡–Ǥ‹‹Žƒ”Ž›ǡƒŽŽ•—„Œ‡ –•‡‡–‹‰–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†› ‘Š‘”–
    •‡Ž‡ –‹‘ ”‹–‡”‹ƒ„‡Ž‘™ƒ”‡‹ Ž—†‡†Ǥ
    —ƒ”†ƒ–͵͸Ͳš‹ƒ‰‘•–‹ –—†›ˆˆ‹ ƒ ›‘Š‘”–ƒ–‹‡–  Ž—•‹‘”‹–‡”‹ƒ
    x —„Œ‡ –‡”‘ŽŽ‡†‹–Š‡   Ž‹‹ ƒŽ•–—†›™‹–Š‹ˆ‘”‡† ‘•‡–ˆ‘”„Ž‘‘†•ƒ’Ž‡—•‡
    ˆ‘”ˆ—”–Š‡””‡•‡ƒ” ŠǤ
    x —„Œ‡ –’ƒ”–‘ˆ–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘Ǥ
    x †‡“—ƒ–‡’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘” —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰‘”ƒ’”‡˜‹‘—•Ž›
    ‰‡‡”ƒ–‡† —ƒ”†ƒ–͵͸Ͳš–‡•–”‡•—Ž–ˆ”‘–Š‡ͲͳǦǦͲͲ͹•–—†›

    ͷͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    —ƒ”†ƒ–͵͸Ͳš‹ƒ‰‘•–‹ –—†›‡•‹–‹˜‹–›ƒŽ›•‹•”‡˜ƒŽ‡ ‡—„Ǧ–—†›‘Š‘”–ƒ–‹‡–
     Ž—•‹‘”‹–‡”‹ƒ
     ”‡‡ ƒ‹Žƒ’Ž‡•ˆ”‘–Š‡  Ž‹‹ ƒŽ–—†›
    x —„Œ‡ –ˆƒ‹Ž‡†• ”‡‡‹‰ˆ‘”–Š‡   Ž‹‹ ƒŽ•–—†›™‹–Š‹ˆ‘”‡† ‘•‡–ˆ‘”„Ž‘‘†
    •ƒ’Ž‡—•‡ˆ‘”ˆ—”–Š‡””‡•‡ƒ” ŠǤ
    x ”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–‡•–‹‰™‹–Š —ƒ”†ƒ–͵͸Ͳš‘”ƒ —ƒ”†ƒ–͵͸Ͳ
    š–‡•–”‡•—Ž–’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†—†‡”–Š‡ —ƒ”†ƒ– ‡ƒŽ–ŠͲͳǦǦͲͲ͹’”‘–‘ ‘ŽǤ
    x ˜ƒ‹Žƒ„‹Ž‹–›‘ˆ’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†   Ž‹‹ ƒŽ•–—†› ‡–”ƒŽ–‹••—‡–‡•–‹‰”‡•—Ž–•Ǥ
    ƒ’Ž‡•ˆ”‘–Š‡ Ž‹‹ ƒŽ–—†›
    x —„Œ‡ –•‡”‘ŽŽ‡†‹–Š‡  Ž‹‹ ƒŽ•–—†›™‹–Š†‘ —‡–‡†‹ˆ‘”‡† ‘•‡–Ǥ
    x ˜ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš–‡•–”‡•—Ž–’”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†ˆ”‘ƒ’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡
    —†‡”–Š‡ͲͳǦǦͲͲ͵•–—†›Ǥ
    x ”‡˜‹‘—•Ž›‰‡‡”ƒ–‡†˜ƒŽ‹†–‡•–”‡•—Ž–ˆ”‘ ‘„ƒ•EGFR—–ƒ–‹‘‡•–˜ʹ–‡•–‹‰‘–‹••—‡
    •Ž‹†‡•ƒ†Ȁ‘”ƒ–‹••—‡„Ž‘ ‘ˆˆ‘”ƒŽ‹Ǧˆ‹š‡†’ƒ”ƒˆˆ‹Ǧ‡„‡††‡†–‹••—‡™‹–Š•—ˆˆ‹ ‹‡––—‘”
    ‘–‡–ƒ†“—ƒ–‹–›ˆ‘”–‡•–‹‰ƒ•†‡ˆ‹‡†„›–Š‡ ‡–”ƒŽ–‡•–‹‰”‡“—‹”‡‡–•ˆ‘”–Š‡ͲͳǦǦ
    ͲͲ͵•–—†›Ǥ
    ‹ƒ‰‘•–‹ –—†›”‹ƒ”›„Œ‡ –‹˜‡ƒ††’‘‹–
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†›‹•–‘†‡‘•–”ƒ–‡–Š‡ ‘’ƒ”ƒ„‹Ž‹–›‘ˆ•‹‰Ž‡Ǧƒ‰‡–
    ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™‡ˆˆ‹ ƒ ›‹–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘•—„Œ‡ –•™Š‘
    ƒ”‡’‘•‹–‹˜‡ˆ‘”EGFR‡š‘ʹͲ‹•‡”–‹‘•„› —ƒ”†ƒ–͵͸Ͳš–‘–Š‡•‹œ‡Ǧƒ†Œ—•–‡†—ŽŽŠ›’‘–Š‡•‹•
    ‡ˆˆ‹ ƒ › ‹–‡†‹–Š‡   Ž‹‹ ƒŽ•–—†›’”‘–‘ ‘ŽǤŠ‡’”‹ƒ”›‡†’‘‹–‹•‘„Œ‡ –‹˜‡”‡•’‘•‡
    ”ƒ–‡ȋȌ„› ͳǤͳƒ•ƒ••‡••‡†„›„Ž‹†‡†‹†‡’‡†‡– ‡–”ƒŽ”‡˜‹‡™ȋ  Ǥ
    ‡•‹–‹˜‹–›ƒƒŽ›•‡•™‡”‡ ‘†— –‡†–‘‘†‡Ž–Š‡‹’ƒ –‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš ΪŽ‘ ƒŽ–‡•–Ȃ
    ’‘’—Žƒ–‹‘ƒ†•—„Œ‡ –•™‹–Š‘—– —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•Ǥ
     ‘—–ƒ„‹Ž‹–›‘ˆ•–—†›•—„Œ‡ –•
    Š‡†‹ƒ‰‘•–‹ •–—†› ‘’”‹•‡•ͺͳ•—„Œ‡ –•‘ˆ–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘
    ’‘’—Žƒ–‹‘ȋFigure 6ȌǤˆ–Š‡͹ͺ•—„Œ‡ –•ȋͻ͸ΨȌ™‹–Š•ƒ’Ž‡•ƒ˜ƒ‹Žƒ„Ž‡ˆ‘”–‡•–‡†„›–Š‡ —ƒ”†ƒ–͵͸Ͳ
    šǡ͸Ͷ•—„Œ‡ –•ȋͺʹΨȌ–‡•–‡†’‘•‹–‹˜‡„›–Š‡ —ƒ”†ƒ–͵͸Ͳš™‡”‡‹ Ž—†‡†‹–Š‡’”‹ƒ”›
    ‘„Œ‡ –‹˜‡ƒƒŽ›•‹••‡–ǡ™Š‹Ž‡ͳͶ•—„Œ‡ –•ȋͳͺΨȌ–‡•–‡†‡‰ƒ–‹˜‡ǡƒ†Ͳ•—„Œ‡ –•ȋͲΨȌˆƒ‹Ž‡†–‡•–‹‰Ǥ
    Š”‡‡•—„Œ‡ –•ȋ͵Ǥ͹Ψ‘ˆ–Š‡’”‹ƒ”›‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘Ȍ•—„Œ‡ –•†‹†‘–Šƒ˜‡’Žƒ•ƒ•ƒ’Ž‡•ˆ‘”
    –‡•–‹‰Ǥ

    ͷ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    
    Figure 6. Guardant360 CDx Clinical Efficacy Analyses Subject Disposition
    ‹ƒ‰‘•–‹ –—†›ˆˆ‹ ƒ ›‘’—Žƒ–‹‘‡’”‡•‡–ƒ–‹˜‡‡••‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡Ž‹‹ ƒŽ
    Šƒ”ƒ –‡”‹•–‹ •
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ•—„Œ‡ –•‡”‘ŽŽ‡†‹–Š‡   Ž‹‹ ƒŽ
    •–—†›™‡”‡ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡–‘–Š‡†‹ƒ‰‘•–‹ •–—†›’‘’—Žƒ–‹‘•ƒ•†‡ˆ‹‡†„› —ƒ”†ƒ–͵͸Ͳš
    ”‡•—Ž–•Ǥ••Š‘™‹Table 44 ƒ†Table 45ǡ–Š‡†‹ƒ‰‘•–‹ •–—†›‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ȋ‰Ȍ
    †‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ • Ž‘•‡Ž›”‡•‡„Ž‡–Š‘•‡‘ˆ–Š‡‘˜‡”ƒŽŽ’”‹ƒ”›
    ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ȋ ȌǤ
    ‘ƒ••‡••’‘–‡–‹ƒŽ„‹ƒ•ƒ”‹•‹‰ˆ”‘’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„‹Ž‹–›ǡ†‡‘‰”ƒ’Š‹ ‹ˆ‘”ƒ–‹‘ƒ†
    „ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ–Š‡‰ƒ†–Š‡‰Ǧ™‡”‡ ‘’ƒ”‡†ƒ†–Š‡ƒ••‘ ‹ƒ–‡†’˜ƒŽ—‡
    ”‡’‘”–‡†‹Table 44ƒ†Table 45Ǥ‘‡ƒ‹‰ˆ—Ž†‹ˆˆ‡”‡ ‡•™‡”‡‘„•‡”˜‡†Ǥ

    Table 44. Comparison of Clinical Effectiveness Analysis Subgroup Demographics


    p Value
    gAS- gAS-F gAS vs
    CHRYSALIS FAS gAS gNT gCEAS gAS- F +gNT gAS-Unk
    ƒŽ›•‹••‡–ǣ ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ǧ ͵

    ‰‡ǡ›‡ƒ”•
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͻͳͶ
    ‡ƒȋȌ ͸ʹǤ͵ȋͻǤͻ͸Ȍ ͸ʹǤ͵ ͸ͳǤ͹ ͸ʹǤͳ ͸͵Ǥʹ Ǧ ͸ͳǤ͹
    ȋͳͲǤͲͶȌ ȋͻǤʹͻȌ ȋͳͲǤͳ͵Ȍ ȋͻǤͻͶȌ ȋͻǤʹͻȌ
    ‡†‹ƒ ͸ʹǤͲ ͸ʹǤͲ ͷͻǤͲ ͸ͳǤͷ ͸͸Ǥͷ Ǧ ͷͻǤͲ
    ƒ‰‡ ȋͶʹǢͺͶȌ ȋͶʹǢͺͶȌ ȋͷͶǢ͹ʹȌ ȋͶʹǢͺͶȌ ȋͶ͸Ǣ͹͸Ȍ Ǧ ȋͷͶǢ͹ʹȌ
    δ͸ͷ ͶͺȋͷͻǤ͵ΨȌ Ͷ͸ ʹȋ͸͸Ǥ͹ΨȌ ͶͲ ͸ Ǧ ʹȋ͸͸Ǥ͹ΨȌ
    ȋͷͻǤͲΨȌ ȋ͸ʹǤͷΨȌ ȋͷ͹ǤͳΨȌ
    εα͸ͷ ͵͵ȋͶͲǤ͹ΨȌ ͵ʹ ͳȋ͵͵Ǥ͵ΨȌ ʹͶ ͺ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͶͳǤͲΨȌ ȋ͵͹ǤͷΨȌ ȋͷ͹ǤͳΨȌ
    δ͹ͷ ͹ͶȋͻͳǤͶΨȌ ͹ͳ ͵ ͷͺ ͳ͵ Ǧ ͵
    ȋͻͳǤͲΨȌ ȋͳͲͲǤͲΨȌ ȋͻͲǤ͸ΨȌ ȋͻʹǤͻΨȌ ȋͳͲͲǤͲΨȌ
    εα͹ͷ ͹ȋͺǤ͸ΨȌ ͹ȋͻǤͲΨȌ Ͳ ͸ȋͻǤͶΨȌ ͳȋ͹ǤͳΨȌ Ǧ Ͳ
    
    ‡š
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͳǤͲͲͲ
    ‡ƒŽ‡ ͶͺȋͷͻǤ͵ΨȌ Ͷ͸ ʹȋ͸͸Ǥ͹ΨȌ ͶͲ ͸ Ǧ ʹȋ͸͸Ǥ͹ΨȌ
    ȋͷͻǤͲΨȌ ȋ͸ʹǤͷΨȌ ȋͶʹǤͻΨȌ
    ƒŽ‡ ͵͵ȋͶͲǤ͹ΨȌ ͵ʹ ͳȋ͵͵Ǥ͵ΨȌ ʹͶ ͺ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͶͳǤͲΨȌ ȋ͵͹ǤͷΨȌ ȋͷ͹ǤͳΨȌ

    ͷ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    p Value
    gAS- gAS-F gAS vs
    CHRYSALIS FAS gAS gNT gCEAS gAS- F +gNT gAS-Unk
    ƒ ‡
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͳͲͶ
    •‹ƒ ͶͲȋͶͻǤͶΨȌ ͵ͻ ͳȋ͵͵Ǥ͵ΨȌ ͵͸ ͵ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͷͲǤͲΨȌ ȋͷ͸Ǥ͵ΨȌ ȋʹͳǤͶΨȌ
    Žƒ ‘”ˆ”‹ ƒ ʹȋʹǤͷΨȌ ͳȋͳǤ͵ΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͳȋͳǤ͸ΨȌ Ͳ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ‡”‹ ƒ
    Š‹–‡ ͵Ͳȋ͵͹ǤͲΨȌ ʹͻ ͳȋ͵͵Ǥ͵ΨȌ ʹͳ ͺ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋ͵͹ǤʹΨȌ ȋ͵ʹǤͺΨȌ ȋͷ͹ǤͳΨȌ
    ‘–”‡’‘”–‡† ͻȋͳͳǤͳΨȌ ͻȋͳͳǤͷΨȌ Ͳ ͸ȋͻǤͶΨȌ ͵ Ǧ Ͳ
    ȋʹͳǤͶΨȌ

    –Š‹ ‹–›
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͳǤͲͲͲ
    ‹•’ƒ‹ ‘”ƒ–‹‘ ͵ȋ͵Ǥ͹ΨȌ ͵ȋ͵ǤͺΨȌ Ͳ ͵ȋͶǤ͹ΨȌ Ͳ Ǧ Ͳ
    ‘– ‹•’ƒ‹ ‘” ͸ͺȋͺͶǤͲΨȌ ͸ͷ ͵ ͷͷ ͳͲ Ǧ ͵
    ƒ–‹‘ ȋͺ͵Ǥ͵ΨȌ ȋͳͲͲǤͲΨȌ ȋͺͷǤͻΨȌ ȋ͹ͳǤͶΨȌ ȋͳͲͲǤͲΨȌ
    ‘–”‡’‘”–‡† ͳͲȋͳʹǤ͵ΨȌ ͳͲ Ͳ ͸ȋͻǤͶΨȌ Ͷ Ǧ Ͳ
    ȋͳʹǤͺΨȌ ȋʹͺǤ͸ΨȌ

    ‡‹‰Š–ǡ‰
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͷ͸͵
    ‡ƒȋȌ ͸͹ǤͶͻ ͸͹Ǥʹͺ ͹͵ǤͲ͵ ͸ͷǤ͵ʹ ͹͸ǤʹͶ Ǧ ͹͵ǤͲ͵
    ȋͳ͸Ǥ͹ͺͶȌ ȋͳ͸ǤͶͲ͹Ȍ ȋʹͻǤʹͷͺȌ ȋͳ͸ǤͲ͵͵Ȍ ȋͳͷǤͷͻ͸Ȍ ȋʹͻǤʹͷͺȌ
    ‡†‹ƒ ͸ʹǤͷͲ ͸ʹǤͻͷ ͷ͹ǤͳͲ ͸ͳǤ͸Ͳ ͹͵Ǥ͸Ͳ Ǧ ͷ͹ǤͳͲ
    ƒ‰‡ ȋ͵ͷǤͶǢ ȋ͵ͷǤͶǢ ȋͷͷǤʹǢ ȋ͵ͷǤͶǢ ȋͷʹǤͲǢ Ǧ ȋͷͷǤʹǢ
    ͳͳͷǤͲȌ ͳͳͷǤͲȌ ͳͲ͸ǤͺȌ ͳͲ͸ǤʹȌ ͳͳͷǤͲȌ ͳͲ͸ǤͺȌ

    ‡‹‰Š–ǡ 
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͷͲͶ
    ‡ƒȋȌ ͳ͸͵Ǥ͹ͳ ͳ͸͵ǤͺͶ ͳ͸ͲǤʹ͹ ͳ͸͵Ǥͳ͸ ͳ͸͸Ǥͻ͹ Ǧ ͳ͸ͲǤʹ͹
    ȋͻǤͲʹͲȌ ȋͻǤͲͶͶȌ ȋͻǤʹͻͷȌ ȋͻǤʹ͸ͲȌ ȋ͹ǤͶͻͳȌ ȋͻǤʹͻͷȌ
    ‡†‹ƒ ͳ͸ʹǤ͸Ͳ ͳ͸ʹǤ͹ͷ ͳͷͶǤͻͲ ͳ͸ͲǤͷͷ ͳ͸͸Ǥ͹Ͳ Ǧ ͳͷͶǤͻͲ
    ƒ‰‡ ȋͳͶͶǤͷǢ ȋͳͶͶǤͷǢ ȋͳͷͶǤͻǢ ȋͳͶͶǤͷǢ ȋͳͷͲǤͲǢ Ǧ ȋͳͷͶǤͻǢ
    ͳͻʹǤͲȌ ͳͻʹǤͲȌ ͳ͹ͳǤͲȌ ͳͻʹǤͲȌ ͳ͹͸Ǥ͸Ȍ ͳ͹ͳǤͲȌ

    ‘†›ƒ••‹†‡šǡ‰Ȁʹ
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤ͵ʹͲ
    ‡ƒȋȌ ʹͶǤͻͻ͵ ʹͶǤͺͺ͸ ʹ͹Ǥ͹͹͸ ʹͶǤ͵͸ͺ ʹ͹ǤʹͷͶ Ǧ ʹ͹Ǥ͹͹͸
    ȋͶǤͻͲͶ͹Ȍ ȋͶǤͺͳͷͳȌ ȋ͹Ǥͷͺ͸͸Ȍ ȋͶǤ͹ʹ͹ͲȌ ȋͶǤ͸ͷ͹ʹȌ ȋ͹Ǥͷͺ͸͸Ȍ
    ‡†‹ƒ ʹͶǤʹͷͲ ʹͶǤͷͲͺ ʹ͵Ǥ͹ͻͺ ʹ͵ǤͶͷͷ ʹͷǤͺͷͺ Ǧ ʹ͵Ǥ͹ͻͺ
    ƒ‰‡ ȋͳͶǤͲͲǢ ȋͳͶǤͲͲǢ ȋʹ͵ǤͲͳǢ ȋͳͶǤͲͲǢ ȋͳͻǤͷ͹Ǣ Ǧ ȋʹ͵ǤͲͳǢ
    ͵͸Ǥͺ͹Ȍ ͵͸Ǥͺ͹Ȍ ͵͸ǤͷʹȌ ͵͸Ǥ͹ʹȌ ͵͸Ǥͺ͹Ȍ ͵͸ǤͷʹȌ
    †‡”™‡‹‰Š–δͳͺǤͷ ͶȋͶǤͻΨȌ ͶȋͷǤͳΨȌ Ͳ Ͷȋ͸Ǥ͵ΨȌ Ͳ Ǧ Ͳ
    ‘”ƒŽͳͺǤͷǦδʹͷ Ͷ͵ȋͷ͵ǤͳΨȌ Ͷͳ ʹȋ͸͸Ǥ͹ΨȌ ͵͸ ͷ Ǧ ʹȋ͸͸Ǥ͹ΨȌ
    ȋͷʹǤ͸ΨȌ ȋͷ͸Ǥ͵ΨȌ ȋ͵ͷǤ͹ΨȌ
    ˜‡”™‡‹‰Š–ʹͷǦδ͵Ͳ ʹͳȋʹͷǤͻΨȌ ʹͳ Ͳ ͳ͸ ͷ Ǧ Ͳ
    ȋʹ͸ǤͻΨȌ ȋʹͷǤͲΨȌ ȋ͵ͷǤ͹ΨȌ
    „‡•‡εα͵Ͳ ͳ͵ȋͳ͸ǤͲΨȌ ͳʹ ͳȋ͵͵Ǥ͵ΨȌ ͺ Ͷ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͳͷǤͶΨȌ ȋͳʹǤͷΨȌ ȋʹͺǤ͸ΨȌ
    
    ͷͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    p Value
    gAS- gAS-F gAS vs
    CHRYSALIS FAS gAS gNT gCEAS gAS- F +gNT gAS-Unk
    ‘ ƒŽ‡•–›’‡ȗ
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͺͲ͵
     ȋŽ‘‘†Ȍ ͶȋͶǤͻΨȌ ͶȋͷǤͳΨȌ Ͳ ͵ȋͶǤ͹ΨȌ ͳȋ͹ǤͳΨȌ Ǧ Ͳ
     ȋ‹••—‡Ȍ ͵ͶȋͶʹǤͲΨȌ ͵͵ ͳȋ͵͵Ǥ͵ΨȌ ʹͶ ͻ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͶʹǤ͵ΨȌ ȋ͵͹ǤͷΨȌ ȋ͸ͶǤ͵ΨȌ
     ȋŽ‘‘†Ȍ ͳȋͳǤʹΨȌ ͳȋͳǤ͵ΨȌ Ͳ ͳȋͳǤ͸ΨȌ Ͳ Ǧ Ͳ
     ȋ‹••—‡Ȍ ͹ȋͺǤ͸ΨȌ ͹ȋͻǤͲΨȌ Ͳ ͹ Ͳ Ǧ Ͳ
    ȋͳͲǤͻΨȌ
    ȋŽ‘‘†Ȍ ͳȋͳǤʹΨȌ ͳȋͳǤ͵ΨȌ Ͳ ͳȋͳǤ͸ΨȌ Ͳ Ǧ Ͳ
    ȋ‹••—‡Ȍ ͵Ͳȋ͵͹ǤͲΨȌ ʹͺ ʹȋ͸͸Ǥ͹ΨȌ ʹͷ ͵ Ǧ ʹȋ͸͸Ǥ͹ΨȌ
    ȋ͵ͷǤͻΨȌ ȋ͵ͻǤͳΨȌ ȋʹͳǤͶΨȌ
    ȋ‹••—‡Ȍ ͶȋͶǤͻΨȌ ͶȋͷǤͳΨȌ Ͳ ͵ȋͶǤ͹ΨȌ ͳȋ͹ǤͳΨȌ Ǧ Ͳ

    ȗ‘ ƒŽ–‡•––›’‡ƒ•†‡ˆ‹‡†„›–Š‡‡”‘ŽŽ‹‰•‹–‡Ǥ
    ǣ —ŽŽƒŽ›•‹•‡–ǡ‰ǣ —ƒ”†ƒ–͵͸ͲšƒƒŽ›•‹••‡–ǡ‰ǣ —ƒ”†ƒ–͵͸Ͳš‘––‡•–‡†•‡–ǡ
    ‰ǣ —ƒ”†ƒ–͵͸Ͳš’”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›ƒƒŽ›•‹••‡–ǡ‰ǣ —ƒ”†ƒ–͵͸ͲšƒƒŽ›•‹••‡–ǡ
    ‰Ǧ ǣ —ƒ”†ƒ–͵͸ͲšƒƒŽ›•‹••‡–ˆƒ‹Ž‡†ǡ‰Ǧǣ —ƒ”†ƒ–͵͸Ͳš—‘™•‡–

    Table 45. Comparison of Clinical Effectiveness Analysis Sub-Group Baseline Clinical


    Characteristics.
    p Value
    gAS vs
    CHRYSALIS FAS gAS gNT gCEAS gAS- gAS-F gAS-Unk gAS-Unk
    ƒŽ›•‹••‡–ǣ ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ǧ ͵
    ‹–‹ƒŽ†‹ƒ‰‘•‹•
    •—„–›’‡
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͻʹʹ
    †‡‘ ƒ” ‹‘ƒ ͹͹ȋͻͷǤͳΨȌ ͹ͶȋͻͶǤͻΨȌ ͵ ͸ͳ ͳ͵ Ǧ ͵
    ȋͳͲͲǤͲΨȌ ȋͻͷǤ͵ΨȌ ȋͻʹǤͻΨȌ ȋͳͲͲǤͲΨȌ
    ƒ”‰‡ ‡ŽŽ Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
    ƒ” ‹‘ƒ
    “—ƒ‘—• ‡ŽŽ ͵ȋ͵Ǥ͹ΨȌ ͵ȋ͵ǤͺΨȌ Ͳ ʹȋ͵ǤͳΨȌ ͳȋ͹ǤͳΨȌ Ǧ Ͳ
    ƒ” ‹‘ƒ
    –Š‡” ͳȋͳǤʹΨȌ ͳȋͳǤ͵ΨȌ Ͳ ͳȋͳǤ͸ΨȌ Ͳ Ǧ Ͳ
    ‘–”‡’‘”–‡† Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
    ‹•–‘Ž‘‰›‰”ƒ†‡ƒ–
    ‹‹–‹ƒŽ†‹ƒ‰‘•‹•
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤ͹Ͳͺ
    ‘†‡”ƒ–‡Ž› ͳͺȋʹʹǤʹΨȌ ͳ͹ȋʹͳǤͺΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͳ͸ ͳȋ͹ǤͳΨȌ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    †‹ˆˆ‡”‡–‹ƒ–‡† ȋʹͷǤͲΨȌ
    ‘‘”Ž› ͳʹȋͳͶǤͺΨȌ ͳͳȋͳͶǤͳΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͺȋͳʹǤͷΨȌ ͵ȋʹͳǤͶΨȌ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    †‹ˆˆ‡”‡–‹ƒ–‡†
    ‡ŽŽ ͷȋ͸ǤʹΨȌ ͷȋ͸ǤͶΨȌ Ͳ ͷȋ͹ǤͺΨȌ Ͳ Ǧ Ͳ
    †‹ˆˆ‡”‡–‹ƒ–‡†
    –Š‡” Ͷ͸ȋͷ͸ǤͺΨȌ Ͷͷȋͷ͹Ǥ͹ΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͵ͷ ͳͲ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͷͶǤ͹ΨȌ ȋ͹ͳǤͶΨȌ
    ‘–”‡’‘”–‡† Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ

    ͷͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    p Value
    gAS vs
    CHRYSALIS FAS gAS gNT gCEAS gAS- gAS-F gAS-Unk gAS-Unk
    ƒ ‡”•–ƒ‰‡ƒ–‹‹–‹ƒŽ
    †‹ƒ‰‘•‹•
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͲ͹ͺ
    Ͳ Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
     ͸ȋ͹ǤͶΨȌ ͸ȋ͹Ǥ͹ΨȌ Ͳ Ͷȋ͸Ǥ͵ΨȌ ʹȋͳͶǤ͵ΨȌ Ǧ Ͳ
     ͳȋͳǤʹΨȌ ͳȋͳǤ͵ΨȌ Ͳ ͳȋͳǤ͸ΨȌ Ͳ Ǧ Ͳ
     ͳȋͳǤʹΨȌ ͳȋͳǤ͵ΨȌ Ͳ ͳȋͳǤ͸ΨȌ Ͳ Ǧ Ͳ
     ͶȋͶǤͻΨȌ ͵ȋ͵ǤͺΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͵ȋͶǤ͹ΨȌ Ͳ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
     ͶȋͶǤͻΨȌ ͵ȋ͵ǤͺΨȌ ͳȋ͵͵Ǥ͵ΨȌ ʹȋ͵ǤͳΨȌ ͳȋ͹ǤͳΨȌ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
     ͶȋͶǤͻΨȌ ͶȋͷǤͳΨȌ Ͳ ͵ȋͶǤ͹ΨȌ ͳȋ͹ǤͳΨȌ Ǧ Ͳ
     ͸ͳȋ͹ͷǤ͵ΨȌ ͸Ͳȋ͹͸ǤͻΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͷͲ ͳͲ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋ͹ͺǤͳΨȌ ȋ͹ͳǤͶΨȌ
    ‘–”‡’‘”–‡† Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
    ‘ ƒ–‹‘‘ˆ
    ‡–ƒ•–ƒ•‹•ƒ
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͷͻͺ
    ‘‡ ͵ͶȋͶʹǤͲΨȌ ͵͵ȋͶʹǤ͵ΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͵Ͳ ͵ȋʹͳǤͶΨȌ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͶ͸ǤͻΨȌ
    ‹˜‡” ͹ȋͺǤ͸ΨȌ ͹ȋͻǤͲΨȌ Ͳ ͷȋ͹ǤͺΨȌ ʹȋͳͶǤ͵ΨȌ Ǧ Ͳ
    ”ƒ‹ ͳͺȋʹʹǤʹΨȌ ͳ͹ȋʹͳǤͺΨȌ ͳȋ͵͵Ǥ͵ΨȌ ͳͷ ʹȋͳͶǤ͵ΨȌ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋʹ͵ǤͶΨȌ
    ›’Š‘†‡ Ͷ͵ȋͷ͵ǤͳΨȌ Ͷ͵ȋͷͷǤͳΨȌ Ͳ ͵ͻ ͶȋʹͺǤ͸ΨȌ Ǧ Ͳ
    ȋ͸ͲǤͻΨȌ
    †”‡ƒŽ Žƒ† ͵ȋ͵Ǥ͹ΨȌ ͵ȋ͵ǤͺΨȌ Ͳ ͵ȋͶǤ͹ΨȌ Ͳ Ǧ Ͳ
    –Š‡” ͶͷȋͷͷǤ͸ΨȌ Ͷʹȋͷ͵ǤͺΨȌ ͵ ͵ͳ ͳͳ Ǧ ͵
    ȋͳͲͲǤͲΨȌ ȋͶͺǤͶΨȌ ȋ͹ͺǤ͸ΨȌ ȋͳͲͲǤͲΨȌ
    ‘–”‡’‘”–‡† Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
    ‹‡ˆ”‘‹‹–‹ƒŽ
    †‹ƒ‰‘•‹•‘ˆ ƒ ‡”–‘
    ˆ‹”•–†‘•‡ȋ‘–Š•Ȍ
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͺͺͳ
    ‡ƒȋȌ ʹʹǤͻͲͷ ʹʹǤͺ͵ͷ ʹͶǤ͹ͳ͹ ʹ͵Ǥ͸͸ͺ ͳͻǤͲʹͷ Ǧ ʹͶǤ͹ͳ͹
    ȋʹͳǤͳͻͲͳȌ ȋʹͳǤ͵ͺʹͺȌ ȋͳͺǤ͹͹͹͵Ȍ ȋʹʹǤ͸ʹͻͷȌ ȋͳͶǤͶͲʹͲȌ ȋͳͺǤ͹͹͹͵Ȍ
    ‡†‹ƒ ͳ͹ǤͲͳͺ ͳ͸Ǥͻͺ͸ ʹ͸ǤͲʹͳ ͳ͸Ǥ͹ͺͻ ͳͺǤͶ͵ͳ Ǧ ʹ͸ǤͲʹͳ
    ƒ‰‡ ȋͳǤͶͷǢ ȋͳǤͶͷǢ ȋͷǤ͵ʹǢ ȋʹǤͺ͸Ǣ ȋͳǤͶͷǢ Ǧ ȋͷǤ͵ʹǢ
    ͳ͵ͲǤͳͲȌ ͳ͵ͲǤͳͲȌ ͶʹǤͺͳȌ ͳ͵ͲǤͳͲȌ ͶͷǤ͵͹Ȍ ͶʹǤͺͳȌ
    ‹‡ˆ”‘‡–ƒ•–ƒ–‹ 
    †‹•‡ƒ•‡†‹ƒ‰‘•‹•–‘
    ˆ‹”•–†‘•‡ȋ‘–Š•Ȍ
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͶͲͳ
    ‡ƒȋȌ ͳͺǤͲ͹ͳ ͳͺǤ͵͹Ͷ ͳͲǤͳͺͷ ͳͺǤ͹Ͷͳ ͳ͸Ǥ͸ͻͷ Ǧ ͳͲǤͳͺͷ
    ȋͳ͸ǤͶͶʹͶȌ ȋͳ͸Ǥ͸͸Ͷ͹Ȍ ȋͷǤͲ͵Ͷ͹Ȍ ȋͳ͹ǤʹͷʹͶȌ ȋͳͶǤͲͻͺͶȌ ȋͷǤͲ͵Ͷ͹Ȍ
    ‡†‹ƒ ͳͶǤͳ͸Ͳ ͳͶǤͺͺ͵ ͻǤͺͷ͸ ͳͶǤͺͺ͵ ͳͶǤͺͷͲ Ǧ ͻǤͺͷ͸
    ƒ‰‡ ȋͲǤ͸ͻǢ ȋͲǤ͸ͻǢ ȋͷǤ͵ʹǢ ȋͲǤ͸ͻǢ ȋͳǤ͵ͷǢ Ǧ ȋͷǤ͵ʹǢ
    ͳͳ͸ǤͶͲȌ ͳͳ͸ǤͶͲȌ ͳͷǤ͵ͺȌ ͳͳ͸ǤͶͲȌ ͶͷǤ͵͹Ȍ ͳͷǤ͵ͺȌ
    —„‡”‘ˆ’”‹‘”Ž‹‡•
    ‘ˆ–Š‡”ƒ’›
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤ͸ͳͶ
    ‡ƒȋȌ ʹǤ͵ȋͳǤͶͳȌ ʹǤʹȋͳǤͶͲȌ ʹǤ͹ȋʹǤͲͺȌ ʹǤ͵ȋͳǤͶͷȌ ʹǤͲȋͳǤͳͳȌ Ǧ ʹǤ͹ȋʹǤͲͺȌ
    ‡†‹ƒ ʹǤͲ ʹǤͲ ʹǤͲ ʹǤͲ ʹǤͲ Ǧ ʹǤͲ
    ƒ‰‡ ȋͳǢ͹Ȍ ȋͳǢ͹Ȍ ȋͳǢͷȌ ȋͳǢ͹Ȍ ȋͳǢͶȌ Ǧ ȋͳǢͷȌ

    ͸Ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    p Value
    gAS vs
    CHRYSALIS FAS gAS gNT gCEAS gAS- gAS-F gAS-Unk gAS-Unk
     ’‡”ˆ‘”ƒ ‡
    •–ƒ–—•
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤͻͺͲ
    Ͳ ʹ͸ȋ͵ʹǤͳΨȌ ʹͷȋ͵ʹǤͳΨȌ ͳȋ͵͵Ǥ͵ΨȌ ʹͲ ͷȋ͵ͷǤ͹ΨȌ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋ͵ͳǤ͵ΨȌ
    ͳ ͷͶȋ͸͸Ǥ͹ΨȌ ͷʹȋ͸͸Ǥ͹ΨȌ ʹȋ͸͸Ǥ͹ΨȌ Ͷ͵ ͻȋ͸ͶǤ͵ΨȌ Ǧ ʹȋ͸͸Ǥ͹ΨȌ
    ȋ͸͹ǤʹΨȌ
    ʹ ͳȋͳǤʹΨȌ ͳȋͳǤ͵ΨȌ Ͳ ͳȋͳǤ͸ΨȌ Ͳ Ǧ Ͳ
    εʹ Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
    ‘–”‡’‘”–‡† Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
    ‹•–‘”›‘ˆ•‘‹‰
     ͺͳ ͹ͺ ͵ ͸Ͷ ͳͶ Ͳ ͵ ͲǤ͸͵ͳ
    ‡• ͵ͺȋͶ͸ǤͻΨȌ ͵͹ȋͶ͹ǤͶΨȌ ͳȋ͵͵Ǥ͵ΨȌ ʹ͹ ͳͲ Ǧ ͳȋ͵͵Ǥ͵ΨȌ
    ȋͶʹǤʹΨȌ ȋ͹ͳǤͶΨȌ
    ‘ Ͷ͵ȋͷ͵ǤͳΨȌ ͶͳȋͷʹǤ͸ΨȌ ʹȋ͸͸Ǥ͹ΨȌ ͵͹ ͶȋʹͺǤ͸ΨȌ Ǧ ʹȋ͸͸Ǥ͹ΨȌ
    ȋͷ͹ǤͺΨȌ
    ‘™ Ͳ Ͳ Ͳ Ͳ Ͳ Ǧ Ͳ
     ǡƒ•–‡”‘‘’‡”ƒ–‹˜‡ ‘Ž‘‰› ”‘—’Ǥƒ—„Œ‡ –• ƒ„‡ ‘—–‡†‹‘”‡–Šƒ‘‡ ƒ–‡‰‘”›Ǥ
    ǣ —ŽŽƒŽ›•‹•‡–ǡ‰ǣ —ƒ”†ƒ–͵͸ͲšƒƒŽ›•‹••‡–ǡ‰ǣ —ƒ”†ƒ–͵͸Ͳš‘––‡•–‡†•‡–ǡ
    ‰ǣ —ƒ”†ƒ–͵͸Ͳš’”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›ƒƒŽ›•‹••‡–ǡ‰ǣ —ƒ”†ƒ–͵͸ͲšƒƒŽ›•‹••‡–ǡ
    ‰Ǧ ǣ —ƒ”†ƒ–͵͸ͲšƒƒŽ›•‹••‡–ˆƒ‹Ž‡†ǡ‰Ǧǣ —ƒ”†ƒ–͵͸Ͳš—‘™•‡–

    ‡•‹–‹˜‹–›ƒŽ›•‹•”‡˜ƒŽ‡ ‡—„Ǧ–—†›‘’—Žƒ–‹‘‡’”‡•‡–ƒ–‹˜‡‡••‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡


    Ž‹‹ ƒŽŠƒ”ƒ –‡”‹•–‹ •
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ  • ”‡‡ˆƒ‹Ž•—„Œ‡ –•ƒ† •–—†›
    •—„Œ‡ –•‹ Ž—†‡†‹–Š‡ —ƒ”†ƒ–͵͸ͲšΪŽ‘ ƒŽ–‡•–Ȃ•‡•‹–‹˜‹–›ƒƒŽ›•‹•ƒ”‡”‡’‘”–‡†‹Table 46
    ƒ†Table 47ƒŽ‘‰•‹†‡–Š‘•‡ˆ‘”–Š‡’”‹ƒ”›ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ȋ ȌǤ
    ”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›ȋǦǡǦƒ†ǦȌ•—„Œ‡ –•™‡”‡•‹‹Žƒ”–‘–Š‡ ™‹–Š”‡‰ƒ”†•–‘
    †‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •Ǥ

    Table 46. Demographics of the Prevalence Sub-Study Subjects and the FAS
    CHRYSALIS FAS AAAS-L AAAS-C AAAS-P
    ƒŽ›•‹••‡–ǣ ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‰‡ǡ›‡ƒ”•
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‡ƒȋȌ ͸ʹǤ͵ȋͻǤͻ͸Ȍ ͸ʹǤʹȋͻǤͻͻȌ ͷͺǤ͹ȋͳͳǤͲ͸Ȍ ͸͹ǤͶȋͻǤ͸Ȍ
    ‡†‹ƒ ͸ʹǤͲ ͸ʹǤͲ ͷͻǤͲ ͸͸Ǥͷ
    ƒ‰‡ ȋͶʹǢͺͶȌ ȋͶͳǢͺͶȌ ȋ͵ͶǢͺ͵Ȍ ͶͳǦͻͳ
    δ͸ͷ ͶͺȋͷͻǤ͵ΨȌ ͷ͸ȋͷ͹Ǥ͹ΨȌ ͷͷȋ͸͸Ǥ͵ΨȌ ͶͳȋͶ͸ǤͷͻΨȌ
    εα͸ͷ ͵͵ȋͶͲǤ͹ΨȌ ͶͳȋͶʹǤ͵ΨȌ ʹͺȋ͵͵Ǥ͹ΨȌ Ͷ͹ȋͷ͵ǤͶͳΨȌ
    δ͹ͷ ͹ͶȋͻͳǤͶΨȌ ͺͻȋͻͳǤͺΨȌ ͹ͷȋͻͲǤͶΨȌ ͸ͻȋ͹ͺǤͶͳΨȌ
    εα͹ͷ ͹ȋͺǤ͸ΨȌ ͺȋͺǤʹΨȌ ͺȋͻǤ͸ΨȌ ͳͻȋʹͳǤͷͻΨȌ
    ‡š
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‡ƒŽ‡ ͶͺȋͷͻǤ͵ΨȌ ͸Ͳȋ͸ͳǤͻΨȌ ͷʹȋ͸ʹǤ͹ΨȌ ͷ͵ȋ͸ͲǤʹ͵ΨȌ
    ƒŽ‡ ͵͵ȋͶͲǤ͹ΨȌ ͵͹ȋ͵ͺǤͳΨȌ ͵ͳȋ͵͹Ǥ͵ΨȌ ͵ͷȋ͵ͻǤ͹͹ΨȌ

    ͸ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    CHRYSALIS FAS AAAS-L AAAS-C AAAS-P
    ƒ ‡
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‡”‹ ƒ †‹ƒ‘”Žƒ•ƒ Ͳ Ͳ Ͳ Ͳ
    ƒ–‹˜‡
    •‹ƒ ͶͲȋͶͻǤͶΨȌ ͶͺȋͶͻǤͷΨȌ Ͷ͹ȋͷ͸Ǥ͸ΨȌ ͷȋͷǤ͸ͺΨȌ
    Žƒ ‘”ˆ”‹ ƒ‡”‹ ƒ ʹȋʹǤͷΨȌ ͳȋͳǤͲΨȌ Ͳ ͹ȋ͹ǤͻͷΨȌ
    ƒ–‹˜‡ ƒ™ƒ‹‹ƒ‘”‘–Š‡”ƒ ‹ˆ‹  Ͳ Ͳ Ͳ Ͳ
    •Žƒ†‡”
    Š‹–‡ ͵Ͳȋ͵͹ǤͲΨȌ ͵ͺȋ͵ͻǤʹΨȌ ʹͻȋ͵ͶǤͻΨȌ ͹͵ȋͺʹǤͻͷΨȌ
    —Ž–‹’Ž‡ Ͳ Ͳ Ͳ
    ‘–”‡’‘”–‡† ͻȋͳͳǤͳΨȌ ͳͲȋͳͲǤ͵ΨȌ ͹ȋͺǤͶΨȌ ͵ȋ͵ǤͶͳΨȌ
    –Š‹ ‹–›
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‹•’ƒ‹ ‘”ƒ–‹‘ ͵ȋ͵Ǥ͹ΨȌ ͶȋͶǤͳΨȌ ʹȋʹǤͶΨȌ ͳͲȋͳͳǤ͵͸ΨȌ
    ‘– ‹•’ƒ‹ ‘”ƒ–‹‘ ͸ͺȋͺͶǤͲΨȌ ͺʹȋͺͶǤͷΨȌ ͹ʹȋͺ͸Ǥ͹ΨȌ ͹ͺȋͺͺǤ͸ͶΨȌ
    ‘–”‡’‘”–‡† ͳͲȋͳʹǤ͵ΨȌ ͳͳȋͳͳǤ͵ΨȌ ͻȋͳͲǤͺΨȌ Ͳ
    ‡‹‰Š–ǡ‰
     ͺͳ ͻ͹ Ͳ Ȁ
    ‡ƒȋȌ ͸͹ǤͶͻȋͳ͸Ǥ͹ͺͶȌ ͸ͷǤͳ͹ȋͳͷǤͺ͸ʹȌ Ǧ Ȁ
    ‡†‹ƒ ͸ʹǤͷͲ ͸ʹǤͳ Ǧ Ȁ
    ƒ‰‡ ȋ͵ͷǤͶǢͳͳͷǤͲȌ ȋ͵ͷǤͶǢͳͳͷǤͲȌ Ǧ Ȁ
    ‡‹‰Š–ǡ 
     ͺͳ ͻ͹ Ͳ Ȁ
    ‡ƒȋȌ ͳ͸͵Ǥ͹ͳȋͻǤͲʹͲȌ ͳ͸͵ǤͶ͹ȋͺǤ͹ʹͻȌ Ǧ Ȁ
    ‡†‹ƒ ͳ͸ʹǤ͸Ͳ ͳ͸͵ǤͲ Ǧ Ȁ
    ƒ‰‡ ȋͳͶͶǤͷǢͳͻʹǤͲȌ ȋͳͶͶǤͷǢͳͻʹǤͲȌ Ǧ Ȁ
    ‘†›ƒ••‹†‡šǡ‰Ȁʹ
     ͺͳ ͻ͹ Ͳ Ȁ
    ‡ƒȋȌ ʹͶǤͻͻ͵ȋͶǤͻͲͶ͹Ȍ ʹͶǤʹ͵ͳȋͶǤ͹ʹͲ͸Ȍ Ǧ Ȁ
    ‡†‹ƒ ʹͶǤʹͷͲ ʹ͵ǤͻͶ͸ Ǧ Ȁ
    ƒ‰‡ ȋͳͶǤͲͲǢ͵͸Ǥͺ͹Ȍ ȋͳͶǤͲͲǢ͵͸Ǥͺ͹Ȍ Ǧ Ȁ
    †‡”™‡‹‰Š–δͳͺǤͷ ͶȋͶǤͻΨȌ ͺȋͺǤʹΨȌ Ǧ Ȁ
    ‘”ƒŽͳͺǤͷǦδʹͷ Ͷ͵ȋͷ͵ǤͳΨȌ ͷͷȋͷ͸Ǥ͹ΨȌ Ǧ Ȁ
    ˜‡”™‡‹‰Š–ʹͷǦδ͵Ͳ ʹͳȋʹͷǤͻΨȌ ʹʹȋʹʹǤ͹ΨȌ Ǧ Ȁ
    „‡•‡εα͵Ͳ ͳ͵ȋͳ͸ǤͲΨȌ ͳʹȋͳʹǤͶΨȌ Ǧ Ȁ
    ‘ ƒŽ‡•–›’‡ȗ
     ͺͳ ͻ͹ ͺ͵ ͺͺ
     ȋŽ‘‘†Ȍ ͶȋͶǤͻΨȌ ͸ȋ͸ǤʹΨȌ Ͳ
     ȋ‹••—‡Ȍ ͵ͶȋͶʹǤͲΨȌ ͵͹ȋ͵ͺǤͳΨȌ ͳȋͳǤʹΨȌ
     ȋŽ‘‘†Ȍ ͳȋͳǤʹΨȌ ʹȋʹǤͳΨȌ Ͳ
     ȋ‹••—‡Ȍ ͹ȋͺǤ͸ΨȌ ͳͲȋͳͲǤ͵ΨȌ Ͳ
    ȋŽ‘‘†Ȍ ͳȋͳǤʹΨȌ ͳȋͳǤͲΨȌ Ͳ
    ȋ‹••—‡Ȍ ͵Ͳȋ͵͹ǤͲΨȌ ͵͸ȋ͵͹ǤͳΨȌ ʹȋʹǤͶΨȌ ͺͺ
    ȋ‹••—‡Ȍ ͶȋͶǤͻΨȌ ͶȋͶǤͳΨȌ ͳȋͳǤʹΨȌ
    ȋ‘™Ȍ Ͳ ͳȋͳǤͲΨȌ ͹ͻȋͻͷǤʹΨȌ
    ȀǦ‘–ƒ˜ƒ‹Žƒ„Ž‡Ǥȗ‘ ƒŽ–‡•––›’‡ƒ•†‡ˆ‹‡†„›–Š‡‡”‘ŽŽ‹‰•‹–‡Ǥ
    ǣ —ŽŽƒŽ›•‹•‡–ǡǦǣ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–Ȃ‘ ƒŽ–‡•–‹‰ǡ
    Ǧǣ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–Ȃ‡–”ƒŽ –‹••—‡–‡•–‹‰ǡ
    Ǧǣ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–Ȃ–‡•–‹‰

    ͸ʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 47. Baseline Clinical Characteristics of the Prevalence Sub-Study Subjects and the FAS
    CHRYSALIS FAS AAAS L AAAS C AAAS P
    ƒŽ›•‹••‡–ǣ ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‹–‹ƒŽ†‹ƒ‰‘•‹•
    •—„–›’‡
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    †‡‘ ƒ” ‹‘ƒ ͹͹ȋͻͷǤͳΨȌ ͻʹȋͻͶǤͺΨȌ Ͳ ͺͶȋͻͷǤͶͷΨȌ
    ƒ”‰‡ ‡ŽŽ ƒ” ‹‘ƒ Ͳ Ͳ Ͳ ͵ȋ͵ǤͶͳΨȌ
    “—ƒ‘—• ‡ŽŽ ƒ” ‹‘ƒ ͵ȋ͵Ǥ͹ΨȌ ͵ȋ͵ǤͳΨȌ Ͳ Ȁ
    –Š‡” ͳȋͳǤʹΨȌ ʹȋʹǤͳΨȌ Ͳ ͳȋͳǤͳͶΨȌ
    ‘–”‡’‘”–‡† Ͳ Ͳ ͺ͵ȋͳͲͲǤͲΨȌ Ͳ
    ‹•–‘Ž‘‰›‰”ƒ†‡ƒ–‹‹–‹ƒŽ
    †‹ƒ‰‘•‹•
     ͺͳ ͻ͹ ͺ͵ Ȁ
    ‘†‡”ƒ–‡Ž›†‹ˆˆ‡”‡–‹ƒ–‡† ͳͺȋʹʹǤʹΨȌ ʹͳȋʹͳǤ͸ΨȌ Ͳ Ȁ
    ‘‘”Ž›†‹ˆˆ‡”‡–‹ƒ–‡† ͳʹȋͳͶǤͺΨȌ ͳ͹ȋͳ͹ǤͷΨȌ Ͳ Ȁ
    ‡ŽŽ†‹ˆˆ‡”‡–‹ƒ–‡† ͷȋ͸ǤʹΨȌ ͸ȋ͸ǤʹΨȌ Ͳ Ȁ
    –Š‡” Ͷ͸ȋͷ͸ǤͺΨȌ ͷ͵ȋͷͶǤ͸ΨȌ Ͳ Ȁ
    ‘–”‡’‘”–‡† Ͳ Ͳ ͺ͵ȋͳͲͲǤͲΨȌ Ȁ
    ƒ ‡”•–ƒ‰‡ƒ–‹‹–‹ƒŽ
    †‹ƒ‰‘•‹•
     ͺͳ ͻ͹ Ͳ ͺͺ
    Ͳ Ͳ Ͳ Ǧ Ͳ
     ͸ȋ͹ǤͶΨȌ ͸ȋ͸ǤʹΨȌ Ǧ ͶȋͶǤͷͷΨȌ
     ͳȋͳǤʹΨȌ ͳȋͳǤͲΨȌ Ǧ Ͳ
     ͳȋͳǤʹΨȌ ʹȋʹǤͳΨȌ Ǧ ͵ȋ͵ǤͶͳΨȌ
     ͶȋͶǤͻΨȌ ͵ȋ͵ǤͳΨȌ Ǧ Ͳ
     ͶȋͶǤͻΨȌ ͶȋͶǤͳΨȌ Ǧ ͸ȋ͸ǤͺʹΨȌ
     ͶȋͶǤͻΨȌ ͶȋͶǤͳΨȌ Ǧ ͵ȋ͵ǤͶͳΨȌ
     ͸ͳȋ͹ͷǤ͵ΨȌ ͹͹ȋ͹ͻǤͶΨȌ Ǧ ͹ʹȋͺͳǤͺʹΨȌ
    ‘–”‡’‘”–‡† Ͳ Ͳ Ǧ Ͳ
    ‘ ƒ–‹‘‘ˆ‡–ƒ•–ƒ•‹•
     ͺͳ ͻ͹ ͺ͵ Ȁ
    ‘‡ ͵ͶȋͶʹǤͲΨȌ ͶͶȋͶͷǤͶΨȌ Ͳ Ȁ
    ‹˜‡” ͹ȋͺǤ͸ΨȌ ͳʹȋͳʹǤͶΨȌ Ͳ Ȁ
    ”ƒ‹ ͳͺȋʹʹǤʹΨȌ ʹͶȋʹͶǤ͹ΨȌ Ͳ Ȁ
    ›’Š‘†‡ Ͷ͵ȋͷ͵ǤͳΨȌ ͷͷȋͷ͸Ǥ͹ΨȌ Ͳ Ȁ
    †”‡ƒŽ Žƒ† ͵ȋ͵Ǥ͹ΨȌ ͷȋͷǤʹΨȌ Ͳ Ȁ
    –Š‡” ͶͷȋͷͷǤ͸ΨȌ ͷʹȋͷ͵Ǥ͸ΨȌ Ͳ Ȁ
    ‘–”‡’‘”–‡† Ͳ Ͳ ͺ͵ȋͳͲͲǤͲΨȌ Ȁ
    ‹‡ˆ”‘‹‹–‹ƒŽ†‹ƒ‰‘•‹•‘ˆ
    ƒ ‡”–‘ˆ‹”•–†‘•‡ȋ‘–Š•Ȍ
     ͺͳ ͻ͹ Ͳ Ȁ
    ‡ƒȋȌ ʹʹǤͻͲͷȋʹͳǤͳͻͲͳȌ ʹʹǤͲͷͳȋʹͲǤ͹ͷʹͲȌ Ǧ Ȁ
    ‡†‹ƒ ͳ͹ǤͲͳͺ ͳ͸Ǥ͸ʹͶ Ǧ Ȁ
    ƒ‰‡ ȋͳǤͶͷǢͳ͵ͲǤͳͲȌ ȋͳǤͶͷǢͳ͵ͲǤͳͲȌ Ǧ Ȁ
    Ȁ

    ͸͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    CHRYSALIS FAS AAAS L AAAS C AAAS P
    ‹‡ˆ”‘‡–ƒ•–ƒ–‹ †‹•‡ƒ•‡
    †‹ƒ‰‘•‹•–‘ˆ‹”•–†‘•‡
    ȋ‘–Š•Ȍ
     ͺͳ ͻ͹ Ͳ Ȁ
    ‡ƒȋȌ ͳͺǤͲ͹ͳȋͳ͸ǤͶͶʹͶȌ ͳ͹Ǥͺ͹ͲȋͳͷǤ͹ͲͶͶȌ Ǧ Ȁ
    ‡†‹ƒ ͳͶǤͳ͸Ͳ ͳͶǤͶͺͻ Ǧ Ȁ
    ƒ‰‡ ȋͲǤ͸ͻǢͳͳ͸ǤͶͲȌ ȋͲǤ͸ͻǢͳͳ͸ǤͶͲȌ Ǧ Ȁ
    —„‡”‘ˆ’”‹‘”Ž‹‡•‘ˆ
    –Š‡”ƒ’›
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‡ƒȋȌ ʹǤ͵ȋͳǤͶͳȌ ʹǤͳȋͳǤ͵ͶȌ ʹǤͺȋͳǤͷʹȌ Ͳ
    ‡†‹ƒ ʹǤͲ ʹǤͲ ʹǤͲ Ͳ
    ƒ‰‡ ȋͳǢ͹Ȍ ȋͳǢ͹Ȍ ȋͲǢ͹Ȍ ȋͲǢͲȌ
     ’‡”ˆ‘”ƒ ‡•–ƒ–—•
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    Ͳ ʹ͸ȋ͵ʹǤͳΨȌ ʹ͹ȋʹ͹ǤͺΨȌ Ͳ ͳͻȋʹͳǤͷͻΨȌ
    ͳ ͷͶȋ͸͸Ǥ͹ΨȌ ͸ͻȋ͹ͳǤͳΨȌ Ͳ ͷͻȋ͸͹ǤͲͷΨȌ
    ʹ ͳȋͳǤʹΨȌ ͳȋͳǤͲΨȌ Ͳ ͹ȋ͹ǤͻͷΨȌ
    εʹ Ͳ Ͳ Ͳ ͳȋͳǤͳͶΨȌ
    ‘–”‡’‘”–‡† Ͳ Ͳ ͺ͵ȋͳͲͲǤͲΨȌ ʹȋʹǤʹ͹ΨȌ
    ‹•–‘”›‘ˆ•‘‹‰
     ͺͳ ͻ͹ ͺ͵ ͺͺ
    ‡• ͵ͺȋͶ͸ǤͻΨȌ ͶʹȋͶ͵Ǥ͵ΨȌ ͳͻȋʹʹǤͻΨȌ ͸͸ȋ͹ͷǤͲͲΨȌ
    ‘ Ͷ͵ȋͷ͵ǤͳΨȌ ͷͷȋͷ͸Ǥ͹ΨȌ ͶͷȋͷͶǤʹΨȌ ͳͻȋʹͳǤͷͻΨȌ
    ‘™ Ͳ Ͳ ͳͻȋʹʹǤͻΨȌ ͵ȋ͵ǤͶͳΨȌ
    Ȁǡ‘–ƒ˜ƒ‹Žƒ„Ž‡Ǥƒ—„Œ‡ –• ƒ„‡ ‘—–‡†‹‘”‡–Šƒ‘‡ ƒ–‡‰‘”›Ǥ
    ǣ —ŽŽƒŽ›•‹•‡–ǡǦǣ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–Ȃ‘ ƒŽ–‡•–‹‰ǡ
    Ǧǣ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–Ȃ‡–”ƒŽ –‹••—‡–‡•–‹‰ǡ
    Ǧǣ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–Ȃ–‡•–‹‰

    ‹ƒ‰‘•–‹ –—†›”‹ƒ”›„Œ‡ –‹˜‡ƒŽ›•‹•‡•—Ž–•


    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡™ƒ•ƒ••‡••‡†„› ‘’ƒ”‹‰–Š‡‡ˆˆ‹ ƒ ›‘ˆ•‹‰Ž‡Ǧƒ‰‡–ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™‹
    •—„Œ‡ –•’‘•‹–‹˜‡ˆ‘”EGFR‡š‘ʹͲ‹•‡”–‹‘•„› —ƒ”†ƒ–͵͸Ͳš–‘–Š‡„‡ Šƒ”‡ˆˆ‹ ƒ › ‹–‡†‹
    –Š‡  •–—†›ƒ†‘†‡Ž‹‰–Š‡‹’ƒ –‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡Ž‘ ƒŽ–‡•–Ǧ‡‰ƒ–‹˜‡
    ’‘’—Žƒ–‹‘ƒ†•—„Œ‡ –•™‹–Š‘—– —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•Ǥ
    ƒˆ‡–›‡•—Ž–•
    ƒ–ƒ”‡‰ƒ”†‹‰–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‹ ƒ ›‘ˆƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™–Š‡”ƒ’›ƒ”‡’”‡•‡–‡†‹–Š‡‘”‹‰‹ƒŽ
    †”—‰ƒ’’”‘˜ƒŽƒ†ƒ”‡•—ƒ”‹œ‡†‹–Š‡†”—‰Žƒ„‡ŽǤ‡ˆ‡”–‘–Š‡ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™Žƒ„‡Žˆ‘”‘”‡
    ‹ˆ‘”ƒ–‹‘Ǥ‘ƒ†˜‡”•‡‡˜‡–•™‡”‡”‡’‘”–‡†‹–Š‡ ‘†— –‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†‹‡•ƒ•–Š‡•‡
    ‹˜‘Ž˜‡†”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ„ƒ‡†•’‡ ‹‡•‘Ž›Ǥ
    ”‹ƒ”›ˆˆ‹ ƒ ›‡•—Ž–•
    Š‡‘„•‡”˜‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹••‡–ȋ‰Ȍ‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†›„›„Ž‹†‡†
    ‹†‡’‡†‡– ‡–”ƒŽ”‡˜‹‡™™ƒ•͵ͻǤͳΨȋͻͷΨ ʹ͹ǤͳΨȂͷʹǤͳΨǡTable 48ȌǤŠ‡Ž‘™‡”Ž‹‹–‘ˆ–Š‡
    ͻͷΨ ‘ˆʹ͹ǤͳΨ‡•–ƒ„Ž‹•Š‡••–ƒ–‹•–‹ ƒŽŽ›•‹‰‹ˆ‹ ƒ–ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™‡ˆˆ‹ ƒ ›”‡Žƒ–‹˜‡–‘–Š‡•‹œ‡Ǧ
    ƒ†Œ—•–‡†„‡ Šƒ”‘ˆͳͶΨȋ—ƒ†Œ—•–‡†„‡ Šƒ”ͳͷΨȌˆ”‘–Š‡   Ž‹‹ ƒŽ•–—†›‹
    –Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡŽ‘ ƒŽ–‡•–Ǧ’‘•‹–‹˜‡’‘”–‹‘‘ˆ–Š‡‹–‡†‡†—•‡’‘’—Žƒ–‹‘ƒ†•ƒ–‹•ˆ‹‡•

    ͸Ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    –Š‡’”‡•’‡ ‹ˆ‹‡†‡ˆˆ‹ ƒ ›ƒ ‡’–ƒ ‡ ”‹–‡”‹‘ǤŠ‡‰’‘‹–‡•–‹ƒ–‡™ƒ•ƒŽ•‘•‹‹Žƒ”–‘–Š‡
    ‘ˆ͵ͻǤͷΨȋͻͷΨ ʹͺǤͺΨȂͷͳǤͲΨǡTable 48 Ǥ

    Table 48. Summary of ORR in the gCEAS and FAS by BICR


       gCEAS FAS
    Analysis set: Efficacy 64 81
    ‡•–‘˜‡”ƒŽŽ”‡•’‘•‡  
     ͸Ͷ ͺͳ
    ‘’Ž‡–‡”‡•’‘•‡ȋȌ ʹȋ͵ǤͳΨȌ ͵ȋ͵Ǥ͹ΨȌ
    ƒ”–‹ƒŽ”‡•’‘•‡ȋ  ʹ͵ȋ͵ͷǤͻΨȌ ʹͻȋ͵ͷǤͺΨȌ
    –ƒ„Ž‡†‹•‡ƒ•‡ȋ  ͵ͲȋͶ͸ǤͻΨȌ ͵ͻȋͶͺǤͳΨȌ
    ”‘‰”‡••‹˜‡†‹•‡ƒ•‡ȋȌ ͹ȋͳͲǤͻΨȌ ͺȋͻǤͻΨȌ
    ‘–‡˜ƒŽ—ƒ„Ž‡Ȁ—‘™ ʹȋ͵ǤͳΨȌ ʹȋʹǤͷΨȌ
    ˜‡”ƒŽŽ”‡•’‘•‡”ƒ–‡ȋ‘ˆ‹”‡†Ϊ‘ˆ‹”‡†Ȍ ʹͷȋ͵ͻǤͳΨȌ ͵ʹȋ͵ͻǤͷΨȌ
    ͻͷΨ  ȋʹ͹ǤͳΨǡͷʹǤͳΨȌ ȋʹͺǤͺΨǡͷͳǤͲΨȌ
    Ž‹‹ ƒŽ„‡‡ˆ‹–”ƒ–‡ƒȋ‘ˆ‹”‡†Ϊ‘ˆ‹”‡†ΪȌ ͶͶȋ͸ͺǤͺΨȌ ͸Ͳȋ͹ͶǤͳΨȌ
    ͻͷΨ  ȋͷͷǤͻΨǡ͹ͻǤͺΨȌ ȋ͸͵ǤͳΨǡͺ͵ǤʹΨȌ

    ‡•‹–‹˜‹–›ƒŽ›•‡•ˆ‘””‹ƒ”›ˆˆ‹ ƒ ›„Œ‡ –‹˜‡ˆ‘”–Š‡”‡’”‡•‡–‡† —ƒ”†ƒ–͵͸Ͳš Ϊ‘ ƒŽ


    –‡•–Ȃƒ–‹‡–‘’—Žƒ–‹‘
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•ƒ„‘˜‡†‡‘•–”ƒ–‡†ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸ͲǦ
    ’‘•‹–‹˜‡ǡŽ‘ ƒŽ–‡•–Ǧ’‘•‹–‹˜‡•—„•‡–‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǤŠ‡•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•™ƒ•†‘‡—•‹‰–Š‡Ž‘™‡”„‘—†‡•–‹ƒ–‡‘ˆ–Š‡ͻͷΨ ˆ‘”–Š‡”ȋŽ‘ ƒŽ–‡•–ΪȁšΪȌǡ™Š‹ Š
    ™ƒ•ͻͷǤ͸ΨǤ‡•‹–‹˜‹–›ƒƒŽ›•‹•‘†‡Ž‹‰‡ˆˆ‹ ƒ ›ƒ ”‘••–Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡
    ’‘’—Žƒ–‹‘—•‹‰ †‡‘•–”ƒ–‡•”‘„—•–‡••–‘–Š‡ ‘–”‹„—–‹‘‘ˆ–Š‡—”‡’”‡•‡–‡†
    —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡŽ‘ ƒŽ–‡•–Ǧ‡‰ƒ–‹˜‡•—„Œ‡ –•ǡ™‹–Š‡•–‹ƒ–‡†•ˆ‘”–Š‡‘˜‡”ƒŽŽ
    —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Š‹‰ŠŽ›•‹‹Žƒ”–‘–Š‘•‡‘„•‡”˜‡†ˆ‘”„‘–Š–Š‡‰ƒ†
    †—‡–‘–Š‡Ž‘™‘„•‡”˜‡†’”‡˜ƒŽ‡ ‡ȋͲΨȌ‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡŽ‘ ƒŽ–‡•–Ǧ‡‰ƒ–‹˜‡
    ’‘’—Žƒ–‹‘Ǥ‘”‡‘˜‡”ǡ–Š‡Ž‘™‡”Ž‹‹–•‘ˆ–Š‡ͻͷΨ ˆ‘”–Š‡‡•–‹ƒ–‡†•ƒ ”‘••ƒŽŽ‘†‡Ž‡†
    ‘†‹–‹‘•‡š ‡‡†‡†–Š‡•‹œ‡Ǧƒ†Œ—•–‡†„‡ Šƒ”‘ˆͳͶΨǡ™Š‹ Š†‡‘•–”ƒ–‡••–ƒ–‹•–‹ ƒŽŽ›Ǧ
    •‹‰‹ˆ‹ ƒ–ƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™‡ˆˆ‹ ƒ ›ƒ ”‘••–Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǡ
    ‹””‡•’‡ –‹˜‡‘ˆƒ‹˜ƒ–ƒƒ„Ǧ˜Œ™‡ˆˆ‹ ƒ ›‹–Š‡‘†‡Ž‡† —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡŽ‘ ƒŽ–‡•–Ǧ
    ‡‰ƒ–‹˜‡•—„Ǧ’‘’—Žƒ–‹‘Ǥ
    ‡ ‘†ƒ”›„Œ‡ –‹˜‡ƒŽ›•‡•
    ‰”‡‡‡–‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†  ”‘ŽŽ‡–‡•–‹‰
    ‰”‡‡‡–„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†’”‡†‘‹ƒ–Ž›–‹••—‡–‡•–‹‰‹–Š‡–‘–ƒŽ
    ’‘’—Žƒ–‹‘ȋ ‘„‹‡†ǦǡǦƒ†ǦȌ‹••Š‘™‹Table 49ǤŠ‡ —ƒ”†ƒ–͵͸Ͳš
    †‹ƒ‰‘•–‹ •–—†›ƒ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹•‘”‹‰‹ƒŽŽ›‹ Ž—†‡†ʹ͸ͺ’ƒ–‹‡–•–‡•–‡†™‹–Š
    —ƒ”†ƒ–͵͸Ͳšƒ†‘–Š‡”–‡•–”‡•—Ž–•ˆ”‘„‘–Š–Š‡  ƒ†  Ž‹‹ ƒŽ•–—†‹‡•ǤŠ‡
    ƒ‰”‡‡‡–ƒƒŽ›•‹••‡–‹ Ž—†‡†ͻ͹’ƒ–‹‡–•™‹–ŠŽ‘ ƒŽ–‡•–”‡•—Ž–•ȋͻ™‹–Š’Žƒ•ƒ–‡•–‹‰”‡•—Ž–•ǡ
    ͺ͹™‹–Š–‹••—‡–‡•–‹‰”‡•—Ž–•ǡͳ™‹–Š–‡•–”‡•—Ž–•—•‹‰ƒ—‘™ƒƒŽ›–‡Ȍǡͺ͵• ”‡‡Ǧˆƒ‹Ž
    ’ƒ–‹‡–•™‹–Š ‡–”ƒŽ–‹••—‡–‡•–”‡•—Ž–•ˆ”‘‘–Š‡” ‘Š‘”–•‘ˆ  ǡƒ†ͺͺ™‹–Š ‘„ƒ• ̺
    EGFR—–ƒ–‹‘–‹••—‡–‡•–”‡•—Ž–•ˆ”‘–Š‡ •–—†›ǤŠ‡ƒ††‹–‹‘ƒŽͳ͸•ƒ’Ž‡•ȋͳ͸Ȁͻ͹Ȍ
    ‹ Ž—†‡†‹–Š‡’‘•‹–‹˜‡ƒ‰”‡‡‡–ƒƒŽ›•‹•Šƒ†–Š‡•ƒ‡‹ Ž—•‹‘ ”‹–‡”‹ƒƒ•–Š‡’”‹ƒ”›
    ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘‡š ‡’––Šƒ––Š‡•‡„‡‰ƒ–”‡ƒ–‡–ƒˆ–‡”–Š‡ Ž‹‹ ƒŽ —–‘ˆˆ†ƒ–‡ƒ†
    –Š‡”‡ˆ‘”‡†‹†‘–Šƒ˜‡͵’‘•–Ǧ„ƒ•‡Ž‹‡†‹•‡ƒ•‡ƒ••‡••‡–ƒ––Š‡ Ž‹‹ ƒŽ —–‘ˆˆǤŠ‡‡‰ƒ–‹˜‡
    ƒ‰”‡‡‡–ƒƒŽ›•‹• ‘Š‘”–†‹†‘–‹ Ž—†‡•ƒ’Ž‡•ˆ”‘–Š‡’”‹ƒ”›”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ǡ„—–
    ͸ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    –Š‡ͺ͵•ƒ’Ž‡•™‡”‡• ”‡‡ˆƒ‹Ž•ˆ”‘‘–Š‡”ƒ”•‘ˆ–Š‡ Ž‹‹ ƒŽ•–—†›ȋ‘ǦEGFR‡š‘ʹͲ
    ‹•‡”–‹‘•ƒ”•‘ˆ  ȌǤˆ–Š‡ͺ͵• ”‡‡Ǧˆƒ‹Ž•ƒ’Ž‡•ƒ†–Š‡ͺͺ•ƒ’Ž‡•ˆ”‘–Š‡ 
    •–—†›ǡͶƒ†͵•ƒ’Ž‡•ǡ”‡•’‡ –‹˜‡Ž›ǡŠƒ†EGFR‡š‘ʹͲ‹•‡”–‹‘—–ƒ–‹‘•‹†‡–‹ˆ‹‡†Ǣƒ†ǡ
    –Š‡”‡ˆ‘”‡‡š Ž—†‡†ˆ”‘–Š‡‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ƒƒŽ›•‹•ǤŠ‡”‡ƒ‹‹‰ͳ͸Ͷ•ƒ’Ž‡•™‡”‡—•‡†
    ˆ‘”‡‰ƒ–‹˜‡ƒ‰”‡‡‡–ƒƒŽ›•‹•ǤŠ‡ˆ‹ƒŽ—„‡”‘ˆ•ƒ’Ž‡•—•‡†‹–Š‡ƒ‰”‡‡‡–ƒƒŽ›•‹•™ƒ•
    ʹ͸ͺǤ
    ‡–”ƒŽ–‡•–‹‰ˆ‘”–Š‡• ”‡‡ˆƒ‹Ž•ƒ’Ž‡•—–‹Ž‹œ‡†–™‘†‹ˆˆ‡”‡––‹••—‡Ǧ„ƒ•‡† –‡•–•ȋ͸ͻΨ™‹–Š
    ‘—†ƒ–‹‘‡̺šƒ†͵ͳΨ™‹–Š ‘‹‡šƒ”‰‡–‡•–Ȍ™Š‹Ž‡•ƒ’Ž‡•ˆ”‘–Š‡ •–—†›
    ™‡”‡•‡Ž‡ –‡†—•‹‰–Š‡–‹••—‡Ǧ„ƒ•‡† ‘„ƒ•̺EGFR—–ƒ–‹‘‡•–Ǥ˜‡”ƒŽŽǡ–Š‡ ‘„‹ƒ–‹‘‘ˆ
    –Š‡  Ž‹‹ ƒŽ•–—†›ƒ†  ‘Ǧ”‡‰‹•–”ƒ–‹‘ ‘Š‘”–• Ž‘•‡Ž›”‡’”‡•‡–•–Š‡Ž‘ ƒŽ
    –‡•–‹‰†‹•–”‹„—–‹‘—•‡†–‘‡”‘ŽŽ–Š‡”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ǡ„‘–Š‹–‡”•‘ˆ‰‡‡”ƒŽ–‡•–
    ‡–Š‘†‘Ž‘‰›ȋi.e.–Š‡”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ͶͲΨǡͷͷΨ Ǣ–Š‡•—’’Ž‡‡–ƒŽ ‘Š‘”–•ͷͳΨ
    ǡͶͻΨ Ȍƒ†•’‡ ‹ˆ‹ –‡•–‡–Š‘†‘Ž‘‰›ȋi.e.–Š‡”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘‡”‘ŽŽ‡†„› 
    ™‹–Š͵ͷؐ ‘‹‡šƒ”‰‡–‡•–ǡ͸ͷΨ ‘—†ƒ–‹‘‡̺šǢ–Š‡•—’’Ž‡‡–ƒŽ ‘Š‘”–•™‹–Š
    ͵ͳΨƒ†͸ͻΨ”‡•’‡ –‹˜‡Ž›ȌǤ —ƒ”†ƒ–͵͸Ͳš†‡‘•–”ƒ–‡•Š‹‰ŠȋͳͲͲΨǡͻͷΨ ͻ͹Ǥ͹ΨȂ
    ͳͲͲΨȌƒ†”‡Žƒ–‹˜‡Ž›Š‹‰Šȋͺ͵Ǥ͹ΨǡͻͷΨ ͹ͷǤͶΨȂͺͻǤͷΨȌ”‡Žƒ–‹˜‡–‘Ž‘ ƒŽ–‡•–‹‰”‡•—Ž–•Ǥ

    Table 49. Unadjusted Agreement Between CHRYSALIS Enrollment Testing, CHRYSALIS Central
    Testing, or cobas EGFR Testing and Guardant360 CDx (AAAS)
    CHRYSALIS Enrollment Testing, CHRYSALIS Central Testing, or
     cobas EGFR Testing
    EGFR exon 20 insertion + EGFR exon 20 insertion - Total
    Guardant360 CDx   
    EGFR‡š‘ʹͲ‹•‡”–‹‘Ϊ ͺ͹ Ͳ ͺ͹
    EGFR‡š‘ʹͲ‹•‡”–‹‘Ǧ ͳ͹ ͳ͸Ͷ ͳͺͳ
    ‘–ƒŽ ͳͲͶ ͳ͸Ͷ ʹ͸ͺ
    ȋͻͷΨ   ͺ͵Ǥ͹Ψȋ͹ͷǤͶΨǦͺͻǤͷΨȌ 
    ȋͻͷΨ Ȍ  ͳͲͲǤͲΨȋͻ͹Ǥ͹ΨǦͳͲͲǤͲΨȌ 
       

    —‡–‘–Š‡‡”‹ Š‡–‘ˆ–Š‡Ǧ’‘’—Žƒ–‹‘ˆ‘”•—„Œ‡ –•’‘•‹–‹˜‡ˆ‘”EGFR‡š‘ʹͲ‹•‡”–‹‘•ǡ


    ƒ†Œ—•–‡†ƒ‰”‡‡‡–™ƒ•ƒ••‡••‡†—•‹‰–Š‡αȋŽ‘ ƒŽ–‡•– Ϊȁ —ƒ”†ƒ–͵͸ͲšΪȌƒ†α
    ȋŽ‘ ƒŽ–‡•–Ȃȁ —ƒ”†ƒ–͵͸ͲšȂȌˆ‘”–Š‡–‘–ƒŽ’‘’—Žƒ–‹‘ȋ ‘„‹‡†ǦǡǦƒ†
    ǦȌǤ –Š‹•ƒƒŽ›•‹•ǡ —ƒ”†ƒ–͵͸Ͳš†‡‘•–”ƒ–‡†Š‹‰Šƒ†Œ—•–‡†‘ˆͳͲͲΨȋͻͷΨ ǡ
    ͻͷǤͺΨǦͳͲͲΨȌƒ†‘ˆͻͻǤ͹ΨȋͻͷΨ ǡͻͻǤ͸ΨǦͻͻǤͺΨȌ”‡Žƒ–‹˜‡–‘Ž‘ ƒŽ–‡•–‹‰ǤŠ‡
    ’”‡˜ƒŽ‡ ‡‡•–‹ƒ–‡ȋŽ‘ ƒŽ–‡•–ΪȌ—•‡†‹–Š‡ƒ†Œ—•–‡†ƒ‰”‡‡‡–™ƒ•ͳǤͺΨǤ

    ͹ǤͶǤ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”KRAS ͳʹ


    ‰‡ʹͲͳ͹ͲͷͶ͵Ž‹‹ ƒŽ–—†›‡•‹‰
    Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›™ƒ•ƒ’Šƒ•‡ͳȀʹ—Ž–‹ ‡–‡”ǡ‘Ǧ”ƒ†‘‹œ‡†ǡ‘’‡ǦŽƒ„‡Ž•–—†›
    ‘ˆ‘”ƒŽŽ›ƒ†‹‹•–‡”‡†̻ȋ•‘–‘”ƒ•‹„Ȍ‹•—„Œ‡ –•™‹–ŠǤŠ‡’”‹ƒ”›•‘–‘”ƒ•‹„
    ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ ‘’”‹•‡•KRAS ͳʹ—–ƒ–‹‘Ǧ’‘•‹–‹˜‡•—„Œ‡ –•ˆ”‘–Š‡‰‡ʹͲͳ͹ͲͷͶ͵
    •–—†›™Š‘•‡†‹•‡ƒ•‡’”‘‰”‡••‡†ƒˆ–‡”’”‹‘”–Š‡”ƒ’›ȋ‹—‘–Š‡”ƒ’›Ȁ Š‡‘–Š‡”ƒ’›Ȍƒ†™Š‘™‡”‡
    –”‡ƒ–‡†™‹–Šƒ–Ž‡ƒ•–‘‡†‘•‡‘ˆ–Š‡”‡ ‘‡†‡†’Šƒ•‡ʹ†‘•‡ȋʹȌ‘ˆ•‘–‘”ƒ•‹„Ǥƒ–‹‡–•™‡”‡
    ‡”‘ŽŽ‡†„ƒ•‡†‘–Š‡’”‡•‡ ‡‘ˆKRAS ͳʹ—–ƒ–‹‘‹–Š‡‹”–—‘”•ƒ• ‘ˆ‹”‡†„› ‡–”ƒŽ–‹••—‡
    –‡•–‹‰ǤŠ‹• Ž‹‹ ƒŽ•–—†›™ƒ•—•‡†–‘•—’’‘”––Š‡ƒ’’”‘˜ƒŽ‘ˆ̻ȋ•‘–‘”ƒ•‹„Ȍ—†‡”
    ʹͳͶ͸͸ͷǤ

    ͸͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    —ƒ”†ƒ–͵͸ͲšKRAS”‹†‰‹‰–—†›‡•‹‰ˆ‘”KRAS ͳʹ—–ƒ–‹‘
    ”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘ͳͳʹ‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›’ƒ–‹‡–•ȋͺͺǤͻΨ‘ˆͳʹ͸–Š‡
    ’”‹ƒ”›”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘Ȍ™‡”‡–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸ͲšǤŠ‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ
    •–—†›†‹†‘–‹ Ž—†‡’ƒ–‹‡–•‡‰ƒ–‹˜‡ˆ‘”KRAS ͳʹ—–ƒ–‹‘•ƒ†–Š‡”‡ˆ‘”‡†‹†‘–”‡’”‡•‡––Š‡
    —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ‡‰ƒ–‹˜‡’‘”–‹‘‘ˆ–Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡‹–‡†‡†—•‡
    ’‘’—Žƒ–‹‘Ǥ••— Šǡ•—’’Ž‡‡–ƒŽƒ– Š‡†–‹••—‡ƒ†’Žƒ•ƒ•ƒ’Ž‡•™‡”‡‘„–ƒ‹‡†ˆ”‘•—„Œ‡ –•
    ‹‘–Š‡”‰‡ Ž‹‹ ƒŽ•–—†‹‡•ƒ† ‘‡” ‹ƒŽ˜‡†‘”•—•‹‰•—„Œ‡ –•‡Ž‡ –‹‘ ”‹–‡”‹ƒ•‹‹Žƒ”–‘
    –Š‘•‡‘ˆ–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›ƒ†—•‡†–‘‡•–‹ƒ–‡–Š‡’”‡˜ƒŽ‡ ‡‘ˆ’ƒ–‹‡–•’‘•‹–‹˜‡
    ˆ‘”KRAS ͳʹ—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸Ͳš„—–‡‰ƒ–‹˜‡„›–‹••—‡–‡•–‹‰–‘‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ
    ‹’ƒ –‘ˆ–Š‹•’‘’—Žƒ–‹‘‘ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›Ǥ
    a. Clinical Bridging Study Inclusion and Exclusion Criteria
    ŽŽ•—„Œ‡ –•‹–Š‡’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡‹ Ž—†‡†‹–Š‡†‹ƒ‰‘•–‹ •–—†›
    ‡ˆˆ‹ ƒ › ‘Š‘”–‹ˆ–Š‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ„‡Ž‘™™‡”‡‡–Ǥ‹‹Žƒ”Ž›ǡƒŽŽ•—„Œ‡ –•‡‡–‹‰–Š‡•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†› ‘Š‘”–•‡Ž‡ –‹‘ ”‹–‡”‹ƒ„‡Ž‘™ƒ”‡‹ Ž—†‡†Ǥ
    x Inclusion Criteria for Plasma Samples from the Amgen 20170543 Clinical Study Efficacy Cohort
    o —„Œ‡ –‹ Ž—†‡†‹–Š‡’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‹–Š‹ˆ‘”‡† ‘•‡–
    ˆ‘”„Ž‘‘†•ƒ’Ž‡—•‡ˆ‘”†‹ƒ‰‘•–‹ †‡˜‡Ž‘’‡–Ǥ
    o †‡“—ƒ–‡’”‡–”‡ƒ–‡–•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘” —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰ƒ•†‡ˆ‹‡†‹–Š‡
    †‡˜‹ ‡ •–”— –‹‘•ˆ‘”•‡ȋ ȌǤ
    x Inclusion Criteria for Samples for the Diagnostic Study Sensitivity Analysis Prevalence Sub-Study
    ††‹–‹‘ƒŽ•—„Œ‡ –•™‡”‡‹ Ž—†‡†‹–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›‹ˆ–Š‡•‡Ž‡ –‹‘
    ”‹–‡”‹ƒ„‡Ž‘™™‡”‡‡–Ǥ
    o —„Œ‡ –’”‘˜‹†‡†‹ˆ‘”‡† ‘•‡–ˆ‘”„Ž‘‘†ƒ†–‹••—‡•ƒ’Ž‡—•‡ˆ‘”†‡˜‡Ž‘’‡–
    ’—”’‘•‡•Ǥ
    o ƒ–Š‘Ž‘‰‹ ƒŽŽ›†‘ —‡–‡†Ž‘ ƒŽŽ›ƒ†˜ƒ ‡†‘”‡–ƒ•–ƒ–‹ Ǥ
    o —„Œ‡ –•—•–Šƒ˜‡ƒ –‹˜‡†‹•‡ƒ•‡’”‘‰”‡••‹‘ƒ†—•–‘–„‡”‡ ‡‹˜‹‰–Š‡”ƒ’›ƒ––Š‡
    –‹‡‘ˆ„Ž‘‘† ‘ŽŽ‡ –‹‘Ǥ
    o —„Œ‡ –•—•–’”‘˜‹†‡ƒƒ” Š‹˜‡†–—‘”–‹••—‡•ƒ’Ž‡ȋ—•–ƒ‹‡†•Ž‹†‡•ƒ†Ȁ‘”ƒ 
    –‹••—‡„Ž‘  ‘ŽŽ‡ –‡†™‹–Š‹ͷ›‡ƒ”•‘ˆ–Š‡ƒ– Š‡†’Žƒ•ƒ•ƒ’Ž‡Ȍ™‹–Š•—ˆˆ‹ ‹‡––—‘”
    ‘–‡–ƒ†“—ƒ–‹–›ˆ‘”–‡•–‹‰ƒ•†‡ˆ‹‡†„›–Š‡ ‡–”ƒŽ–‡•–‹‰Žƒ„‘”ƒ–‘”›”‡“—‹”‡‡–•Ǥ
    o —„Œ‡ –—•–’”‘˜‹†‡ƒ™Š‘Ž‡„Ž‘‘†‘”’Žƒ•ƒ•’‡ ‹‡–Šƒ–‡‡–•–Š‡”‡“—‹”‡‡–•ˆ‘”
    —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰Ǥ
    b. Follow-up Schedule
    Š‡ —ƒ”†ƒ–͵͸ͲšKRAS ͳʹ—–ƒ–‹‘„”‹†‰‹‰•–—†›‹˜‘Ž˜‡†‘Ž›”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ
    ’Žƒ•ƒ•ƒ’Ž‡•Ǣƒ••— Šǡ‘ƒ††‹–‹‘ƒŽ’ƒ–‹‡–ˆ‘ŽŽ‘™Ǧ—’™ƒ• ‘†— –‡†Ǥ
    c. Clinical Endpoints
    Š‡ Ž‹‹ ƒŽ‡†’‘‹–—•‡†–‘ƒ••‡••̻ȋ•‘–‘”ƒ•‹„Ȍ‡ˆˆ‹ ƒ ›‹–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ
    •–—†›’”‹ƒ”›‘„Œ‡ –‹˜‡™ƒ•‘„Œ‡ –‹˜‡”‡•’‘•‡”ƒ–‡ȋȌ„›”‡•’‘•‡‡˜ƒŽ—ƒ–‹‘ ”‹–‡”‹ƒ‹•‘Ž‹†
    –—‘”•ȋ ȌͳǤͳƒ•ƒ••‡••‡†„›‹†‡’‡†‡–”ƒ†‹‘‰”ƒ’Š‹ ”‡˜‹‡™ȋ ȌǤŠ‡ —ƒ”†ƒ–͵͸Ͳš
    „”‹†‰‹‰•–—†›ˆ‘”’ƒ–‹‡–•™‹–ŠƒKRAS ͳʹ—–ƒ–‹‘—•‡•–Š‡•ƒ‡ Ž‹‹ ƒŽ‡†’‘‹–ˆ‘”‹–•
    ’”‹ƒ”›‘„Œ‡ –‹˜‡Ǥ

    ͸͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    d. Diagnostic Objective and Endpoints
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡‘ˆ–Š‡ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‹•–‘†‡‘•–”ƒ–‡–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ
    —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆ‡–ƒ•–ƒ–‹ ’ƒ–‹‡–•™‹–ŠKRAS ͳʹ—–ƒ–‹‘•ˆ‘”
    –”‡ƒ–‡–™‹–Š̻ȋ•‘–‘”ƒ•‹„ȌǤŠ‡’”‹ƒ”›‡†’‘‹–‹•„› ͳǤͳƒ•ƒ••‡••‡†„›
    Ǥ
     ‘—–ƒ„‹Ž‹–›‘ˆ–Š‡‘Š‘”–ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”KRAS ͳʹ
    —–ƒ–‹‘
    Š‡ —ƒ”†ƒ–͵͸Ͳš Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‹ Ž—†‡†ͳͳʹ‘ˆ–Š‡–‘–ƒŽͳʹ͸ȋͺͻΨȌ’ƒ–‹‡–•‹–Š‡
    ‰‡ʹͲͳ͹ͲͷͶ͵”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ȋFigure 7ȌǤˆ–Š‡•‡ǡ͹ͺȋ͹ͲΨȌ–‡•–‡†’‘•‹–‹˜‡„›
    —ƒ”†ƒ–͵͸Ͳšƒ†™‡”‡‹ Ž—†‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹••‡–ǡ™Š‹Ž‡͵ͳȋʹͺΨȌ–‡•–‡†
    ‡‰ƒ–‹˜‡ǡƒ†͵ȋ͵ΨȌˆƒ‹Ž‡†–‡•–‹‰Ǥ™‘ȋʹȌ‘ˆ–Š‡ͳʹ͸•—„Œ‡ –•‹–Š‡‹‹–‹ƒŽ’”‹ƒ”›•‘–‘”ƒ•‹„
    ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡Žƒ–‡”ˆ‘—†–‘„‡—‡˜ƒŽ—ƒ„Ž‡ˆ‘””‡•’‘•‡†—‡–‘–Š‡ƒ„•‡ ‡‘ˆ
    ”ƒ†‹‘‰”ƒ’Š‹ ƒŽŽ›‡ƒ•—”ƒ„Ž‡Ž‡•‹‘•ƒ–„ƒ•‡Ž‹‡ǤŠ—•ǡƒ–‘–ƒŽ‘ˆͳʹͶ’ƒ–‹‡–•™‡”‡–Š‡ˆ‹ƒŽˆ—ŽŽ
    ƒƒŽ›•‹••‡–ȋ ȌǤ

    
    Figure 7. Guardant360 CDx KRAS G12C Mutation Bridging Study Efficacy Analysis Patient
    Accountability and Analysis Set Definitions
    ‘–‡ǣ”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›•—„‰”‘—’ȋ‰Ȍ•Šƒ†‡†‹‰”‡‡ǤŽ‹‹ ƒŽ‡ˆˆ‹ ƒ › ‘’ƒ”ƒ–‘”•—„‰”‘—’••Šƒ†‡†‹‰”ƒ›Ǥ
    Š‡ —ƒ”†ƒ–͵͸Ͳšƒ••ƒ›ƒ‰”‡‡‡–ƒƒŽ›•‹•‹ Ž—†‡†ͳͺͺ’ƒ–‹‡–•™‹–Š —ƒ”†ƒ–͵͸Ͳšƒ†
    therascreenKRAS ‹–—•‹‰–‹••—‡–‡•–”‡•—Ž–•ˆ”‘„‘–Š–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›
    ƒ†–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›‰”‘—’ȋ Figure 8 Ǥ

    ͸ͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    
    Figure 8. Guardant360 CDx KRAS G12C Assay Agreement Analysis Patient Accountability and
    Analysis Set Definitions
    ‘–‡ǣ••ƒ›ƒ‰”‡‡‡–•—„‰”‘—’ȋȌ•Šƒ†‡†‹‰”‡‡Ǥ

    ‘ ‘”†ƒ ‡‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†therascreenKRAS ‹–—•‹‰‹••—‡


    ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡therascreenKRAS ‹–—•‹‰–‹••—‡ˆ‘”ƒŽŽ
    ƒ– Š‡†’Žƒ•ƒƒ†–‹••—‡•ƒ’Ž‡•ˆ”‘–Š‡‰‡ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›ƒ†–Š‡•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›‰”‘—’‹••Š‘™‹Table 50„‡Ž‘™ǤŠ‹Ž‡ƒŽŽ•ƒ’Ž‡••‘—” ‡†ˆ”‘–Š‡
    ’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡’‘•‹–‹˜‡„›–Š‡therascreenKRAS ‹–ƒ•ƒ
    ‘†‹–‹‘‘ˆ–Š‡‹”‡”‘ŽŽ‡–‹–Š‡ Ž‹‹ ƒŽ•–—†›ǡ–Š‡’”‡˜ƒŽ‡ ‡•–—†›•—„Œ‡ –•™‡”‡”‡ ”—‹–‡†
    ™‹–Š‘—–”‡‰ƒ”†ˆ‘”„‹‘ƒ”‡”•–ƒ–—•ƒ†–Š—• ‘’”‹•‡†„‘–ŠKRAS ͳʹǦ’‘•‹–‹˜‡ƒ†Ǧ‡‰ƒ–‹˜‡
    •—„Œ‡ –•ƒ–ƒƒ–—”ƒŽ’”‡˜ƒŽ‡ ‡ȋFigure 7 Ǥ
    ‘”–Š‡ ‘ ‘”†ƒ ‡ƒƒŽ›•‹•ȋTable 50Ȍǡ™Š‡ƒ••‡••‹‰–Š‡’‘•‹–‹˜‡’‡” ‡–ƒ‰”‡‡‡–ȋȌǡͳͲͺ
    –‹••—‡Ǧ’‘•‹–‹˜‡•ƒ’Ž‡•™‡”‡‡˜ƒŽ—ƒ–‡†ˆ”‘–Š‡’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘Ǥ 
    ƒ††‹–‹‘ǡ‘‡•ƒ’Ž‡–Šƒ–™ƒ•‘–‡˜ƒŽ—ƒ„Ž‡ˆ‘”‡ˆˆ‹ ƒ ›ȋ Figure 7Ȍ™ƒ••–‹ŽŽ ‘•‹†‡”‡†ƒ•’ƒ”–‘ˆ–Š‡
    ‘ ‘”†ƒ ‡ƒƒŽ›•‹•™Š‹ Š”‡•—Ž–•‹ƒ–‘–ƒŽ‘ˆͳͲͻ•ƒ’Ž‡•ˆ‘” ƒŽ —Žƒ–‹‘Ǥˆ–Š‡ͳͲͻ–‹••—‡Ǧ
    ’‘•‹–‹˜‡’ƒ–‹‡–•‹–Š‡’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ǡ͹ͺ•ƒ’Ž‡•™‡”‡’‘•‹–‹˜‡ƒ†͵ͳ
    ™‡”‡‡‰ƒ–‹˜‡„› —ƒ”†ƒ–͵͸ͲšȋFigure 7ƒ†Table 50ȌǤ
    ˆ–Š‡ͺͲ•ƒ’Ž‡•ˆ”‘–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›ǡi.e.ǡ•ƒ’Ž‡•™‹–Š‘—–”‡‰ƒ”†ˆ‘”
    „‹‘ƒ”‡”•–ƒ–—•ƒ† ‘’”‹•‹‰„‘–ŠKRAS ͳʹǦ’‘•‹–‹˜‡ƒ†Ǧ‡‰ƒ–‹˜‡•—„Œ‡ –•ƒ–ƒƒ–—”ƒŽ
    ’”‡˜ƒŽ‡ ‡ǡ͹ʹ™‡”‡‡‰ƒ–‹˜‡„›„‘–Š —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡therascreen KRAS –‡•–—•‹‰
    –‹••—‡ǤŠ‡”‡ƒ‹‹‰ͺ™‡”‡’‘•‹–‹˜‡„›–Š‡therascreen KRAS –‡•–ǡ‘ˆ™Š‹ ŠͶ™‡”‡’‘•‹–‹˜‡
    „›–Š‡ —ƒ”†ƒ–͵͸Ͳšǡƒ†Ͷ™‡”‡‡‰ƒ–‹˜‡„›–Š‡ —ƒ”†ƒ–͵͸ͲšǤƒ’Ž‡•™‹–Š‡‰ƒ–‹˜‡”‡•—Ž–•
    ˆ”‘therascreen KRAS –‡•–™‡”‡—•‡†ˆ‘”‡‰ƒ–‹˜‡’‡” ‡–ƒ‰”‡‡‡–ȋȌ ƒŽ —Žƒ–‹‘
    ȋTable 50 Ǥ

    ͸ͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 50. Concordance Between Guardant360 CDx and therascreen KRAS RGQ PCR Kit using
    Tissue
    therascreen KRAS RGQ therascreen KRAS RGQ
     PCR Kit Positive (CTA) PCR Kit Negative Total
    —ƒ”†ƒ–͵͸Ͳš‘•‹–‹˜‡ȋȌ ͺʹ Ͳ ͺʹ
    ȋΨȌ ȋ͹ͲǤͳȌ ȋͲǤͲȌ ȋͶ͵ǤͶȌ
    —ƒ”†ƒ–͵͸Ͳš‡‰ƒ–‹˜‡ȋȌ ͵ͷ ͹ʹ ͳͲ͹
    ȋΨȌ ȋʹͻǤͻȌ ȋͳͲͲǤͲȌ ȋͷ͸Ǥ͸Ȍ
    ‘–ƒŽ ͳͳ͹ ͹ʹ ͳͺͳ
    ‘•‹–‹˜‡‡” ‡–‰”‡‡‡–ȋͻͷΨ Ȍ ͹ͲǤͳΨ
    ȋ͸ͲǤͻΨȂ͹ͺǤʹΨȌ
    ‡‰ƒ–‹˜‡‡” ‡–‰”‡‡‡–ȋͻͷΨ Ȍ ͳͲͲΨ
    ȋͻͷǤͲΨȂͳͲͲǤͲΨȌ

    –—†›‘’—Žƒ–‹‘‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡Ž‹‹ ƒŽƒ”ƒ‡–‡”•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ


    ”‹†‰‹‰–—†›ˆ‘”KRAS ͳʹ—–ƒ–‹‘•
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•‡”‘ŽŽ‡†‹–Š‡‰‡ʹͲͳ͹ͲͷͶ͵
    Ž‹‹ ƒŽ•–—†›™‡”‡ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡–‘–Š‡†‹ƒ‰‘•–‹ •–—†›’‘’—Žƒ–‹‘•ƒ•†‡ˆ‹‡†„›
    —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•Ǥ
    ••Š‘™‹Table 51ƒ†Table 52ǡ–Š‡ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ȋ‰Ȍ
    †‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ • Ž‘•‡Ž›”‡•‡„Ž‡–Š‘•‡‘ˆ–Š‡‘˜‡”ƒŽŽ”‡‰‹•–”ƒ–‹‘
    ’‘’—Žƒ–‹‘ȋ ȌǤ‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ’ƒ–‹‡–•™‹–Š’Žƒ•ƒƒ˜ƒ‹Žƒ„Ž‡
    ˆ‘”–‡•–‹‰‹–Š‹•†‹ƒ‰‘•–‹ •–—†›ȋ‰Ȍƒ†–Š‘•‡™‹–Š‘—–ȋ‰Ǧ™Š‹ Š‹•ƒ ‘„‹ƒ–‹‘‘ˆ
    •ƒ’Ž‡•‘––‡•–‡†ƒ†–Š‘•‡ˆ‘”™Š‘ —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰ˆƒ‹Ž‡†Ȍ™‡”‡ƒŽ•‘ ‘’ƒ”ƒ„Ž‡–‘ 
    ƒ†‰Ǥ

    Table 51. Baseline Demographics of the FAS and Sub-Groups


     FAS gCEAS gAS gAS-UNK
    Sex n (%)
    ƒŽ‡ ͸͵ȋͷͲǤͲȌ ͵͸ȋͶ͸ǤʹȌ ͷͺȋͷͳǤͺȌ ͹ȋͶͳǤʹȌ
    ‡ƒŽ‡ ͸͵ȋͷͲǤͲȌ Ͷʹȋͷ͵ǤͺȌ ͷͶȋͶͺǤʹȌ ͳͲȋͷͺǤͺȌ
    Ethnicity - n (%)
    ‹•’ƒ‹ ‘”ƒ–‹‘ ʹȋͳǤ͸Ȍ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͳȋͷǤͻȌ
    ‘– ‹•’ƒ‹ ‘”ƒ–‹‘ ͳͳ͸ȋͻʹǤͳȌ ͹͵ȋͻ͵Ǥ͸Ȍ ͳͲͶȋͻʹǤͻȌ ͳͶȋͺʹǤͶ 
    ‹••‹‰ ͺȋ͸Ǥ͵Ȍ ͶȋͷǤͳȌ ͹ȋ͸Ǥ͵Ȍ ʹȋͳͳǤͺȌ
    Race - n (%)
    ‡”‹ ƒ †‹ƒ‘”Žƒ•ƒƒ–‹˜‡ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲ 
    •‹ƒ ͳͻȋͳͷǤͳȌ ͳͳȋͳͶǤͳȌ ͳͻȋͳ͹ǤͲȌ ͲȋͲǤͲȌ
    Žƒ ‘”ˆ”‹ ƒ‡”‹ ƒ ʹȋͳǤ͸Ȍ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͳȋͷǤͻȌ
    ƒ–‹˜‡ ƒ™ƒ‹‹ƒ‘”–Š‡”ƒ ‹ˆ‹  ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    •Žƒ†‡”
    Š‹–‡ ͳͲ͵ȋͺͳǤ͹Ȍ ͸ͷȋͺ͵Ǥ͵Ȍ ͻͲȋͺͲǤͶȌ ͳ͸ȋͻͶǤͳȌ
    —Ž–‹’Ž‡ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –Š‡” ʹȋͳǤ͸Ȍ ͳȋͳǤ͵Ȍ ʹȋͳǤͺȌ ͲȋͲǤͲȌ

    ͹Ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     FAS gCEAS gAS gAS-UNK
    Age (years)
     ͳʹ͸ ͹ͺ ͳͳʹ ͳ͹
    ‡ƒ ͸ʹǤͻ ͸ʹǤ͹ ͸ʹǤ͸ ͸ͷǤ͵
     ͻǤ͵ ͻǤ͹ ͻǤͶ ͹Ǥͻ
    ‡†‹ƒ ͸͵Ǥͷ ͸͵ǤͲ ͸͵ǤͲ ͸ͷǤͲ
    ͳǡ͵ ͷ͸ǤͲǡ͹ͲǤͲ ͷ͸ǤͲǡ͹ʹǤͲ ͷ͸ǤͲǡ͹ͲǤͲ ͸ͳǤͲǡ͹ͲǤͲ
    ‹ǡƒš ͵͹ǡͺͲ ͵͹ǡ͹ͺ ͵͹ǡͺͲ Ͷ͸ǡ͹ͻ
    Age Group (years)
    ͳͺǦ͸Ͷ›‡ƒ”• ͸͹ȋͷ͵ǤʹȌ Ͷ͵ȋͷͷǤͳȌ ͸ͳȋͷͶǤͷȌ ͹ȋͶͳǤʹȌ
    ͸ͷǦ͹Ͷ›‡ƒ”• Ͷͻȋ͵ͺǤͻȌ ʹͻȋ͵͹ǤʹȌ ͶͶȋ͵ͻǤ͵Ȍ ͹ȋͶͳǤʹȌ
    ͹ͷǦͺͶ›‡ƒ”• ͳͲȋ͹ǤͻȌ ͸ȋ͹Ǥ͹Ȍ ͹ȋ͸Ǥ͵Ȍ ͵ȋͳ͹Ǥ͸Ȍ
    ηͺͷ›‡ƒ”• ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ

    Table 52. Baseline Clinical Characteristics of the FAS and Sub-Groups


     FAS gCEAS gAS gAS-UNK
    ECOG status at baseline - n (%)
    Ͳ ͵ͺȋ͵ͲǤʹȌ ʹͲȋʹͷǤ͸Ȍ ͵ͷȋ͵ͳǤ͵Ȍ ͷȋʹͻǤͶȌ
    ͳ ͺͺȋ͸ͻǤͺȌ ͷͺȋ͹ͶǤͶȌ ͹͹ȋ͸ͺǤͺȌ ͳʹȋ͹ͲǤ͸Ȍ
    ʹ ͲȋͲǤͲ  ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲ 
    Weight (kg)
     ͳʹ͸ ͹ͺ ͳͳʹ ͳ͹
    ‡ƒ ͹ͳǤͲͺ ͹ͳǤͳͺ ͹ͳǤ͵ͷ ͸͹Ǥͻʹ
     ͳ͹ǤͳͶ ͳ͹Ǥ͵ͺ ͳ͹ǤͲ͸ ͳͺǤ͵Ͳ
    ‡†‹ƒ ͹ͲǤ͸ͷ ͹ͲǤͳͷ ͹ͳǤͲͲ ͹ͲǤͲͲ
    ͳǡ͵ ͷͺǡͺ͵ ͷͺǡͺ͵ ͷͺǡͺ͵ ͷ͹ǡͺʹ
    ‹ǡƒš ͵͹ǡͳʹ͵ ͵͹ǡͳʹ͵ ͵͹ǡͳʹ͵ ͶͲǡͳͲͺ
    Height (cm)
     ͳʹ͵ ͹͹ ͳͳͲ ͳ͸
    ‡ƒ ͳ͸ͺ ͳ͸ͺ ͳ͸ͺ ͳ͸ͺ
     ͻǤʹ ͺǤͻ ͺǤͻ ͳͳǤ͸
    ‡†‹ƒ ͳ͸ͻ ͳ͸ͺ ͳ͸ͻ ͳ͸ͺ
    ͳǡ͵ ͳ͸ͳǡͳ͹ͷ ͳ͸ͳǡͳ͹ͷ ͳ͸ͳǡͳ͹ͷ ͳͷ͸ǡͳ͹ͷ
    ‹ǡƒš ͳͶ͸ǡͳͺͺ ͳͷͳǡͳͺͺ ͳͷͳǡͳͺͺ ͳͶ͸ǡͳͺ͵
    Prior line of anti-cancer therapy - n (%)
    Ͳ ͲȋͲǤͲ  ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲ 
    ͳ ͷͶȋͶʹǤͻȌ ͵͵ȋͶʹǤ͵Ȍ ͶͺȋͶʹǤͻȌ ͺȋͶ͹ǤͳȌ
    ʹ ͶͶȋ͵ͶǤͻȌ ʹͺȋ͵ͷǤͻȌ ͵ͺȋ͵͵ǤͻȌ ͹ȋͶͳǤʹȌ
    ͵ ʹͺȋʹʹǤʹȌ ͳ͹ȋʹͳǤͺȌ ʹ͸ȋʹ͵ǤʹȌ ʹȋͳͳǤͺȌ
    ηͶ ͲȋͲǤͲ  ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲ 
    ‡†‹ƒȋ—„‡”‘ˆ’”‹‘”Ž‹‡•Ȍ ʹ ʹ ʹ ʹ

    ͹ͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     FAS gCEAS gAS gAS-UNK
    Type of prior anti-cancer therapy - n (%)
    Š‡‘–Š‡”ƒ’› ͳͳͷȋͻͳǤ͵Ȍ ͹͵ȋͻ͵Ǥ͸Ȍ ͳͲͶȋͻʹǤͻȌ ͳͶȋͺʹǤͶȌ
    Žƒ–‹—Ǧ„ƒ•‡ Š‡‘–Š‡”ƒ’› ͳͳ͵ȋͺͻǤ͹Ȍ ͹ʹȋͻʹǤ͵Ȍ ͳͲʹȋͻͳǤͳȌ ͳͶȋͺʹǤͶȌ
    —‘–Š‡”ƒ’› ͳͳ͸ȋͻʹǤͳȌ ͹ʹȋͻʹǤ͵Ȍ ͳͲʹȋͻͳǤͳȌ ͳ͸ȋͻͶǤͳȌ
    Š‡ ’‘‹–‹Š‹„‹–‘” ͳͳ͸ȋͻʹǤͳȌ ͹ʹȋͻʹǤ͵Ȍ ͳͲʹȋͻͳǤͳȌ ͳ͸ȋͻͶǤͳȌ
    –‹Ǧͳ‘”ƒ–‹Ǧͳ ͳͳͷȋͻͳǤ͵Ȍ ͹ʹȋͻʹǤ͵Ȍ ͳͲͳȋͻͲǤʹȌ ͳ͸ȋͻͶǤͳȌ
    Žƒ–‹—Ǧ„ƒ•‡ Š‡‘–Š‡”ƒ’›ƒ† ͳͲʹȋͺͳǤͲȌ ͸͸ȋͺͶǤ͸Ȍ ͻͳȋͺͳǤ͵Ȍ ͳ͵ȋ͹͸ǤͷȌ
    ƒ–‹Ǧͳ‘”ƒ–‹Ǧͳ 
    ‘”‘ƒŽ–Š‡”ƒ’› ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    ƒ”‰‡–‡†„‹‘Ž‘‰‹ • ͵Ͳȋʹ͵ǤͺȌ ͳ͹ȋʹͳǤͺȌ ʹͺȋʹͷǤͲȌ ʹȋͳͳǤͺȌ
    –‹Ǧ „‹‘Ž‘‰‹ ƒŽ–Š‡”ƒ’› ʹͷȋͳͻǤͺȌ ͳͷȋͳͻǤʹȌ ʹͶȋʹͳǤͶȌ ͳȋͷǤͻȌ
    ƒ”‰‡–‡†•ƒŽŽ‘Ž‡ —Ž‡• ͻȋ͹ǤͳȌ ͵ȋ͵ǤͺȌ ͸ȋͷǤͶȌ ͵ȋͳ͹Ǥ͸Ȍ
    –Š‡” ͳȋͲǤͺȌ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    Disease stage at initial diagnosis - n (%)
    –ƒ‰‡  ͳͳȋͺǤ͹Ȍ ͸ȋ͹Ǥ͹Ȍ ͳͲȋͺǤͻȌ ͳȋͷǤͻȌ
    –ƒ‰‡  ͳͶȋͳͳǤͳȌ ͸ȋ͹Ǥ͹Ȍ ͳʹȋͳͲǤ͹Ȍ ʹȋͳͳǤͺȌ
    –ƒ‰‡  ʹʹȋͳ͹ǤͷȌ ͳͻȋʹͶǤͶȌ ʹͳȋͳͺǤͺȌ ͳȋͷǤͻȌ
    –ƒ‰‡  ͹ͺȋ͸ͳǤͻȌ Ͷ͸ȋͷͻǤͲȌ ͸ͺȋ͸ͲǤ͹Ȍ ͳ͵ȋ͹͸ǤͷȌ
    ‹••‹‰ ͳȋͲǤͺȌ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    Disease stage at screening - n (%)
    –ƒ‰‡  ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –ƒ‰‡  ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –ƒ‰‡  ͷȋͶǤͲȌ ͶȋͷǤͳȌ ͷȋͶǤͷȌ ͲȋͲǤͲȌ
    –ƒ‰‡  ͳʹͳȋͻ͸ǤͲȌ ͹ͶȋͻͶǤͻȌ ͳͲ͹ȋͻͷǤͷȌ ͳ͹ȋͳͲͲǤͲȌ
    Differentiation - n (%)
    ‡ŽŽ†‹ˆˆ‡”‡–‹ƒ–‡† ͸ȋͶǤͺȌ ͶȋͷǤͳȌ Ͷȋ͵Ǥ͸Ȍ ʹȋͳͳǤͺȌ
    ‘†‡”ƒ–‡Ž›†‹ˆˆ‡”‡–‹ƒ–‡† ͳͷȋͳͳǤͻȌ ͸ȋ͹Ǥ͹Ȍ ͳʹȋͳͲǤ͹Ȍ Ͷȋʹ͵ǤͷȌ
    ‘‘”Ž›†‹ˆˆ‡”‡–‹ƒ–‡† ʹͶȋͳͻǤͲȌ ͳ͸ȋʹͲǤͷȌ ͳͻȋͳ͹ǤͲȌ ͷȋʹͻǤͶȌ
    †‹ˆˆ‡”‡–‹ƒ–‡† ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –Š‡” ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    ‘™ ͺͳȋ͸ͶǤ͵Ȍ ͷʹȋ͸͸Ǥ͹Ȍ ͹͹ȋ͸ͺǤͺȌ ͸ȋ͵ͷǤ͵Ȍ
    PD-L1 protein expression - n (%)
    δͳΨ ͵͵ȋʹ͸ǤʹȌ ͳͺȋʹ͵ǤͳȌ ͵Ͳȋʹ͸ǤͺȌ ͵ȋͳ͹Ǥ͸Ȍ
    ηͳΨƒ†δͷͲΨ ʹͶȋͳͻǤͲȌ ͳ͸ȋʹͲǤͷȌ ʹʹȋͳͻǤ͸Ȍ ͵ȋͳ͹Ǥ͸Ȍ
    ηͷͲΨ ͵ͷȋʹ͹ǤͺȌ ʹͶȋ͵ͲǤͺȌ ͵ͳȋʹ͹Ǥ͹Ȍ ͷȋʹͻǤͶȌ
    ‘™ ͵Ͷȋʹ͹ǤͲȌ ʹͲȋʹͷǤ͸Ȍ ʹͻȋʹͷǤͻȌ ͸ȋ͵ͷǤ͵Ȍ
    Histopathology type - n (%)
    “—ƒ‘—• ͳȋͲǤͺȌ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    †‡‘•“—ƒ‘—• ƒ” ‹‘ƒ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    “—ƒ‘—• ‡ŽŽ ƒ” ‹‘ƒ ͳȋͲǤͺȌ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    ‘Ǧ•“—ƒ‘—• ͳʹͷȋͻͻǤʹȌ ͹͹ȋͻͺǤ͹Ȍ ͳͳͳȋͻͻǤͳȌ ͳ͹ȋͳͲͲǤͲȌ
    †‡‘ ƒ” ‹‘ƒ ͳʹͲȋͻͷǤʹȌ ͹ͷȋͻ͸ǤʹȌ ͳͲ͸ȋͻͶǤ͸Ȍ ͳ͸ȋͻͶǤͳȌ
    — ‹‘—• ͺȋ͸Ǥ͵Ȍ ͷȋ͸ǤͶȌ ͺȋ͹ǤͳȌ ͲȋͲǤͲȌ
    ƒ”‰‡ ‡ŽŽ ƒ” ‹‘ƒ ͵ȋʹǤͶȌ ʹȋʹǤ͸Ȍ ͵ȋʹǤ͹Ȍ ͳȋͷǤͻȌ
    ”‘ Š‘ƒŽ˜‡‘Žƒ” ƒ” ‹‘ƒ ʹȋͳǤ͸Ȍ ͲȋͲǤͲȌ ʹȋͳǤͺȌ ͲȋͲǤͲȌ
    ƒ” ‘ƒ–‘‹† ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    †‹ˆˆ‡”‡–‹ƒ–‡† ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –Š‡” ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ

    ͹ʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     FAS gCEAS gAS gAS-UNK
    Metastatic - n (%)
    ‡• ͳʹʹȋͻ͸ǤͺȌ ͹ͶȋͻͶǤͻȌ ͳͲͺȋͻ͸ǤͶȌ ͳ͹ȋͳͲͲǤͲȌ
    ‘ Ͷȋ͵ǤʹȌ ͶȋͷǤͳȌ Ͷȋ͵Ǥ͸Ȍ ͲȋͲǤͲȌ
    Number of body sites of metastatic disease - n (%)
    Ͳ Ͷȋ͵ǤʹȌ ͶȋͷǤͳȌ Ͷȋ͵Ǥ͸Ȍ ͲȋͲǤͲȌ
    ͳ ͷͳȋͶͲǤͷȌ ʹ͸ȋ͵͵Ǥ͵Ȍ Ͷ͸ȋͶͳǤͳȌ ͹ȋͶͳǤʹȌ
    ʹ ͵Ͳȋʹ͵ǤͺȌ ʹͲȋʹͷǤ͸Ȍ ʹͺȋʹͷǤͲȌ ʹȋͳͳǤͺȌ
    ͵ ʹͶȋͳͻǤͲȌ ͳ͹ȋʹͳǤͺȌ ʹͳȋͳͺǤͺȌ ͵ȋͳ͹Ǥ͸Ȍ
    ε͵ ͳ͹ȋͳ͵ǤͷȌ ͳͳȋͳͶǤͳȌ ͳ͵ȋͳͳǤ͸Ȍ ͷȋʹͻǤͶȌ
    Liver metastasis (n%)
    ‡• ʹ͸ȋʹͲǤ͸Ȍ ͳ͹ȋʹͳǤͺȌ ʹͳȋͳͺǤͺȌ ͹ȋͶͳǤʹȌ
    ‘ ͳͲͲȋ͹ͻǤͶȌ ͸ͳȋ͹ͺǤʹȌ ͻͳȋͺͳǤ͵Ȍ ͳͲȋͷͺǤͺȌ
    Brain metastasis (n%)
    ‡• ʹ͸ȋʹͲǤ͸Ȍ ͳ͹ȋʹͳǤͺȌ ʹʹȋͳͻǤ͸Ȍ ͷȋʹͻǤͶȌ
    ‘ ͳͲͲȋ͹ͻǤͶȌ ͸ͳȋ͹ͺǤʹȌ ͻͲȋͺͲǤͶȌ ͳʹȋ͹ͲǤ͸Ȍ
    Bone metastasis (n%)
    ‡• ͸ͳȋͶͺǤͶȌ ͶͳȋͷʹǤ͸Ȍ ͷʹȋͶ͸ǤͶȌ ͳͲȋͷͺǤͺȌ
    ‘ ͸ͷȋͷͳǤ͸Ȍ ͵͹ȋͶ͹ǤͶȌ ͸Ͳȋͷ͵Ǥ͸Ȍ ͹ȋͶͳǤʹȌ
    Smoking history - n (%)
    ‡˜‡” ͸ȋͶǤͺȌ ͶȋͷǤͳȌ ͸ȋͷǤͶȌ ͲȋͲǤͲȌ
    —””‡– ͳͷȋͳͳǤͻȌ ͹ȋͻǤͲȌ ͳͶȋͳʹǤͷȌ ͵ȋͳ͹Ǥ͸Ȍ
    ‘”‡” ͳͲʹȋͺͳǤͲȌ ͸͸ȋͺͶǤ͸Ȍ ͺͻȋ͹ͻǤͷȌ ͳͶȋͺʹǤͶȌ
    ‹••‹‰ ͵ȋʹǤͶȌ ͳȋͳǤ͵Ȍ ͵ȋʹǤ͹Ȍ ͲȋͲǤͲȌ
    Region n (%)
    ‘”–Š‡”‹ ƒ ͹ͻȋ͸ʹǤ͹Ȍ ͷͲȋ͸ͶǤͳȌ ͸ͺȋ͸ͲǤ͹Ȍ ͳʹȋ͹ͲǤ͸Ȍ
    —”‘’‡ ͵Ͳȋʹ͵ǤͺȌ ͳͺȋʹ͵ǤͳȌ ʹ͹ȋʹͶǤͳȌ ͷȋʹͻǤͶȌ
    •‹ƒ ͳʹȋͻǤͷȌ ͹ȋͻǤͲȌ ͳʹȋͳͲǤ͹Ȍ ͲȋͲǤͲȌ
    ‡•–‘ˆ–Š‡™‘”Ž† ͷȋͶǤͲȌ ͵ȋ͵ǤͺȌ ͷȋͶǤͷȌ ͲȋͲǤͲȌ
    Best response to last prior line of therapy - n (%)
    ‘’Ž‡–‡”‡•’‘•‡ ͳȋͲǤͺȌ ͳȋͳǤ͵Ȍ ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    ƒ”–‹ƒŽ”‡•’‘•‡ ͳʹȋͻǤͷȌ ͻȋͳͳǤͷȌ ͳʹȋͳͲǤ͹Ȍ ͳȋͷǤͻȌ
    –ƒ„Ž‡†‹•‡ƒ•‡ ͵͵ȋʹ͸ǤʹȌ ͳͻȋʹͶǤͶȌ ʹͺȋʹͷǤͲȌ ͷȋʹͻǤͶȌ
    ”‘‰”‡••‹˜‡†‹•‡ƒ•‡ Ͷͺȋ͵ͺǤͳȌ ͵͵ȋͶʹǤ͵Ȍ ͶͶȋ͵ͻǤ͵Ȍ ͷȋʹͻǤͶȌ
    ‡˜ƒŽ—ƒ„Ž‡ ͳȋͲǤͺȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͳȋͷǤͻȌ
    ‘™Ȁ‘–ƒ’’Ž‹ ƒ„Ž‡Ȁ‘– ʹ͹ȋʹͳǤͶȌ ͳͷȋͳͻǤʹȌ ʹ͵ȋʹͲǤͷȌ ͷȋʹͻǤͶȌ
    †‘‡
    ‹••‹‰ Ͷȋ͵ǤʹȌ ͳȋͳǤ͵Ȍ Ͷȋ͵Ǥ͸Ȍ ͲȋͲǤͲȌ

    ‘ƒ••‡••’‘–‡–‹ƒŽ„‹ƒ•ƒ”‹•‹‰ˆ”‘’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„‹Ž‹–›ǡ„ƒ•‡Ž‹‡†‡‘‰”ƒ’Š‹ ‹ˆ‘”ƒ–‹‘
    ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ†‹•‡ƒ•‡ Šƒ”ƒ –‡”‹•–‹ •‘ˆ•—„Œ‡ –•™‹–Šƒ˜ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–ȋ‰ǦȌ
    ƒ†–Š‘•‡™‹–Š‘—–ȋ‰ǦȌ™‡”‡ ‘’ƒ”‡†ƒ†–Š‡ƒ••‘ ‹ƒ–‡†’˜ƒŽ—‡”‡’‘”–‡†‹Table 53ƒ†
    Table 54Ǥ‘‡ƒ‹‰ˆ—Ž†‹ˆˆ‡”‡ ‡•™‡”‡‘„•‡”˜‡†Ǥ

    Table 53. Comparison of Baseline Demographics between gAS-E and gAS-Unk


     gAS-E gAS-Unk p-value
    ‡šǦȋΨȌ
    ƒŽ‡ ͷ͸ȋͷͳǤͶȌ ͹ȋͶͳǤʹȌ
    ͲǤͶ͵ͶͲ
    ‡ƒŽ‡ ͷ͵ȋͶͺǤ͸Ȍ ͳͲȋͷͺǤͺȌ
    
    ͹͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     gAS-E gAS-Unk p-value
    –Š‹ ‹–›ǦȋΨȌ
    ‹•’ƒ‹ ‘”ƒ–‹‘ ͳȋͲǤͻȌ ͳȋͷǤͻȌ
    ͲǤʹ͵ͻͲ
    ‘– ‹•’ƒ‹ ‘”ƒ–‹‘ ͳͲʹȋͻ͵Ǥ͸Ȍ ͳͶȋͺʹǤͶȌ
    
    ƒ ‡ǦȋΨȌ
    ‡”‹ ƒ †‹ƒ‘”Žƒ•ƒƒ–‹˜‡ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    •‹ƒ ͳͻȋͳ͹ǤͶȌ ͲȋͲǤͲȌ
    Žƒ ‘”ˆ”‹ ƒ‡”‹ ƒ ͳȋͲǤͻȌ ͳȋͷǤͻȌ
    ƒ–‹˜‡ ƒ™ƒ‹‹ƒ‘”–Š‡”ƒ ‹ˆ‹  •Žƒ†‡” ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲǤͲ͹͸ͻ
    Š‹–‡ ͺ͹ȋ͹ͻǤͺȌ ͳ͸ȋͻͶǤͳȌ
    —Ž–‹’Ž‡ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –Š‡” ʹȋͳǤͺȌ ͲȋͲǤͲȌ
    
    ‰‡‰”‘—’ǦȋΨȌ
    ͳͺǦ͸Ͷ›‡ƒ”• ͸ͲȋͷͷǤͲȌ ͹ȋͶͳǤʹȌ
    ͸ͷǦ͹Ͷ›‡ƒ”• Ͷʹȋ͵ͺǤͷȌ ͹ȋͶͳǤʹȌ
    ͲǤʹ͵ͷͶ
    ͹ͷǦͺͶ›‡ƒ”• ͹ȋ͸ǤͶȌ ͵ȋͳ͹Ǥ͸Ȍ
    εαͺͷ›‡ƒ”• ͲȋͲǤͲȌ ͲȋͲǤͲȌ

    Table 54. Comparison of Baseline Clinical Characteristics between gAS-E and gAS-Unk
     gAS-E gAS-Unk p-value
     •–ƒ–—•ƒ–„ƒ•‡Ž‹‡ƒǦȋΨ 
    Ͳ ͵͵ȋ͵ͲǤ͵Ȍ ͷȋʹͻǤͶȌ
    ͳ ͹͸ȋ͸ͻǤ͹Ȍ ͳʹȋ͹ͲǤ͸Ȍ ͲǤͻͶʹͷ
    ʹ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    
    ‡‹‰Š–ȋ‰Ȍ†
    ‡ƒ ͹ͳǤͷ͹ ͸͹Ǥͻʹ ͲǤͶͳͷͺ
    
    ‡‹‰Š–ȋ Ȍ†
    ‡ƒ ͳ͸ͺǤͲͲ ͳ͸͸Ǥ͹͵ ͲǤ͸Ͳͺͻ
    
    ”‹‘”Ž‹‡‘ˆƒ–‹Ǧ ƒ ‡”–Š‡”ƒ’›ǦȋΨȌ
    Ͳ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    ͳ Ͷ͸ȋͶʹǤʹȌ ͺȋͶ͹ǤͳȌ
    ʹ ͵͹ȋ͵͵ǤͻȌ ͹ȋͶͳǤʹȌ ͲǤͷ͵ͲͶ
    ͵ ʹ͸ȋʹ͵ǤͻȌ ʹȋͳͳǤͺȌ
    εαͶ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    

    ͹Ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     gAS-E gAS-Unk p-value
    ›’‡‘ˆ’”‹‘”ƒ–‹Ǧ ƒ ‡”–Š‡”ƒ’›„ǡ‡ǦȋΨȌ
    Š‡‘–Š‡”ƒ’› ͳͲͳȋͻʹǤ͹Ȍ ͳͶȋͺʹǤͶȌ ͲǤͳ͸ͻͲ
    —‘–Š‡”ƒ’› ͳͲͲȋͻͳǤ͹Ȍ ͳ͸ȋͻͶǤͳȌ ͳǤͲͲͲͲ
    Žƒ–‹—Ǧ„ƒ•‡ Š‡‘–Š‡”ƒ’›ƒ†ƒ–‹Ǧͳ‘”ƒ–‹
    ͺͻȋͺͳǤ͹Ȍ ͳ͵ȋ͹͸ǤͷȌ ͲǤ͹͵ͻͷ
    Ǧͳ 
    ‘”‘ƒŽ–Š‡”ƒ’› ͲȋͲǤͲȌ ͲȋͲǤͲȌ 
    ƒ”‰‡–‡†„‹‘Ž‘‰‹ • ʹͺȋʹͷǤ͹Ȍ ʹȋͳͳǤͺȌ ͲǤ͵ͷ͹ͷ
    ƒ”‰‡–‡†•ƒŽŽ‘Ž‡ —Ž‡• ͸ȋͷǤͷȌ ͵ȋͳ͹Ǥ͸Ȍ ͲǤͳͲʹͺ
    –Š‡” ͳȋͲǤͻȌ ͲȋͲǤͲȌ ͳǤͲͲͲͲ
    
    ‹•‡ƒ•‡•–ƒ‰‡ƒ–‹‹–‹ƒŽ†‹ƒ‰‘•‹•ǦȋΨȌ
    –ƒ‰‡  ͳͲȋͻǤʹȌ ͳȋͷǤͻȌ
    –ƒ‰‡  ͳʹȋͳͳǤͲȌ ʹȋͳͳǤͺȌ
    ͲǤ͸ͳͲͶ
    –ƒ‰‡  ʹͳȋͳͻǤ͵Ȍ ͳȋͷǤͻȌ
    –ƒ‰‡  ͸ͷȋͷͻǤ͸Ȍ ͳ͵ȋ͹͸ǤͷȌ
    
    ‹•‡ƒ•‡•–ƒ‰‡ƒ–• ”‡‡‹‰ǦȋΨȌ
    –ƒ‰‡  ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –ƒ‰‡  ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    ͳǤͲͲͲͲ
    –ƒ‰‡  ͷȋͶǤ͸Ȍ ͲȋͲǤͲȌ
    –ƒ‰‡  ͳͲͶȋͻͷǤͶȌ ͳ͹ȋͳͲͲǤͲȌ
    
    ‹ˆˆ‡”‡–‹ƒ–‹‘ǦȋΨȌ
    ‡ŽŽ†‹ˆˆ‡”‡–‹ƒ–‡† Ͷȋ͵Ǥ͹Ȍ ʹȋͳͳǤͺȌ
    ‘†‡”ƒ–‡Ž›†‹ˆˆ‡”‡–‹ƒ–‡† ͳͳȋͳͲǤͳȌ Ͷȋʹ͵ǤͷȌ
    ‘‘”Ž›†‹ˆˆ‡”‡–‹ƒ–‡† ͳͻȋͳ͹ǤͶȌ ͷȋʹͻǤͶȌ
    ͲǤͲʹ͵ͷ
    †‹ˆˆ‡”‡–‹ƒ–‡† ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –Š‡” ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    ‘™ ͹ͷȋ͸ͺǤͺȌ ͸ȋ͵ͷǤ͵Ȍ
    
    Ǧͳ’”‘–‡‹‡š’”‡••‹‘Ǧ Ψ Ȍ
    δͳΨ ͵Ͳȋʹ͹ǤͷȌ ͵ȋͳ͹Ǥ͸Ȍ
    εαͳΨƒ†δͷͲΨ ʹͳȋͳͻǤ͵Ȍ ͵ȋͳ͹Ǥ͸Ȍ
    ͲǤ͹ͻ͸Ͳ
    εαͷͲΨ ͵Ͳȋʹ͹ǤͷȌ ͷȋʹͻǤͶȌ
    ‘™ ʹͺȋʹͷǤ͹Ȍ ͸ȋ͵ͷǤ͵Ȍ
    
    ‹•–‘’ƒ–Š‘Ž‘‰›–›’‡ǦȋΨȌ
    “—ƒ‘—• ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    ‘Ǧ•“—ƒ‘—• ͳͲͺȋͻͻǤͳȌ ͳ͹ȋͳͲͲǤͲȌ ͳǤͲͲͲͲ
    –Š‡” ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    
    ‡–ƒ•–ƒ–‹ ǦȋΨȌ
    ‡• ͳͲͷȋͻ͸Ǥ͵Ȍ ͳ͹ȋͳͲͲǤͲȌ
    ͳǤͲͲͲͲ
    ‘ Ͷȋ͵Ǥ͹Ȍ ͲȋͲǤͲȌ
    

    ͹ͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     gAS-E gAS-Unk p-value
    —„‡”‘ˆ„‘†›•‹–‡•‘ˆ‡–ƒ•–ƒ–‹ †‹•‡ƒ•‡ǦȋΨȌ
    Ͳ Ͷȋ͵Ǥ͹Ȍ ͲȋͲǤͲȌ
    ͳ ͶͶȋͶͲǤͶȌ ͹ȋͶͳǤʹȌ
    ʹ ʹͺȋʹͷǤ͹Ȍ ʹȋͳͳǤͺȌ ͲǤ͵ͲͲʹ
    ͵ ʹͳȋͳͻǤ͵Ȍ ͵ȋͳ͹Ǥ͸Ȍ
    ε͵ ͳʹȋͳͳǤͲȌ ͷȋʹͻǤͶȌ
    
    ‹˜‡”‡–ƒ•–ƒ•‹•ǦȋΨȌ
    ‡• ͳͻȋͳ͹ǤͶȌ ͹ȋͶͳǤʹȌ
    ͲǤͲͶ͸ͻ
    ‘ ͻͲȋͺʹǤ͸Ȍ ͳͲȋͷͺǤͺȌ
    
    ”ƒ‹‡–ƒ•–ƒ•‹•ǦȋΨȌ
    ‡• ʹͳȋͳͻǤ͵Ȍ ͷȋʹͻǤͶȌ
    ͲǤ͵Ͷʹͻ
    ‘ ͺͺȋͺͲǤ͹Ȍ ͳʹȋ͹ͲǤ͸Ȍ
    
    ‘‡‡–ƒ•–ƒ•‹•ǦȋΨȌ
    ‡• ͷͳȋͶ͸ǤͺȌ ͳͲȋͷͺǤͺȌ
    ͲǤ͵ͷͷͺ
    ‘ ͷͺȋͷ͵ǤʹȌ ͹ȋͶͳǤʹȌ
    
    ‘‹‰Š‹•–‘”›ǦȋΨȌ
    ‡˜‡” ͸ȋͷǤͷȌ ͲȋͲǤͲȌ
    —””‡– ͳʹȋͳͳǤͲȌ ͵ȋͳ͹Ǥ͸Ȍ ͲǤͷͷͲͶ
    ‘”‡” ͺͺȋͺͲǤ͹Ȍ ͳͶȋͺʹǤͶȌ
    
    ‡‰‹‘ǦȋΨȌ
    ‘”–Š‡”‹ ƒ ͸͹ȋ͸ͳǤͷȌ ͳʹȋ͹ͲǤ͸Ȍ
    —”‘’‡ ʹͷȋʹʹǤͻȌ ͷȋʹͻǤͶȌ
    ͲǤͷʹʹͶ
    •‹ƒ ͳʹȋͳͳǤͲȌ ͲȋͲǤͲȌ
    ‡•–‘ˆ–Š‡™‘”Ž† ͷȋͶǤ͸Ȍ ͲȋͲǤͲȌ
    
    ‡•–”‡•’‘•‡–‘Žƒ•–’”‹‘”Ž‹‡‘ˆ–Š‡”ƒ’›ǦȋΨȌ
    ‘’Ž‡–‡”‡•’‘•‡ ͳȋͲǤͻȌ ͲȋͲǤͲȌ
    ƒ”–‹ƒŽ”‡•’‘•‡ ͳͳȋͳͲǤͳȌ ͳȋͷǤͻȌ
    –ƒ„Ž‡†‹•‡ƒ•‡ ʹͺȋʹͷǤ͹Ȍ ͷȋʹͻǤͶȌ
    ͲǤ͵ʹͲͶ
    ”‘‰”‡••‹˜‡†‹•‡ƒ•‡ Ͷ͵ȋ͵ͻǤͶȌ ͷȋʹͻǤͶȌ
    ‡˜ƒŽ—ƒ„Ž‡ ͲȋͲǤͲȌ ͳȋͷǤͻȌ
    ‘™Ȁ‘–ƒ’’Ž‹ ƒ„Ž‡Ȁ‘–†‘‡ ʹʹȋʹͲǤʹȌ ͷȋʹͻǤͶȌ
    ǣ‘–˜ƒ‹Žƒ„Ž‡ǡ ǣƒ•–‡”‘‘’‡”ƒ–‹˜‡ ‘Ž‘‰› ”‘—’Ǥ

    ƒˆ‡–›ƒ†ˆˆ‡ –‹˜‡‡••‡•—Ž–•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”KRAS ͳʹ


    —–ƒ–‹‘•
    a. Safety Results
    ƒ–ƒ”‡‰ƒ”†‹‰–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‹ ƒ ›‘ˆ̻ȋ•‘–‘”ƒ•‹„Ȍ–Š‡”ƒ’›™‡”‡’”‡•‡–‡†‹–Š‡
    ‘”‹‰‹ƒŽ†”—‰ƒ’’”‘˜ƒŽƒ†ƒ”‡•—ƒ”‹œ‡†‹–Š‡†”—‰Žƒ„‡ŽǤ‡ˆ‡”–‘–Š‡̻ȋ•‘–‘”ƒ•‹„Ȍ
    Žƒ„‡Žˆ‘”‘”‡‹ˆ‘”ƒ–‹‘Ǥ‘ƒ†˜‡”•‡‡˜‡–•™‡”‡”‡’‘”–‡†‹–Š‡ ‘†— –‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†‹‡•
    —•‡†–‘•—’’‘”––Š‡•‡ Žƒ‹•ƒ•–Š‡•‡‹˜‘Ž˜‡†”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ„ƒ‡†•’‡ ‹‡•‘Ž›Ǥ

    ͹͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    b. Effectiveness Results
    ‹Ǥ ‹ƒ–‹‡–•„› —ƒ”†ƒ–͵͸Ͳšˆ‘”KRAS ͳʹ—–ƒ–‹‘•
    Š‡‡ˆˆ‹ ƒ ›‘ˆ•‹‰Ž‡Ǧƒ‰‡–̻ȋ•‘–‘”ƒ•‹„Ȍ‹„‘–Š–Š‡’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘
    ’‘’—Žƒ–‹‘ȋ Ȍƒ†‹–Š‘•‡•—„Œ‡ –•’‘•‹–‹˜‡ˆ‘” ͳʹ„› —ƒ”†ƒ–͵͸Ͳš‹••Š‘™‹
    Table 55ǤŠ‡‘„•‡”˜‡†ȋ͵ͺΨǡͻͷΨ ʹ͹ΨȂͶͻΨȌ‹••‹‹Žƒ”–‘–Šƒ–ˆ‘”–Š‡ˆ—ŽŽ’”‹ƒ”›
    •‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ȋ ǡ͵͸ΨǡͻͷΨ ʹͺΨȂͶͷΨȌǤ

    Table 55. ORR in the gCEAS and FAS Populations Assessed by Independent Radiological Review
    Efficacy Parameter gCEAS (n = 77) FAS (n = 124)
    Objective Response Rate, N (%) ʹͻȋ͵ͺ  Ͷͷȋ͵͸ 
    (95%CI) ȋʹ͹ǡͶͻȌ ȋʹͺǡͶͷȌ
    ‘’Ž‡–‡‡•’‘•‡ǡȋΨȌ Ͳ Ͳ Ȍ ʹ ʹ Ȍ
    ƒ”–‹ƒŽ‡•’‘•‡ǡȋΨȌ ʹͻȋ͵ͺȌ Ͷ͵ȋ͵ͷȌ
    Duration of Response
    ‡†‹ƒƒǡ‘–Š•ȋ”ƒ‰‡Ȍ ͹ǤͳȋͳǤ͵ǡͺǤͶȌ ͳͲǤͲȋͳǤ͵ǡͳͳǤͳȌ
    ƒ–‹‡–™‹–Šη͸‘–Š•ǡΨ ͶʹΨ ͷͺΨ
    ƒ•–‹ƒ–‡†„›ƒ’ŽƒǦ‡‹‡”‡–Š‘†

    ‹‹Ǥ ‡•‹–‹˜‹–›ƒŽ›•‹•
    ‡•‹–‹˜‹–›ƒƒŽ›•‡•™‡”‡ ‘†— –‡†–‘‘†‡Ž–Š‡‹’ƒ –‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš Ϊ–‹••—‡Ȃ
    ’‘’—Žƒ–‹‘ƒ†’ƒ–‹‡–•™‹–Š‘—– —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•Ǥ
    ‡•‹–‹˜‹–›ƒŽ›•‹•ˆ‘”–Š‡”‡’”‡•‡–‡† —ƒ”†ƒ–͵͸Ͳš Ϊ‹••—‡Ȃ—„Œ‡ –‘’—Žƒ–‹‘
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•ƒ„‘˜‡†‡‘•–”ƒ–‡†•‘–‘”ƒ•‹„‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸Ͳš Ϊ
    –‹••—‡Ϊ•—„•‡–‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ••—„Œ‡ –•‹–Š‡‰‡
    ʹͲͳ͹ͲͷͶ͵ Ž‹‹ ƒŽ•–—†›™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘’‘•‹–‹˜‡–‹••—‡–‡•–‹‰ˆ‘”KRAS ͳʹǡ•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•™ƒ•ƒ••‡••‡†—•‹‰ƒ– Š‡†–‹••—‡ƒ†’Žƒ•ƒ•ƒ’Ž‡•ȋ’”‘ —”‡†ˆ”‘˜‡†‘”•ƒ†Ȁ‘”
    ‘–Š‡” Ž‹‹ ƒŽ–”‹ƒŽ•‘—” ‡•ƒ ‘”†‹‰–‘–Š‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ•‹‹Žƒ”–‘–Š‡‰‡ʹͲͳ͹ͲͷͶ͵
    Ž‹‹ ƒŽ•–—†›ȌǤ‡•‹–‹˜‹–›ƒƒŽ›•‹•‘†‡Ž‹‰‡ˆˆ‹ ƒ ›‹–Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš Ϊ‹–‡†‡†—•‡
    ’‘’—Žƒ–‹‘†‡‘•–”ƒ–‡•”‘„—•–‡••–‘–Š‡ ‘–”‹„—–‹‘‘ˆ–Š‡—”‡’”‡•‡–‡† —ƒ”†ƒ–͵͸Ͳš Ϊ
    –‹••—‡Ȃ•—„Œ‡ –•ǡ™‹–Š‡•–‹ƒ–‡†•Š‹‰ŠŽ›•‹‹Žƒ”–‘–Š‡‘„•‡”˜‡†ȋ Table 56˜•ǤTable 55ǡ
    ”‡•’‡ –‹˜‡Ž›Ȍ†—‡–‘–Š‡Š‹‰Š‘ˆ —ƒ”†ƒ–͵͸Ͳš”‡Žƒ–‹˜‡–‘–Š‡therascreenKRAS 
    ‹–—•‹‰–‹••—‡ǤŠ‡Ž‘™‡”Ž‹‹–‘ˆ–Š‡ͻͷΨ ˆ‘”–Š‡‡•–‹ƒ–‡†•ƒ ”‘••–Š‡‘†‡Ž‡†
    ‘†‹–‹‘•ȋʹ͹Ǥ͵ΨǡTable 56Ȍ‹•‰”‡ƒ–‡”–Šƒ–Š‡•‹œ‡Ǧƒ†Œ—•–‡†„‡ Šƒ”‘ˆʹʹΨǡ™Š‹ Š
    †‡‘•–”ƒ–‡••–ƒ–‹•–‹ ƒŽŽ›Ǧ•‹‰‹ˆ‹ ƒ–•‘–‘”ƒ•‹„‡ˆˆ‹ ƒ ›ƒ ”‘••–Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš
    ‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǡ‹””‡•’‡ –‹˜‡‘ˆ•‘–‘”ƒ•‹„‡ˆˆ‹ ƒ ›‹–Š‡‘†‡Ž‡† —ƒ”†ƒ–͵͸Ͳš Ϊ
    –‹••—‡Ȃ•—„Ǧ’‘’—Žƒ–‹‘Ǥ

    Table 56. Sensitivity Analysis for the Guardant360 CDx + Tissue– Population
    Guardant360 CDx+
     Intended Use Population
    ‡‹‰Š–‡†‘„Œ‡ –‹˜‡”‡•’‘•‡”ƒ–‡™‹–Š’‘•–—Žƒ–‡†‡“—ƒŽ–‘‘„•‡”˜‡†
    ˜‡”ƒ‰‡™‡‹‰Š–‡†ǦΨ ͵͹Ǥͷ
    ͻͷΨ  ȋʹ͹Ǥ͵ǡͶͺǤͳȌ
    
    ‡‹‰Š–‡†‘„Œ‡ –‹˜‡”‡•’‘•‡”ƒ–‡™‹–Š’‘•–—Žƒ–‡†‡“—ƒŽ–‘Ͳ
    ˜‡”ƒ‰‡™‡‹‰Š–‡†ǦΨ ͵͹Ǥͷ
    ͻͷΨ  ȋʹ͹Ǥ͵ǡͶͺǤͳȌ
    ͹͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ‡•‹–‹˜‹–›ƒŽ›•‹•ˆ‘” —„Œ‡ –•‹–Š‘—–ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš‡•—Ž–•
    Š‡ƒŒ‘”‹–›‘ˆ–Š‡•—„Œ‡ –•‹–Š‡’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ͳͳʹȀͳʹ͸ȋͺͺǤͻΨȌ
    ‡––Š‡ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‹ Ž—•‹‘ ”‹–‡”‹ƒȋ‰Ȍǡƒ†ͳͲͻȀͳʹ͸ȋͺ͸ǤͷΨȌ•—„Œ‡ –•‰‡‡”ƒ–‡†ƒ
    ˜ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–ȋ‰‘”‰ȂȌǤ‘‘†‡Ž–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ–Š‡ͳ͹•—„Œ‡ –•
    ™‹–Š‘—– —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•ǡ•‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†„ƒ•‡†‘ͳͲͲͲ•‹—Žƒ–‹‘•
    ‹’—–‹‰ —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•ˆ‘”•—„Œ‡ –•™‹–Š‘—–ƒ˜ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–‹–Š‡
    „”‹†‰‹‰•–—†›—•‹‰–Š‡ȋ —ƒ”†ƒ–͵͸ͲšΪȁ‹••—‡ΪȌ‘„•‡”˜‡†‹–Š‡ —ƒ”†ƒ–͵͸Ͳš
    ‡˜ƒŽ—ƒ„Ž‡ƒƒŽ›•‹••‡–ǤTable 57•Š‘™•–Šƒ––Š‡‘†‡Ž‡†ƒ˜‡”ƒ‰‡ȋ͵͸ΨǡͻͷΨ ͵ͶȂ͵ͺΨȌ
    ™‹–Š‹’—–ƒ–‹‘ˆ‘”–Š‡‹••‹‰’‘’—Žƒ–‹‘ȋ‰ǦȌ‹••‹‹Žƒ”–‘–Š‡‘„•‡”˜‡†‹–Š‡‰
    ȋ͵ͺΨǡͻͷΨ ʹ͹ΨȂͶͻΨȌǡ†‡‘•–”ƒ–‹‰–Šƒ––Š‡‘„•‡”˜‡†‹–Š‡ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‹•
    ”‘„—•––‘–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ‹••‹‰•—„Œ‡ –•Ǥ

    Table 57. Sensitivity Analysis with Imputation for Subjects Without Valid Guardant360 CDx
    Results
     Simulated gCEAS
    „Œ‡ –‹˜‡”‡•’‘•‡”ƒ–‡ȋȌ
    ˜‡”ƒ‰‡—„‡”‘ˆ‘˜‡”ƒŽŽ”‡•’‘†‡”•ȂȋΨȌ ͵ʹȋ͵ͷǤͺȌ
    ͻͷΨ  ȋ͵Ͷǡ͵ͺȌ

    ‹ƒ‰‘•–‹ –—†›‘ Ž—•‹‘•


    Š‡†‹ƒ‰‘•–‹ •–—†›‡––Š‡’”‡•’‡ ‹ˆ‹‡†ƒ ‡’–ƒ ‡ ”‹–‡”‹‘ƒ••‘ ‹ƒ–‡†™‹–Š‹–•’”‹ƒ”›‘„Œ‡ –‹˜‡Ǥ
    Ž‹‹ ƒŽŽ›”‡Ž‡˜ƒ–†”—‰‡ˆˆ‹ ƒ ›™ƒ•‡•–ƒ„Ž‹•Š‡†„›†‡‘•–”ƒ–‹‰–Šƒ––Š‡ˆ‘”•—„Œ‡ –•ˆ”‘–Š‡
    ’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘’‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”KRAS ͳʹ—–ƒ–‹‘•
    ȋ‰ǡ‘„•‡”˜‡†͵ͺΨǡͻͷΨ ʹ͹ΨȂͶͻΨȌ™ƒ••—’‡”‹‘”–‘–Š‡’”‡•’‡ ‹ˆ‹‡†„‡ Šƒ”‘ˆ
    ʹʹΨƒ†™ƒ•Š‹‰ŠŽ›•‹‹Žƒ”–‘–Šƒ–‘ˆ–Š‡–‘–ƒŽ’”‹ƒ”›•‘–‘”ƒ•‹„”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ȋ ǡ
    ‘„•‡”˜‡†͵͸ΨǡͻͷΨ ʹͺΨȂͶͷΨ Ǥ
    ‡•‹–‹˜‹–›ƒƒŽ›•‹•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšΪ–‹••—‡Ȃ’‘’—Žƒ–‹‘ƒ†‹’—–ƒ–‹‘ƒƒŽ›•‹•ˆ‘”•—„Œ‡ –•
    ™‹–Š‘—–˜ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•†‡‘•–”ƒ–‡†”‘„—•–‡••‘ˆ–Š‡‘„•‡”˜‡†–‘’‘–‡–‹ƒŽ
    ‡ˆˆ‡ –•ˆ”‘–Š‡•‡’‘’—Žƒ–‹‘•Ǥ
    —ƒ”†ƒ–͵͸Ͳšƒ†–Š‡therascreenKRAS ‹–—•‹‰–‹••—‡™‡”‡Š‹‰ŠŽ› ‘ ‘”†ƒ–‹–Š‡
    †‡–‡ –‹‘‘ˆKRAS ͳʹ—–ƒ–‹‘•Ǥ

    ͹ǤͷǤ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”ERBB2  –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†š‘ʹͲ


    •‡”–‹‘•Ȍ
     —‰ͲͳȋͺʹͲͳǦǦʹͲͶȌŽ‹‹ ƒŽ–—†›‡•‹‰
    Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›‹•ƒŠƒ•‡ʹǡ—Ž–‹ ‡–‡”ǡ‘’‡ǦŽƒ„‡ŽǡʹǦ ‘Š‘”–ǡ Ž‹‹ ƒŽ•–—†›‘ˆ
    ‹–”ƒ˜‡‘—•Ž›ƒ†‹‹•–‡”‡† ̺ȋˆƒǦ–”ƒ•–—œ—ƒ„†‡”—š–‡ ƒǦš‹Ȍ‹•—„Œ‡ –•™‹–Š
    —”‡•‡ –ƒ„Ž‡ƒ†Ȁ‘”‡–ƒ•–ƒ–‹ ǤŠ‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›’‘’—Žƒ–‹‘ ‘’”‹•‡•‘ˆ
    ERBB2ƒ –‹˜ƒ–‹‘—–ƒ–‹‘Ǧ’‘•‹–‹˜‡•—„Œ‡ –•ˆ”‘‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ•–—†›™Š‘•‡
    †‹•‡ƒ•‡’”‘‰”‡••‡†‘‘”ƒˆ–‡”•–ƒ†ƒ”†–Š‡”ƒ’›ƒ†™Š‘™‡”‡–”‡ƒ–‡†™‹–Šƒ–Ž‡ƒ•–‘‡†‘•‡‘ˆ
     Ǥƒ–‹‡–•™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘–Š‡’”‡•‡ ‡‘ˆERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†
    ‡š‘ʹͲ‹•‡”–‹‘•Ȍ„›–‹••—‡–‡•–‹‰Ǥ

    ͹ͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    —ƒ”†ƒ–͵͸Ͳš”‹†‰‹‰–—†›‡•‹‰ˆ‘”ERBB2 –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†š‘ʹͲ
    •‡”–‹‘•Ȍ
    ”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡•ˆ”‘ͺͻͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›•—„Œ‡ –•ˆ”‘‘Š‘”–ʹȋͺͻȀͻͳǡ
    ͻ͹ǤͺΨ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›’‘’—Žƒ–‹‘Ȍ™‡”‡–‡•–‡†™‹–Š —ƒ”†ƒ–͵͸ͲšǤŠ‡
    ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›†‹†‘–‹ Ž—†‡’ƒ–‹‡–•‡‰ƒ–‹˜‡ˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•
    ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍƒ†–Š‡”‡ˆ‘”‡†‹†‘–”‡’”‡•‡––Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡ǡ–‹••—‡Ǧ„ƒ•‡†
    Ǧ‡‰ƒ–‹˜‡ȋ —ƒ”†ƒ–͵͸ͲšΪǦȌ•—„‰”‘—’‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ
    ••— Šǡ•—’’Ž‡‡–ƒŽƒ– Š‡†–‹••—‡ƒ†’Žƒ•ƒ•ƒ’Ž‡•™‡”‡ ‘‡” ‹ƒŽŽ›’”‘ —”‡†ˆ”‘
    ˜‡†‘”•—•‹‰•—„Œ‡ –•ƒ’Ž‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ•‹‹Žƒ”–‘–Š‘•‡‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›ǡ
    ƒ†ƒ•‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ•’‡”ˆ‘”‡†–‘‡˜ƒŽ—ƒ–‡–Š‡’‘–‡–‹ƒŽ‹’ƒ –‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš Ϊ
    Ǧ’‘’—Žƒ–‹‘‘–Š‡‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ
    a. Clinical Bridging Study Inclusion and Exclusion Criteria
    ŽŽ•—„Œ‡ –•‹–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›’‘’—Žƒ–‹‘™‡”‡‹ Ž—†‡†‹–Š‡†‹ƒ‰‘•–‹ •–—†›
    ‡ˆˆ‹ ƒ › ‘Š‘”–‹ˆ–Š‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ„‡Ž‘™™‡”‡‡–Ǥ‹‹Žƒ”Ž›ǡƒŽŽ•—„Œ‡ –•‡‡–‹‰–Š‡•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†› ‘Š‘”–•‡Ž‡ –‹‘ ”‹–‡”‹ƒƒ”‡‹ Ž—†‡†Ǥ
    x Inclusion Criteria for Plasma Samples from the DS8201-A-U204 Clinical Study Efficacy Cohort
    o ƒ–Š‘Ž‘‰‹ ƒŽŽ›†‘ —‡–‡†—”‡•‡ –ƒ„Ž‡ƒ†Ȁ‘”‡–ƒ•–ƒ–‹ Ǥ
    o ƒ•”‡Žƒ’•‡†ˆ”‘‘”‹•”‡ˆ”ƒ –‘”›–‘•–ƒ†ƒ”†–”‡ƒ–‡–‘”ˆ‘”™Š‘‘•–ƒ†ƒ”†
    –”‡ƒ–‡–‹•ƒ˜ƒ‹Žƒ„Ž‡Ǥ
    o ‘ —‡–‡† ‘”‡“—‹˜ƒŽ‡–Žƒ„‘”ƒ–‘”›–‹••—‡–‡•–”‡•—Ž–†‡‘•–”ƒ–‹‰–Š‡’”‡•‡ ‡‘ˆ
    ƒ‡Ž‹‰‹„Ž‡ERBB2—–ƒ–‹‘Ǥ
    o ”‡•‡ ‡‘ˆƒ–Ž‡ƒ•–‘‡‡ƒ•—”ƒ„Ž‡Ž‡•‹‘ƒ••‡••‡†„›–Š‡‹˜‡•–‹‰ƒ–‘”„ƒ•‡†‘ 
    ˜‡”•‹‘ͳǤͳǤ
    x Inclusion Criteria for Guardant360 CDx Diagnostic Study Efficacy Cohort
    o —„Œ‡ –‡”‘ŽŽ‡†‹‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›™‹–Š‹ˆ‘”‡† ‘•‡–ˆ‘”
    „Ž‘‘†•ƒ’Ž‡•—•‡†ˆ‘”†‹ƒ‰‘•–‹ †‡˜‡Ž‘’‡–Ǥ
    o —„Œ‡ –•Šƒ†ƒ†‡“—ƒ–‡’”‡Ǧ–”‡ƒ–‡–’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘” —ƒ”†ƒ–͵͸Ͳš
    –‡•–‹‰Ǥ
    x Inclusion Criteria for Guardant360 CDx Diagnostic Study Sensitivity Analysis Prevalence Sub-
    Study
    o ƒ–Š‘Ž‘‰‹ ƒŽŽ›†‘ —‡–‡†ǡŽ‘ ƒŽŽ›ƒ†˜ƒ ‡†‘”‡–ƒ•–ƒ–‹ Ǥ
    o —„Œ‡ –—•–‡‹–Š‡”„‡’”‡˜‹‘—•Ž›—–”‡ƒ–‡†‘”Šƒ˜‡ƒ –‹˜‡†‹•‡ƒ•‡’”‘‰”‡••‹‘ƒ†™‡”‡
    ‘–”‡ ‡‹˜‹‰ƒ –‹˜‡ ƒ ‡”–Š‡”ƒ’›ƒ––Š‡–‹‡‘ˆ„Ž‘‘† ‘ŽŽ‡ –‹‘Ǥ
    o —„Œ‡ –•—•–’”‘˜‹†‡ƒ” Š‹˜‡†–—‘”–‹••—‡•ƒ’Ž‡•ȋ—•–ƒ‹‡†•Ž‹†‡•ƒ†Ȁ‘”ƒ 
    –‹••—‡„Ž‘  ‘ŽŽ‡ –‡†™‹–Š‹ͷ›‡ƒ”•‘ˆ–Š‡ƒ– Š‡†’Žƒ•ƒ•ƒ’Ž‡Ȍ™‹–Š•—ˆˆ‹ ‹‡––—‘”
    ‘–‡–ƒ†“—ƒ–‹–›ˆ‘”–‡•–‹‰ƒ•†‡ˆ‹‡†„›–Š‡ ‡–”ƒŽ–‡•–‹‰Žƒ„‘”ƒ–‘”›”‡“—‹”‡‡–•Ǥ
    o —„Œ‡ –—•–’”‘˜‹†‡’Žƒ•ƒ•ƒ’Ž‡ƒ˜ƒ‹Žƒ„Ž‡ˆ‘” —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰Ǥ
    b. Clinical Endpoints
    Š‡ Ž‹‹ ƒŽ‡†’‘‹–—•‡†–‘ƒ••‡•• ‡ˆˆ‹ ƒ ›‹–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›’”‹ƒ”›
    ‘„Œ‡ –‹˜‡™ƒ•‘„Œ‡ –‹˜‡”‡•’‘•‡ȋȌ„› ˜‡”•‹‘ͳǤͳƒ•ƒ••‡••‡†„›‹†‡’‡†‡– ‡–”ƒŽ
    ”‡˜‹‡™ȋ ȌǤ

    ͹ͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    c. Diagnostic Objective and Endpoints
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡‘ˆ–Š‡ Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‹•–‘†‡‘•–”ƒ–‡–Š‡ Ž‹‹ ƒŽ˜ƒŽ‹†‹–›‘ˆ
    —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆ•—„Œ‡ –•™‹–ŠERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†
    ‡š‘ʹͲ‹•‡”–‹‘•Ȍ†‡–‡ –‡†‹’Žƒ•ƒˆ‘”–”‡ƒ–‡–™‹–Š ǤŠ‡’”‹ƒ”›‡†’‘‹–‹•„›
     ˜‡”•‹‘ͳǤͳƒ•ƒ••‡••‡†„› Ǥ•‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ• ‘†— –‡†–‘‘†‡Ž–Š‡‹’ƒ –‘ˆ
    –Š‡ —ƒ”†ƒ–͵͸ͲšΪǦ’‘’—Žƒ–‹‘Ǥ
     ‘—–ƒ„‹Ž‹–›‘ˆ–Š‡‘Š‘”–ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”ERBB2
     –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†š‘ʹͲ •‡”–‹‘• 
    Š‡ —ƒ”†ƒ–͵͸Ͳš Ž‹‹ ƒŽ„”‹†‰‹‰•–—†›‹ Ž—†‡†ͺͻȋ‰Ǣͻ͹ǤͺΨȌ‘ˆ–Š‡ͻͳ•—„Œ‡ –•ȋ Ȍ
    ‡”‘ŽŽ‡†‹‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶȋFigure 9ȌǤˆ–Š‡•‡ǡͺͳ•—„Œ‡ –•ȋ‰ǡͺͻΨȌ™‡”‡
    –‡•–‡†’‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšƒ†™‡”‡‹ Ž—†‡†‹–Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹••‡–ȋ‰Ȍǡ
    ™Š‹Ž‡ͺȋ‰ǦǡͺǤͺΨȌ™‡”‡‡‰ƒ–‹˜‡Ǥˆ–Š‡ͻͳ•—„Œ‡ –•‡”‘ŽŽ‡†‹–Š‡ͺʹͲͳǦǦʹͲͶǡʹȋ‰ǡʹǤʹΨȌ
    ™‡”‡‘––‡•–‡†„‡ ƒ—•‡’Žƒ•ƒ™ƒ•—ƒ˜ƒ‹Žƒ„Ž‡Ǥ‘•ƒ’Ž‡•ˆƒ‹Ž‡†–‡•–‹‰„› —ƒ”†ƒ–͵͸ͲšǤ

    Figure 9. Guardant360 CDx ERBB2 Activating Mutation Bridging Study Efficacy Analysis Subject
    Accountability and Analysis Set Definitions
    ‘–‡ǣŽ‹‹ ƒŽ‡ˆˆ‹ ƒ ›•—„‰”‘—’ȋ‰Ȍ•Šƒ†‡†‹‰”‡‡ǤŽ‹‹ ƒŽ‡ˆˆ‹ ƒ › ‘’ƒ”ƒ–‘”•—„‰”‘—’••Šƒ†‡†‹‰”ƒ›Ǥ
    Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›•‡–‹ Ž—†‡†ͳ͸ͻ•—„Œ‡ –•™‹–Šƒ– Š‡†’Žƒ•ƒƒ†
    –‹••—‡ȋFigure 10ȌǤˆ–Š‘•‡ͳ͸ͻǡͷͺ•—„Œ‡ –•ȋ͵ͶǤ͵ΨȌˆƒ‹Ž‡†‘”™‡”‡‘––‡•–‡†„›‡‹–Š‡” —ƒ”†ƒ–͵͸Ͳ
    šƒ†Ȁ‘”–‹••—‡Ǧ„ƒ•‡†–‡•–‹‰ǤŠ‹•‹• ‘’”‹•‡†‘ˆ͵͸•ƒ’Ž‡•–Šƒ–ˆƒ‹Ž‡†–‡•–‹‰„—–Šƒ˜‡
    —ƒ”†ƒ–͵͸Ͳš”‡•—Ž–•Ǣͳ͹•ƒ’Ž‡•–Šƒ–ˆƒ‹Ž‡† —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰„—–Šƒ˜‡”‡•—Ž–•Ǣʹ
    •ƒ’Ž‡•–Šƒ–ˆƒ‹Ž‡†„‘–Šƒ† —ƒ”†ƒ–͵͸Ͳš–‡•–‹‰Ǣƒ†͵•ƒ’Ž‡•–Šƒ–™‡”‡—ƒ„Ž‡–‘„‡
    –‡•–‡†„› —ƒ”†ƒ–͵͸Ͳšƒ†Ȁ‘”ǤŠ‹•”‡•—Ž–‡†‹ͳͳͳ•—„Œ‡ –•™‹–Š˜ƒŽ‹† —ƒ”†ƒ–͵͸Ͳš
    ƒ†–‹••—‡”‡•—Ž–•Ǥˆ–Š‡•‡ǡ‘‡•—„Œ‡ –™ƒ• —ƒ”†ƒ–͵͸Ͳš ΪΪǡ‘•—„Œ‡ –•™‡”‡
    —ƒ”†ƒ–͵͸ͲšΪǦ‘” —ƒ”†ƒ–͵͸ͲšǦΪǡƒ†ͳͳͲ•—„Œ‡ –•™‡”‡ —ƒ”†ƒ–͵͸ͲšǦǦǤ

    ͺͲ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Figure 10. Guardant360 CDx ERBB2 Sensitivity Analysis Prevalence Sub-Study Subject
    Accountability
    ‘–‡ǣ••ƒ›ƒ‰”‡‡‡–•—„‰”‘—’ȋȌ•Šƒ†‡†‹‰”‡‡Ǥ

    ‘ ‘”†ƒ ‡‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†‹••—‡‡•–‹‰


    ‘ ‘”†ƒ ‡„‡–™‡‡ —ƒ”†ƒ–͵͸Ͳšƒ†–‹••—‡Ǧ„ƒ•‡†–‡•–‹‰—•‹‰ƒ– Š‡†’Žƒ•ƒƒ†
    –‹••—‡•ƒ’Ž‡•ˆ”‘‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›ǡƒŽ‘‰™‹–Š–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•
    ’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›‰”‘—’ǡ‹••Š‘™‹Table 58„‡Ž‘™ǤŠ‹Ž‡ƒŽŽ•ƒ’Ž‡•ˆ”‘–Š‡’”‹ƒ”›
     ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡’‘•‹–‹˜‡ˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ
    ‹•‡”–‹‘•Ȍ„›–‹••—‡–‡•–‹‰ƒ•ƒ ‘†‹–‹‘‘ˆ–Š‡‹”‡”‘ŽŽ‡–‹–Š‡ Ž‹‹ ƒŽ•–—†›ǡ–Š‡•‡•‹–‹˜‹–›
    ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›•—„Œ‡ –•™‡”‡”‡ ”—‹–‡†‹ƒ‡ˆˆ‘”––‘”‡’”‡•‡––Š‡ERBB2Ǧ‡‰ƒ–‹˜‡
    ’‘’—Žƒ–‹‘Ǥ
    ‘”–Š‡ ‘ ‘”†ƒ ‡ƒƒŽ›•‹•ȋTable 58Ȍǡ™Š‡ƒ••‡••‹‰–Š‡’‘•‹–‹˜‡’‡” ‡–ƒ‰”‡‡‡–ȋȌǡ–Š‡
    ͺͻ–‹••—‡Ǧ’‘•‹–‹˜‡•—„Œ‡ –•ˆ”‘–Š‡’”‹ƒ”› ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡‹ Ž—†‡†Ǥ 
    ƒ††‹–‹‘ǡ–Š‡ͳͳͳ•—„Œ‡ –•ˆ”‘–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•’”‡˜ƒŽ‡ ‡•—„Ǧ•–—†›™‹–Š˜ƒŽ‹†”‡•—Ž–•™‡”‡
    ‹ Ž—†‡†ƒ•†‡• ”‹„‡†‹Figure 10ƒ„‘˜‡Ǥ

    Table 58. Concordance Between Guardant360 CDx and Tissue-based CTA


    CTA Positive, n CTA Negative, n Total
    —ƒ”†ƒ–͵͸Ͳš‘•‹–‹˜‡ǡ ͺʹ Ͳ ͺʹ
    —ƒ”†ƒ–͵͸Ͳš‡‰ƒ–‹˜‡ǡ ͺ ͳͳͲ ͳͳͺ
    ‘–ƒŽ ͻͲ ͳͳͲ ʹͲͲ
    ‘•‹–‹˜‡‡” ‡–‰”‡‡‡–ȏͻͷΨ ȏͳȐȐ ͻͳǤͳΨȋͺʹȀͻͲȌȏͺ͵ǤʹΨǦͻ͸ǤͳΨȐ
    ‡‰ƒ–‹˜‡‡” ‡–‰”‡‡‡–ȏͻͷΨ ȏͳȐȐ ͳͲͲΨȋͳͳͲȀͳͳͲȌȏͻ͸Ǥ͹ΨǦͳͲͲǤͲΨȐ
    ȏͳȐŠ‡ͻͷΨ ‹• ƒŽ —Žƒ–‡†—•‹‰–Š‡šƒ –ȋŽ‘’’‡”Ǧ‡ƒ”•‘Ȍ‡–Š‘†Ǥ

    –—†›‘’—Žƒ–‹‘‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡Ž‹‹ ƒŽƒ”ƒ‡–‡”•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ


    ”‹†‰‹‰–—†›ˆ‘”ERBB2 –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†š‘ʹͲ •‡”–‹‘•Ȍ
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ•—„Œ‡ –•‡”‘ŽŽ‡†‹‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦ
    ʹͲͶ Ž‹‹ ƒŽ•–—†›™‡”‡ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡–‘–Š‡†‹ƒ‰‘•–‹ •–—†›’‘’—Žƒ–‹‘•ƒ•†‡ˆ‹‡†„›
    —ƒ”†ƒ–͵͸ͲšǤ

    ͺͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ••Š‘™‹Table 59ƒ†Table 60ǡ–Š‡†‹ƒ‰‘•–‹ •–—†›‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ȋ‰Ȍ†‡‘‰”ƒ’Š‹ •
    ƒ†–Š‡„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ • Ž‘•‡Ž›”‡•‡„Ž‡–Š‘•‡‘ˆ–Š‡‘˜‡”ƒŽŽͺʹͲͳǦǦʹͲͶ
     —‰Ͳͳ†‹ƒ‰‘•–‹  Ž‹‹ ƒŽ•–—†›’‘’—Žƒ–‹‘ȋ ȌǤ‡‘‰”ƒ’Š‹ ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ
    Šƒ”ƒ –‡”‹•–‹ •‘ˆ–Š‡ƒ††‹–‹‘ƒŽ•—„Ǧ‰”‘—’’‘’—Žƒ–‹‘•™‡”‡ƒŽ•‘ ‘’ƒ”ƒ„Ž‡–‘ ƒ†‰Ǥ

    Table 59. Baseline Demographics of the Clinical Effectiveness Analysis FAS and Sub-Groups
    gCEAS gAS- gAS gAS-Unk Total (FAS)
    N=81 N=8 N=89 N=2 N=91
    Age (years)
     ͺͳ ͺ ͺͻ ʹ ͻͳ
    ‡ƒ ͷͻǤͺ ͸ͷǤͻ ͸ͲǤͶ ͷͷǤͷ ͸ͲǤ͵
     ͳͳǤʹ͸ ͳͶǤ͹Ͷ ͳͳǤ͸Ͷ ʹͺǤͻͻ ͳͳǤͻͶ
    ‡†‹ƒ ͸Ͳ ͸ʹǤͷ ͸Ͳ ͷͷǤͷ ͸Ͳ
    ‹ǡƒš ʹͻǡ͹ͻ Ͷͺǡͺͺ ʹͻǡͺͺ ͵ͷǡ͹͸ ʹͻǡͺͺ
    Sex – n (%)
    ‡ƒŽ‡ ͷʹȋ͸ͶǤʹ  ͸ȋ͹ͷǤͲȌ ͷͺȋ͸ͷǤʹ  ʹȋͳͲͲǤͲȌ ͸Ͳȋ͸ͷǤͻ 
    ƒŽ‡ ʹͻȋ͵ͷǤͺ  ʹȋʹͷǤͲȌ ͵ͳȋ͵ͶǤͺ  Ͳ ͵ͳȋ͵ͶǤͳ 
    Race – n (%)
    Š‹–‡ ͵ͶȋͶʹǤͲ  ͷȋ͸ʹǤͷȌ ͵ͻȋͶ͵Ǥͺ  ͳȋͷͲǤͲȌ ͶͲȋͶͶǤͲ 
    Žƒ ‘”ˆ”‹ ƒ‡”‹ ƒ ͳȋͳǤʹȌ Ͳ ͳȋͳǤͳȌ Ͳ ͳȋͳǤͳȌ
    •‹ƒ ʹͺȋ͵ͶǤ͸  ͵ȋ͵͹ǤͷȌ ͵ͳȋ͵ͶǤͺ  Ͳ ͵ͳȋ͵ͶǤͳ 
    ‡”‹ ƒ †‹ƒ‘”Žƒ•ƒ
    Ͳ Ͳ Ͳ Ͳ Ͳ
    ƒ–‹˜‡
    ƒ–‹˜‡ ƒ™ƒ‹‹ƒ‘”–Š‡”ƒ ‹ˆ‹ 
    Ͳ Ͳ Ͳ Ͳ Ͳ
    •Žƒ†‡”
    ‹•’ƒ‹  Ͳ Ͳ Ͳ Ͳ Ͳ
    –Š‡” ͳͺȋʹʹǤʹ  Ͳ ͳͺȋʹͲǤʹ  ͳȋͷͲǤͲȌ ͳͻȋʹͲǤͻ 
    ‹••‹‰Ȁ‘™ Ͳ Ͳ Ͳ Ͳ Ͳ
    Ethnicity – n (%)
    ‹•’ƒ‹ ‘”ƒ–‹‘ ʹȋʹǤͷȌ Ͳ ʹȋʹǤʹȌ Ͳ ʹȋʹǤʹȌ
    ‘– ‹•’ƒ‹ ‘”ƒ–‹‘ ͸Ͳȋ͹ͶǤͳ  ͹ȋͺ͹ǤͷȌ ͸͹ȋ͹ͷǤ͵  ͳȋͷͲǤͲȌ ͸ͺȋ͹ͶǤ͹ 
    ‘–’’Ž‹ ƒ„Ž‡ ͳͻȋʹ͵Ǥͷ  ͳȋͳʹǤͷȌ ʹͲȋʹʹǤͷ  ͳȋͷͲǤͲȌ ʹͳȋʹ͵Ǥͳ 
    ECOG Score – n (%)
    Ͳ ʹͲȋʹͶǤ͹  ʹȋʹͷǤͲȌ ʹʹȋʹͶǤ͹  ͳȋͷͲǤͲȌ ʹ͵ȋʹͷǤ͵ 
    ͳ ͸ͳȋ͹ͷǤ͵  ͸ȋ͹ͷǤͲȌ ͸͹ȋ͹ͷǤ͵  ͳȋͷͲǤͲȌ ͸ͺȋ͹ͶǤ͹ 
    αƒŽŽ•—„Œ‡ –•‹‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›Ǣ‰αƒŽŽ•—„Œ‡ –•ˆ”‘–Š‡ –‡•–‡†™‹–Š
    —ƒ”†ƒ–͵͸ͲšǢ‰ǦαŽŽ•—„Œ‡ –•‹–Š‡‰™Š‘–‡•–‡†‡‰ƒ–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•
    ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•ȌǢ‰αƒŽŽ•—„Œ‡ –•‹–Š‡‰™Š‘–‡•–‡†’‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ERBB2
    ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘• ȌǢ‰αƒŽŽ•—„Œ‡ –•ˆ”‘–Š‡ ‘––‡•–‡†„› —ƒ”†ƒ–͵͸ͲšǤ

    Table 60. Baseline Clinical Characteristics of the Clinical Effectiveness Analysis FAS and Sub-
    Groups
    gCEAS gAS- gAS gNT Total (FAS)
    N=81 N=8 N=89 N=2 N=91
    Histology – n (%)
    †‡‘ ƒ” ‹‘ƒ ͺͳȋͳͲͲǤͲȌ ͺȋͳͲͲǤͲȌ ͺͻȋͳͲͲǤͲȌ ʹȋͳͲͲǤͲȌ ͻͳȋͳͲͲǤͲȌ
    ƒ”‰‡‡ŽŽ Ͳ Ͳ Ͳ Ͳ Ͳ
    –Š‡” Ͳ Ͳ Ͳ Ͳ Ͳ
    Tumor Stage at Study Entry – n (%)
    Ǧ  Ͳ Ͳ Ͳ Ͳ Ͳ
     ͳȋͳǤʹȌ ͳȋͳʹǤͷȌ ʹȋʹǤʹȌ Ͳ ʹȋʹǤʹȌ
    ͺʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    gCEAS gAS- gAS gNT Total (FAS)
    N=81 N=8 N=89 N=2 N=91
     ʹȋʹǤͷȌ Ͳ ʹȋʹǤʹȌ Ͳ ʹȋʹǤʹȌ
     ͳȋͳǤʹȌ Ͳ ͳȋͳǤͳȌ Ͳ ͳȋͳǤͳȌ
     ͳͺȋʹʹǤʹȌ ͳȋͳʹǤͷȌ ͳͻȋʹͳǤ͵Ȍ ͳȋͷͲǤͲȌ ʹͲȋʹʹǤͲȌ
     ͳͻȋʹ͵Ǥͷ  ͵ȋ͵͹ǤͷȌ ʹʹȋʹͶǤ͹  ͳȋͷͲǤͲȌ ʹ͵ȋʹͷǤ͵ 
     ͶͲȋͶͻǤͶ  ͵ȋ͵͹ǤͷȌ Ͷ͵ȋͶͺǤ͵  Ͳ Ͷ͵ȋͶ͹Ǥ͵ 
    αƒŽŽ•—„Œ‡ –•‹‘Š‘”–ʹ‘ˆ–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›Ǣ‰αƒŽŽ•—„Œ‡ –•ˆ”‘–Š‡ –‡•–‡†™‹–Š
    —ƒ”†ƒ–͵͸ͲšǢ‰ǦαŽŽ•—„Œ‡ –•‹–Š‡‰™Š‘–‡•–‡†‡‰ƒ–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•
    ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•ȌǢ‰αƒŽŽ•—„Œ‡ –•‹–Š‡‰™Š‘–‡•–‡†’‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ERBB2
    ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•ȌǢ‰αƒŽŽ•—„Œ‡ –•ˆ”‘–Š‡ ‘––‡•–‡†„› —ƒ”†ƒ–͵͸ͲšǤ

    ƒˆ‡–›ƒ†ˆˆ‡ –‹˜‡‡••‡•—Ž–•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”ERBB2


     –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†š‘ʹͲ •‡”–‹‘• 
    a. Safety Results
    Š‡•ƒˆ‡–›‘ˆ ™ƒ•‡˜ƒŽ—ƒ–‡†ƒ––™‘†‘•‡Ž‡˜‡Ž•ǣ͸ǤͶ‰Ȁ‰ȋ Ǧ—‰ͲͳǡͺʹͲͳǦǦ
    ʹͲͶȌƒ†ͷǤͶ‰Ȁ‰ȋ Ǧ—‰ͲʹǡͺʹͲͳǦǦʹͲ͸ȌǤ ‹•„‡‹‰ƒ’’”‘˜‡†ƒ––Š‡
    Ž‘™‡”†‘•‡ȋͷǤͶ‰Ȁ‰Ȍ†—‡–‘‹ ”‡ƒ•‡†”ƒ–‡•‘ˆ –‡”•–‹–‹ƒŽ—‰‹•‡ƒ•‡ƒ†’‡—‘‹–‹•ƒ––Š‡
    Š‹‰Š‡”†‘•‡Ǥ†˜‡”•‡‡˜‡–•‘„•‡”˜‡†™‹–Š–Š‡Š‹‰Š‡”†‘•‡ƒ”‡—”‡Žƒ–‡†–‘ —ƒ”†ƒ–͵͸ͲšǤ
    ƒ–ƒ”‡‰ƒ”†‹‰–Š‡•ƒˆ‡–›‘ˆ –Š‡”ƒ’›ƒ”‡’”‡•‡–‡†‹–Š‡‘”‹‰‹ƒŽ†”—‰ƒ’’”‘˜ƒŽǤ‡ˆ‡”–‘
    –Š‡ Žƒ„‡Žˆ‘”‘”‡‹ˆ‘”ƒ–‹‘Ǥ‘ƒ†˜‡”•‡‡˜‡–•™‡”‡”‡’‘”–‡†‹–Š‡ ‘†— –‘ˆ–Š‡
    †‹ƒ‰‘•–‹ •–—†‹‡•—•‡†–‘•—’’‘”––Š‡•‡ Žƒ‹•ƒ•–Š‡•‡‹˜‘Ž˜‡†”‡–”‘•’‡ –‹˜‡–‡•–‹‰‘ˆ„ƒ‡†
    •’‡ ‹‡•‘Ž›Ǥ
    b. Effectiveness Results
    ‹Ǥ ‹ƒ–‹‡–•„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ERBB2 –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†š‘ʹͲ
    •‡”–‹‘•Ȍ
    Š‡‡ˆˆ‹ ƒ ›‘ˆˆƒǦ–”ƒ•–—œ—ƒ„†‡”—š–‡ ƒǦš‹ȋ  ̺Ȍ™ƒ•‡˜ƒŽ—ƒ–‡†‹ͺʹͲͳǦǦʹͲͶ
     —‰ͲͳǡαͻͳȌƒ†ͺʹͲͳǦǦʹͲ͸ȋ —‰ͲʹǡαͷʹȌ•–—†‹‡•ǤŠ‡‡ˆˆ‹ ƒ ›‘ˆ
     ‹„‘–Š•–—†›’‘’—Žƒ–‹‘•ȋ —‰Ͳͳƒ† —‰ͲʹȌƒ†•—„Œ‡ –•‹–Š‡
    †‹ƒ‰‘•–‹ •–—†›’‘•‹–‹˜‡ˆ‘”ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ„›
    —ƒ”†ƒ–͵͸Ͳšȋ‰Ȍ‹••Š‘™‹Table 61ǤŠ‡‘„•‡”˜‡†‰ȋͷͺǤͲΨǡͻͷΨ Ͷ͸ǤͷΨ
    Ǧ͸ͺǤͻΨȌ„ƒ•‡†‘–Š‡ —‰Ͳͳ•–—†›’‘’—Žƒ–‹‘‹••‹‹Žƒ”–‘–Š‡ȋͷ͹Ǥ͹ΨǡͻͷΨ ǣ
    Ͷ͵ǤʹΨǦ͹ͳǤ͵ΨȌˆ”‘–Š‡ ‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ȋ —‰ͲʹȌǤŠ‡Ž‘™‡”Ž‹‹–‘ˆ–Š‡
    ͻͷΨ ‡š ‡‡†•–Š‡„‡ Šƒ”‘ˆ͵ͲΨˆ”‘–Š‡ͺʹͲͳǦǦʹͲͶƒ†ͺʹͲͳǦǦʹͲ͸
    Ž‹‹ ƒŽ•–—†‹‡•ǤŠ‡†—”ƒ–‹‘‘ˆ”‡•’‘•‡ȋȌˆ‘” —ƒ”†ƒ–͵͸Ͳ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘
    ȋ‰Ȍ™ƒ•ͻǤʹͷ‘–Š•ȋͻͷΨ ǣͷǤ͹ǡͳͺǤʹ Ǥ

    Table 61. ORR in the gCEAS and ENHERTU Study Populations Assessed by Independent Central
    Review
    DESTINY Lung 01 *DESTINY Lung 02
    gCEAS (n=81) (n=91) - 6.4 mg/kg (n=52)- 5.4 mg/kg
    „Œ‡ –‹˜‡‡•’‘•‡ƒ–‡ǡȋΨ  Ͷ͹ȋͷͺǤͲ  ͷͲȋͷͶǤͻ  ͵Ͳȋͷ͹Ǥ͹ 
    ȋͻͷΨ  ȋͶ͸Ǥͷǡ͸ͺǤͻȌ ȋͶͶǤʹǡ͸ͷǤͶȌ ȋͶ͵Ǥʹǡ͹ͳǤ͵Ȍ
    ‘’Ž‡–‡”‡•’‘•‡ȋȌ ͳȋͳǤʹȌ ͳȋͳǤͳȌ ͳȋͳǤͻȌ
    ƒ”–‹ƒŽ”‡•’‘•‡ȋ  Ͷ͸ȋͷ͸Ǥͺ  Ͷͻȋͷ͵Ǥͺ  ʹͻȋͷͷǤͺ 

    ͺ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    DESTINY Lung 01 *DESTINY Lung 02
    gCEAS (n=81) (n=91) - 6.4 mg/kg (n=52)- 5.4 mg/kg
    —”ƒ–‹‘‘ˆ‡•’‘•‡ȋȌ
    ‡†‹ƒƒǡ‘–Š•ȋͻͷΨ Ȍ ͻǤ͵ȋͷǤ͹ǡͳͺǤʹȌ ͻǤ͵ȋͷǤ͹ǡͳͶǤ͹Ȍ ͺǤ͹ȋ͹ǤͳǡȌ
    ȗŠ‹•‹•–Š‡’”‹ƒ”›‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ˆ‘”–Š‡ƒ’’”‘˜ƒŽ‘ˆˆƒǦ–”ƒ•–—œ—ƒ„†‡”—š–‡ ƒǦš‹ȋ  ̺ȌǤƒ•–‹ƒ–‡†„›
    –Š‡ƒ’ŽƒǦ‡‹‡”‡–Š‘†Ǥᐑ–‡•–‹ƒ„Ž‡ǡ α ‘ˆ‹†‡ ‡‹–‡”˜ƒŽ
    Š‡ͻͷΨ ‹• ƒŽ —Žƒ–‡†—•‹‰–Š‡šƒ –ȋŽ‘’’‡”Ǧ‡ƒ”•‘Ȍ‡–Š‘†Ǥ

    ‹‹Ǥ ‡•‹–‹˜‹–›ƒŽ›•‹•
    •‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ• ‘†— –‡†–‘‘†‡Ž–Š‡‹’ƒ –‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš ΪǦ
    ’‘’—Žƒ–‹‘‘‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ
    ‡•‹–‹˜‹–›ƒŽ›•‹•ˆ‘”–Š‡”‡’”‡•‡–‡† —ƒ”†ƒ–͵͸Ͳš ΪǦ—„Œ‡ –‘’—Žƒ–‹‘
    Š‡’”‹ƒ”›‘„Œ‡ –‹˜‡ƒƒŽ›•‹•†‡• ”‹„‡†ƒ„‘˜‡†‡‘•–”ƒ–‡† ‡ˆˆ‹ ƒ ›‹–Š‡
    —ƒ”†ƒ–͵͸ͲšΪΪ•—„•‡–‘ˆ–Š‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘Ǥ••—„Œ‡ –•‹
    –Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›™‡”‡‡”‘ŽŽ‡†„ƒ•‡†‘’‘•‹–‹˜‡–‹••—‡–‡•–‹‰ˆ‘”ERBB2
    ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍǡƒ•‡•‹–‹˜‹–›ƒƒŽ›•‹•™ƒ•ƒ••‡••‡†—•‹‰
    ƒ– Š‡†–‹••—‡ƒ†’Žƒ•ƒ•ƒ’Ž‡•ȋ’”‘ —”‡†ˆ”‘˜‡†‘”•ƒ ‘”†‹‰–‘–Š‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ
    •‹‹Žƒ”–‘–Š‡ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›ȌǤŠ‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•‘†‡Ž‹‰‡ˆˆ‹ ƒ ›‹–Š‡
    ‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘†‡‘•–”ƒ–‡•”‘„—•–‡••–‘–Š‡ ‘–”‹„—–‹‘‘ˆ
    –Š‡—”‡’”‡•‡–‡† —ƒ”†ƒ–͵͸ͲšΪǦ•—„Œ‡ –•ǡ™‹–Š‡•–‹ƒ–‡†•Š‹‰ŠŽ›•‹‹Žƒ”–‘–Š‡
    ‘„•‡”˜‡†ȋTable 61˜•ǤTable 62Ȍ†—‡–‘–Š‡Š‹‰ŠȋͳͲͲΨȌ‘ˆ —ƒ”†ƒ–͵͸Ͳš”‡Žƒ–‹˜‡–‘
    –‹••—‡–‡•–‹‰ǤŠ‡Ž‘™‡”Ž‹‹–‘ˆ–Š‡ͻͷΨ ˆ‘”–Š‡‡•–‹ƒ–‡†•ƒ ”‘••–Š‡‘†‡Ž‡† ‘†‹–‹‘•
    ȋTable 62Ȍ‹•‰”‡ƒ–‡”–Šƒ–Š‡„‡ Šƒ”‘ˆ͵ͲΨ‹–Š‡ Ž‹‹ ƒŽ•–—†›ǡ™Š‹ Š†‡‘•–”ƒ–‡•
     ‡ˆˆ‹ ƒ ›ƒ ”‘••–Š‡‡–‹”‡ —ƒ”†ƒ–͵͸Ͳš‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǡ‹””‡•’‡ –‹˜‡‘ˆ
    ‡ˆˆ‹ ƒ ›‹–Š‡‘†‡Ž‡† —ƒ”†ƒ–͵͸ͲšΪǦ’‘’—Žƒ–‹‘Ǥ

    Table 62. Sensitivity Analysis for the Guardant360 CDx + CTA- Population
    1% ERBB2 Prevalence, Simulated 2% ERBB2 Prevalence, Simulated
    Assumed Effect in CDx+/CTA- ORR in CDx+/CTA- (95% CI) ORR in CDx+/CTA- (95% CI)
    ͳͲͲΨέ„•‡”˜‡†‹šΪȀΪ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ
    ͹ͷΨέ„•‡”˜‡†‹šΪȀΪ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ
    ͷͲΨέ„•‡”˜‡†‹šΪȀΪ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ
    ʹͷΨέ„•‡”˜‡†‹šΪȀΪ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ
    ͲΨέ„•‡”˜‡†‹šΪȀΪ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ ͲǤͷͺȋͲǤͶ͹ǡͲǤ͸ͺȌ
    ‘‹–‡•–‹ƒ–‡ǡ˜ƒ”‹ƒ ‡•ƒ† ‘ˆ‹†‡ ‡‹–‡”˜ƒŽ•ƒ”‡ˆ”‘„‘‘–•–”ƒ’’‹‰™‹–Šƒ•‡‡†‘ˆͳʹ͵Ͷͷƒ†ͳͲǡͲͲͲ”‡’Ž‹ ƒ–‡•Ǥ

    ‹ƒ‰‘•–‹ –—†›‘ Ž—•‹‘•


    Š‡†‹ƒ‰‘•–‹ •–—†›‡––Š‡’”‡•’‡ ‹ˆ‹‡†ƒ ‡’–ƒ ‡ ”‹–‡”‹‘ƒ••‘ ‹ƒ–‡†™‹–Š‹–•’”‹ƒ”›‘„Œ‡ –‹˜‡Ǥ
    Ž‹‹ ƒŽŽ›”‡Ž‡˜ƒ–†”—‰‡ˆˆ‹ ƒ ›™ƒ•‡•–ƒ„Ž‹•Š‡†„›†‡‘•–”ƒ–‹‰–Šƒ––Š‡Ǥˆ‘”•—„Œ‡ –•ˆ”‘–Š‡
    ͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›’‘’—Žƒ–‹‘’‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ERBB2ƒ –‹˜ƒ–‹‰
    —–ƒ–‹‘•ȋ‰ǡ‘„•‡”˜‡†ͷͺǤͲΨǡͻͷΨ Ͷ͸ǤͷΨǦ͸ͺǤͻΨȌ‡š ‡‡†‡†–Š‡’”‡•’‡ ‹ˆ‹‡†
    „‡ Šƒ”‘ˆ͵ͲΨƒ†™ƒ•Š‹‰ŠŽ›•‹‹Žƒ”–‘–Šƒ–‘ˆ–Š‡–‘–ƒŽͺʹͲͳǦǦʹͲͶ Ž‹‹ ƒŽ•–—†›
    ’‘’—Žƒ–‹‘ȋ ǡ‘„•‡”˜‡†ͷͶǤͻΨǡͻͷΨ ͶͶǤʹΨǦ͸ͷǤͶΨȌǤ
    ‡•‹–‹˜‹–›ƒƒŽ›•‹•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšΪǦ’‘’—Žƒ–‹‘ǡ†‡‘•–”ƒ–‡†”‘„—•–‡••‘ˆ–Š‡
    ‘„•‡”˜‡†–‘’‘–‡–‹ƒŽ‡ˆˆ‡ –ˆ”‘–Š‹•—‡˜ƒŽ—ƒ–‡†’‘’—Žƒ–‹‘Ǥ††‹–‹‘ƒŽŽ›ǡ —ƒ”†ƒ–͵͸Ͳš

    ͺͶ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    ƒ† ‘’ƒ”ƒ–‘”–‹••—‡–‡•–‹‰™‡”‡Š‹‰ŠŽ› ‘ ‘”†ƒ–ȋͻͳǤͳΨǢͳͲͲΨȌ‹–Š‡†‡–‡ –‹‘‘ˆ
    ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•ȌǤ
    Š—•ǡ †‡‘•–”ƒ–‡† Ž‹‹ ƒŽŽ›‡ƒ‹‰ˆ—Ž‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸Ͳš Ϊ‹–‡†‡†—•‡
    ’‘’—Žƒ–‹‘™Š‹ Š‹• ‘’ƒ”ƒ„Ž‡–‘–Šƒ–‘„•‡”˜‡†‹–Š‡ •‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ǤŠ‹•
    •—’’‘”–•–Š‡ Ž‹‹ ƒŽ˜ƒŽ‹†‹–›‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ’ƒ–‹‡–•™‹–Š™Š‘•‡
    –—‘”•Šƒ˜‡ERBB2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘•ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ†‡–‡ –‡†‹’Žƒ•ƒˆ‘”
     –Š‡”ƒ’›Ǥ

    ͹Ǥ͸Ǥ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ–—†›ˆ‘”ESR1—–ƒ–‹‘•


    ͳͻͲͳǦ͵ͲͺȏȋͲ͵͹͹ͺͻ͵ͳȌȐŽ‹‹ ƒŽ–—†›‡•‹‰
    Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ•–—†›‹•ƒ‹–‡”ƒ–‹‘ƒŽǡ—Ž–‹ ‡–‡”ǡ”ƒ†‘‹œ‡†ǡ‘’‡ǦŽƒ„‡Žǡƒ –‹˜‡Ǧ
    ‘–”‘ŽŽ‡†ǡ‡˜‡–Ǧ†”‹˜‡ǡŠƒ•‡͵ Ž‹‹ ƒŽ•–—†› ‘’ƒ”‹‰–Š‡‡ˆˆ‹ ƒ ›ƒ†•ƒˆ‡–›‘ˆ̻
    ‡Žƒ ‡•–”ƒ–Ȍ –‘–Š‡‘’–‹‘•‘ˆˆ—Ž˜‡•–”ƒ–‘”ƒƒ”‘ƒ–ƒ•‡‹Š‹„‹–‘”ȋ Ȍ‹’‘•–Ǧ‡‘’ƒ—•ƒŽ
    ™‘‡ƒ†‡™‹–ŠΪȀ ʹǦ‡–ƒ•–ƒ–‹ „”‡ƒ•– ƒ ‡”ȋȌǤŽ‹‰‹„Ž‡•—„Œ‡ –•™‡”‡”ƒ†‘‹œ‡†
    ‹ƒͳǣͳ”ƒ–‹‘–‘‡‹–Š‡”̻ȋ‡Žƒ ‡•–”ƒ–Ȍ‘”ƒ†•–”ƒ–‹ˆ‹‡†„›—–ƒ–‹‘•–ƒ–—•‘ˆESR1—•‹‰
    —ƒ”†ƒ–͵͸Ͳšƒ†‘–Š‡” ”‹–‡”‹ƒ†‡• ”‹„‡†‹–Š‡ Ž‹‹ ƒŽ•–—†›’”‘–‘ ‘ŽǤ
    —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ–—†›‡•‹‰ˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•
    ‘†‡‘•–”ƒ–‡–Š‡ Ž‹‹ ƒŽ˜ƒŽ‹†‹–›‘ˆ —ƒ”†ƒ–͵͸Ͳšˆ‘”–Š‡•‡Ž‡ –‹‘‘ˆΪȀ ʹǦ’ƒ–‹‡–•
    ™‹–ŠESR1‹••‡•‡—–ƒ–‹‘•ˆ‘”–”‡ƒ–‡–™‹–Š̻ȋ‡Žƒ ‡•–”ƒ–Ȍǡ–Š‡’”‹ƒ”›†‹ƒ‰‘•–‹ 
    •–—†›‘„Œ‡ –‹˜‡ȋ Ȍ™ƒ•ƒ••‡••‡†„› ‘’ƒ”‹‰–Š‡‡ˆˆ‹ ƒ ›‘ˆ•‹‰Ž‡Ǧƒ‰‡–̻ȋ‡Žƒ ‡•–”ƒ–Ȍ
    ”‡Žƒ–‹˜‡–‘‹•—„Œ‡ –•’‘•‹–‹˜‡ˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸ͲšǤ—„Œ‡ –•ˆ”‘
    –Š‡’”‹ƒ”›ͳͻͲͳǦ͵Ͳͺ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘’‘•‹–‹˜‡ˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•„›
    —ƒ”†ƒ–͵͸Ͳš™‡”‡‹ Ž—†‡†‹–Š‡†‹ƒ‰‘•–‹ •–—†›’”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ › ‘Š‘”–
    c. Clinical Study Inclusion and Exclusion Criteria
    —„Œ‡ –•‹–Š‡’”‹ƒ”›ͳͻͲͳǦ͵Ͳͺ”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘™‡”‡‹ Ž—†‡†‹–Š‡†‹ƒ‰‘•–‹ •–—†›
    ‡ˆˆ‹ ƒ › ‘Š‘”–‹ˆ–Š‡•‡Ž‡ –‹‘ ”‹–‡”‹ƒ„‡Ž‘™™‡”‡‡–Ǥ
    o ƒŽ‡‘”’‘•–‡‘’ƒ—•ƒŽˆ‡ƒŽ‡
    o ‹•–‘Ž‘‰‹ ƒŽŽ›Ǧ‘” ›–‘Ž‘‰‹ ƒŽŽ›Ǧ’”‘˜‡ƒ†‡‘ ƒ” ‹‘ƒ‘ˆ–Š‡„”‡ƒ•–™‹–Š‡˜‹†‡ ‡‘ˆ
    ‡‹–Š‡”Ž‘ ƒŽŽ›ƒ†˜ƒ ‡††‹•‡ƒ•‡‘–ƒ‡ƒ„Ž‡–‘”‡•‡ –‹‘‘””ƒ†‹ƒ–‹‘–Š‡”ƒ’›™‹–Š
    —”ƒ–‹˜‡‹–‡–‘”‡–ƒ•–ƒ–‹ †‹•‡ƒ•‡‘–ƒ‡ƒ„Ž‡–‘ —”ƒ–‹˜‡–Š‡”ƒ’›
    o —•–„‡ƒ’’”‘’”‹ƒ–‡ ƒ†‹†ƒ–‡•ˆ‘”‡†‘ ”‹‡‘‘–Š‡”ƒ’›
    o —•–Šƒ˜‡Ϊƒ† ʹǦ–—‘”•–ƒ–—• ‘ˆ‹”‡†’‡”Ž‘ ƒŽŽƒ„‘”ƒ–‘”›–‡•–‹‰
    o —•–Šƒ˜‡’”‡˜‹‘—•Ž›”‡ ‡‹˜‡†ƒ–Ž‡ƒ•–ͳƒ†‘‘”‡–ŠƒʹŽ‹‡•‘ˆ‡†‘ ”‹‡–Š‡”ƒ’›ǡ
    ‡‹–Š‡”ƒ‘‘–Š‡”ƒ’›‘”ƒ•ƒ ‘„‹ƒ–‹‘–Š‡”ƒ’›™‹–Šƒ‘–Š‡”ƒ‰‡–Ǣ’”‹‘”–”‡ƒ–‡–
    ™‹–ŠƒͶȀ͸‹Š‹„‹–‘”‹ ‘„‹ƒ–‹‘™‹–Š‡‹–Š‡”ˆ—Ž˜‡•–”ƒ–‘”ƒ Ǣƒ†‘‘”‡–Šƒ–
    ͳŽ‹‡‘ˆ ›–‘–‘š‹  Š‡‘–Š‡”ƒ’›‹–Š‡•‡––‹‰
    o ‡ƒ•—”ƒ„Ž‡†‹•‡ƒ•‡‘”‘Ǧ‡ƒ•—”ƒ„Ž‡„‘‡Ǧ‘Ž›†‹•‡ƒ•‡Ǥ

    d. Follow-up Schedule
    Š‡ —ƒ”†ƒ–͵͸Ͳš†‹ƒ‰‘•–‹ •–—†›‹˜‘Ž˜‡†‘Ž›–‡•–‹‰ƒ†ƒƒŽ›•‹•‘ˆ’Žƒ•ƒ•ƒ’Ž‡•Ǣƒ••— Šǡ
    ‘ƒ††‹–‹‘ƒŽ’ƒ–‹‡–ˆ‘ŽŽ‘™Ǧ—’™ƒ• ‘†— –‡†‹”‡‰ƒ”†–‘–Š‡†‹ƒ‰‘•–‹ •–—†›Ǥ

    ͺͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    e. Clinical Endpoints
    Š‡ Ž‹‹ ƒŽ‡†’‘‹–—•‡†–‘ƒ••‡••̻ȋ‡Žƒ ‡•–”ƒ–Ȍ‡ˆˆ‹ ƒ ›‹–Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ
    •–—†›’”‹ƒ”›‘„Œ‡ –‹˜‡™ƒ• „› ˜‡”•‹‘ͳǤͳƒ•ƒ••‡••‡†„›‹†‡’‡†‡– ‡–”ƒŽ”‡˜‹‡™
    ȋ Ȍ‘”†‡ƒ–Šˆ”‘ƒ› ƒ—•‡Ǥ
    f. Diagnostic Objective and Endpoints
    Š‡†‹ƒ‰‘•–‹ •–—†›‘„Œ‡ –‹˜‡™ƒ•–‘†‡‘•–”ƒ–‡–Š‡•ƒˆ‡–›ƒ†‡ˆˆ‡ –‹˜‡‡••‘ˆ —ƒ”†ƒ–͵͸Ͳš
    ƒ•ƒ ‘’ƒ‹‘†‹ƒ‰‘•–‹ –‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘‘ˆ„”‡ƒ•– ƒ ‡”’ƒ–‹‡–•™‹–ŠESR1‹••‡•‡
    —–ƒ–‹‘•ˆ‘”̻ȋ‡Žƒ ‡•–”ƒ–Ȍ–Š‡”ƒ’›™ƒ•ƒ ‘Ǧ†‡˜‡Ž‘’‡–•–—†›—–‹Ž‹œ‹‰’Žƒ•ƒ•ƒ’Ž‡•
    ƒ† Ž‹‹ ƒŽ‘—– ‘‡†ƒ–ƒˆ”‘–Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ•–—†›Ǥ
    Š‡‘„Œ‡ –‹˜‡™ƒ•ƒ••‡••‡†„› ‘’ƒ”‹‰–Š‡‡ˆˆ‹ ƒ ›‘ˆ̻ȋ‡Žƒ ‡•–”ƒ–Ȍ–‘–Šƒ–‘ˆ
    –Š‡”ƒ’›ȋˆ—Ž˜‡•–”ƒ–‘”ƒƒ”‘ƒ–ƒ•‡‹Š‹„‹–‘”Ȍ‹’ƒ–‹‡–•–Šƒ–ƒ”‡’‘•‹–‹˜‡ˆ‘”ESR1‹••‡•‡
    —–ƒ–‹‘•„› —ƒ”†ƒ–͵͸ͲšǤŠ‡’”‹ƒ”›‡†’‘‹–‹•–Š‡•ƒ‡ƒ•–Šƒ–—•‡†ˆ‘”–Š‡ Ž‹‹ ƒŽ•–—†›ǡ
     „› ͳǤͳƒ•ƒ••‡••‡†„› Ǥ
     ‘—–ƒ„‹Ž‹–›‘ˆ–Š‡‘Š‘”–ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•
    Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ•–—†›”‡‰‹•–”ƒ–‹‘’‘’—Žƒ–‹‘ȋ Ȍ‹ Ž—†‡†Ͷ͹ͺ•—„Œ‡ –•ǡʹʹͺ‘ˆ™Š‹ Š
    Šƒ†ESR1‹••‡•‡—–ƒ–‹‘•†‡–‡ –‡†„› —ƒ”†ƒ–͵͸Ͳšȋ ESR1Ǧ—–Ȍǡƒ†ʹͶͻ‘ˆ™Š‹ Š†‹†‘–
    Šƒ˜‡ƒESR1‹••‡•‡—–ƒ–‹‘†‡–‡ –‡†„› —ƒ”†ƒ–͵͸ͲšȋESR1Ǧ—–Ǧ†ȌȋFigure 11ȌǤ‘–‡ǡ‘‡
    •—„Œ‡ –™ƒ•‡”‘ŽŽ‡†‹–‘–Š‡”‡‰‹•–”ƒ–‹‘ƒŽ’‘’—Žƒ–‹‘„ƒ•‡†‘ƒ•— ‡••ˆ—Ž —ƒ”†ƒ–͵͸Ͳ–‡•–
    ”‡•—Ž–„—–™ƒ•‡š Ž—†‡†ˆ”‘–Š‡†‹ƒ‰‘•–‹ •–—†›‡ˆˆ‹ ƒ ›ƒƒŽ›•‹•†—‡–‘ˆƒ‹Ž—”‡‘”‡ƒƒŽ›•‹•
    ™‹–Š–Š‡ˆ‹ƒŽ —ƒ”†ƒ–͵͸Ͳš„‹‘‹ˆ‘”ƒ–‹ ••‘ˆ–™ƒ”‡Ǥ

    
    Figure 11. Guardant360 CDx ESR1 Mutation Efficacy Analysis Patient Accountability and
    Analysis Set Definitions
    ‘–‡ǣ”‹ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ȋESR1Ǧ—–Ȍ•Šƒ†‡†‹‰”‡‡Ǥš Ž—†‡†‘”•‡ ‘†ƒ”› Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘•
    ȋESR1Ǧ—–Ǧ†ƒ† Ȍ•Šƒ†‡†‹‰”ƒ›Ǥ

    –—†›‘’—Žƒ–‹‘‡‘‰”ƒ’Š‹ •ƒ†ƒ•‡Ž‹‡Ž‹‹ ƒŽƒ”ƒ‡–‡”•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ


    –—†›ˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•
    ‡‘‰”ƒ’Š‹ •ƒ†„ƒ•‡Ž‹‡ Ž‹‹ ƒŽ Šƒ”ƒ –‡”‹•–‹ •‘ˆ•—„Œ‡ –•‡”‘ŽŽ‡†‹–Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ
    •–—†›™‡”‡ ƒ–‡‰‘”‹œ‡†”‡Žƒ–‹˜‡–‘–Š‡†‹ƒ‰‘•–‹ •–—†›’‘’—Žƒ–‹‘•ƒ•†‡ˆ‹‡†„› —ƒ”†ƒ–͵͸Ͳš
    ”‡•—Ž–•Ǥ
    ••Š‘™‹Table 63ƒ†Table 64ǡ–Š‡†‹ƒ‰‘•–‹ •–—†›’”‹ƒ”›‡ˆˆ‹ ƒ ›’‘’—Žƒ–‹‘ȋ ESR1Ǧ—–Ȍ
    ƒ†–Š‡ESR1Ǧ—–Ǧ†’‘’—Žƒ–‹‘ƒ”‡™‡ŽŽ„ƒŽƒ ‡†ǤŠ‡̻ȋ‡Žƒ ‡•–”ƒ–Ȍƒ†–”‡ƒ–‡–
    ƒ”•ƒ”‡ƒŽ•‘™‡ŽŽ„ƒŽƒ ‡†Ǥ

    ͺ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Table 63. Baseline Demographics of the FAS and Sub-Groups
     Elacestrant SOC Total
     ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd
    Analysis set: 115 124 113 125 228 249
         
    Age (years),
    115 (0) 124 (0) 113 (0) 125 (0) 228 (0) 249 (0)
    n (missing)
    ‡ƒ ͸ʹǤ͹ ͸ʹǤͶ ͸ʹǤͲ ͸ͶǤͶ ͸ʹǤͶ ͸͵ǤͶ
     ͳʹǤʹͷ ͳͳǤͻͳ ͳͳǤ͹Ͷ ͳͲǤͲ͵ ͳͳǤͻͺ ͳͳǤͲ͵
    ‡†‹ƒ ͸ͶǤͲ ͸͵ǤͲ ͸͵ǤͲ ͸ͶǤͲ ͸͵ǤͲ ͸ͶǤͲ
    ‹ ʹͺ ʹͶ ͵ʹ Ͷͳ ʹͺ ʹͶ
    ƒš ͺͻ ͺͶ ͺ͵ ͺʹ ͺͻ ͺͶ
    
    Age (years), n (%),
    115 (0) 124 (0) 113 (0) 125 (0) 228 (0) 249 (0)
    n (missing)
    εαͳͺǦδͷͲ ͳͷȋͳ͵ǤͲ  ͳͺȋͳͶǤͷ  ͳͻȋͳ͸Ǥͺ  ͳͲȋͺǤͲȌ ͵ͶȋͳͶǤͻ  ʹͺȋͳͳǤʹ 
    εαͷͲǦδ͸ͷ Ͷ͹ȋͶͲǤͻ  ͷͷȋͶͶǤͶ  Ͷ͵ȋ͵ͺǤͳ  ͷͷȋͶͶǤͲ  ͻͲȋ͵ͻǤͷ  ͳͳͲȋͶͶǤʹȌ
    εα͸ͷǦδ͹ͷ ͵͸ȋ͵ͳǤ͵  ʹͺȋʹʹǤ͸  ͵Ͷȋ͵ͲǤͳ  ͵ͳȋʹͶǤͺ  ͹Ͳȋ͵ͲǤ͹  ͷͻȋʹ͵Ǥ͹ 
    εα͹ͷ ͳ͹ȋͳͶǤͺȌ ʹ͵ȋͳͺǤͷȌ ͳ͹ȋͳͷǤͲȌ ʹͻȋʹ͵ǤʹȌ ͵ͶȋͳͶǤͻȌ ͷʹȋʹͲǤͻȌ
    δ͸ͷ ͸ʹȋͷ͵ǤͻȌ ͹͵ȋͷͺǤͻȌ ͸ʹȋͷͶǤͻȌ ͸ͷȋͷʹǤͲȌ ͳʹͶȋͷͶǤͶȌ ͳ͵ͺȋͷͷǤͶȌ
    εα͸ͷ ͷ͵ȋͶ͸Ǥͳ  ͷͳȋͶͳǤͳ  ͷͳȋͶͷǤͳ  ͸ͲȋͶͺǤͲ  ͳͲͶȋͶͷǤ͸Ȍ ͳͳͳȋͶͶǤ͸Ȍ
    
    Race n (%)[1],
    94 (21) 96 (28) 92 (21) 102 (23) 186 (42) 198 (51)
    n (missing)
    ‡”‹ ƒ †‹ƒ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    ‘”Žƒ•ƒƒ–‹˜‡
    •‹ƒ ͷȋͷǤ͵Ȍ ͳͳȋͳͳǤͷ  ͺȋͺǤ͹Ȍ ͺȋ͹ǤͺȌ ͳ͵ȋ͹ǤͲȌ ͳͻȋͻǤ͸Ȍ
    Žƒ ‘”ˆ”‹ ƒ ͶȋͶǤ͵Ȍ ͳȋͳǤͲȌ ͶȋͶǤ͵Ȍ ͵ȋʹǤͻȌ ͺȋͶǤ͵Ȍ ͶȋʹǤͲȌ
    ‡”‹ ƒ
    ƒ–‹˜‡ ƒ™ƒ‹‹ƒ‘” ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ
    –Š‡”ƒ ‹ˆ‹ 
    •Žƒ†‡”
    Š‹–‡Ȁƒ— ƒ•‹ƒ ͺͶȋͺͻǤͶ  ͺͶȋͺ͹Ǥͷ  ͺͲȋͺ͹ǤͲ  ͻͲȋͺͺǤʹ  ͳ͸ͶȋͺͺǤʹȌ ͳ͹Ͷȋͺ͹ǤͻȌ
    –Š‡” ͳȋͳǤͳȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͳȋͳǤͲȌ ͳȋͲǤͷȌ ͳȋͲǤͷȌ
    
    Gender n (%),
    115(0) 124 (0) 113 (0) 125 (0) 228 (0) 249 (0)
    n (missing)
    ƒŽ‡ ͲȋͲǤͲȌ ͸ȋͶǤͺȌ Ͳ Ͳ  ͳȋͲǤͺȌ ͲȋͲǤͲȌ ͹ȋʹǤͺȌ
    ‡ƒŽ‡ ͳͳͷȋͳͲͲǤͲȌ ͳͳͺȋͻͷǤʹȌ ͳͳ͵ȋͳͲͲǤͲȌ ͳʹͶȋͻͻǤʹȌ ʹʹͺȋͳͲͲǤͲȌ ʹͶʹȋͻ͹ǤʹȌ
    
    Ethnicity, n (%),
    115(0) 124 (0) 113 (0) 125 (0) 228 (0) 249 (0)
    n (missing)
    ‹•’ƒ‹ ‘”ƒ–‹‘ ͳͲȋͺǤ͹Ȍ ͻȋ͹Ǥ͵Ȍ ͳͲȋͺǤͺȌ ͺȋ͸ǤͶȌ ʹͲȋͺǤͺ  ͳ͹ȋ͸ǤͺȌ
    ‘Ǧ ‹•’ƒ‹ ‘” ͻʹȋͺͲǤͲ  ͳͲʹȋͺʹǤ͵Ȍ ͺͺȋ͹͹Ǥͻ  ͳͲʹȋͺͳǤ͸Ȍ ͳͺͲȋ͹ͺǤͻȌ ʹͲͶȋͺͳǤͻȌ
    ƒ–‹‘
    ‘™ ͳ͵ȋͳͳǤ͵Ȍ ͳ͵ȋͳͲǤͷȌ ͳͷȋͳ͵Ǥ͵Ȍ ͳͷȋͳʹǤͲȌ ʹͺȋͳʹǤ͵Ȍ ʹͺȋͳͳǤʹȌ
    
    Height, (cm),
    113(2) 123(1) 112(1) 124(1) 225(3) 247(2)
    n (missing)
    ‡ƒ ͳ͸ͳǤͻͺ ͳ͸ʹǤ͸ʹ ͳ͸ͲǤ͸ͷ ͳ͸ͳǤʹͶ ͳ͸ͳǤʹ͹ ͳ͸ͳǤͻ͵
     ͹ǤͶͷͶ ͺǤʹ͵Ͳ ͸ǤͶͺʹ ͹Ǥ͹Ͷ͵ ͸Ǥͻͻͺ ͺǤͲͲ͵
    ‡†‹ƒ ͳ͸ͲǤͲͲ ͳ͸ͳǤͲͲ ͳ͸ͲǤͶͲ ͳ͸ʹǤͲͲ ͳ͸ͲǤ͵Ͳ ͳ͸ʹǤͲͲ
    ‹ ͳͶ͵ǤͲ ͳͶͶǤͺ ͳͶͷǤͲ ͳͶʹǤͲ ͳͶ͵ǤͲ ͳͶʹǤͲ
    ƒš ͳͺ͵ǤͲ ͳͻͲǤͲ ͳ͹͵ǤͲ ͳͺ͵ǤͲ ͳͺ͵ǤͲ ͳͻͲǤͲ
    

    ͺ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
     Elacestrant SOC Total
     ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd
    Weight (kg),
    115(0) 124(0) 113 (0) 125 (0) 228(0) 249(0)
    n (missing)
    ‡ƒ ͹͵ǤͶͳ ͹ʹǤͲͶ ͹ͳǤͺ͹ ͹ʹǤͺ͵ ͹ʹǤ͸ͷ ͹ʹǤͶ͵
     ͳ͹ǤͳͶͷ ͳͷǤͲͻʹ ͳ͸ǤͶͷͷ ͳ͸ǤͶͶ͵ ͳ͸Ǥ͹ͺ͹ ͳͷǤ͹ͷͺ
    ‡†‹ƒ ͸ͻǤͲͲ ͹ͲǤͲͲ ͸ͻǤͳͲ ͹ʹǤͲͲ ͸ͻǤͲͷ ͹ͲǤͶͷ
    ‹ ͶʹǤͲ ͶͶǤͲ ͶͶǤͲ ͶʹǤͲ ͶʹǤͲ ͶʹǤͲ
    ƒš ͳ͵ͷǤͲ ͳʹͷǤ͹ ͳʹͶǤͲ ͳ͵ʹǤ͵ ͳ͵ͷǤͲ ͳ͵ʹǤ͵
    
    BMI (kg/m2),
    113(2) 123 (1) 112 (1) 124 (1) 225 (3) 247 (2)
    n (missing)
    ‡ƒ ʹͺǤͲ͹ ʹ͹Ǥͳ͵ ʹ͹Ǥͺͺ ʹ͹Ǥͻͷ ʹ͹Ǥͻ͹ ʹ͹Ǥͷͷ
     ͸ǤͲͷͺ ͶǤͻͲͳ ͸ǤͲͳʹ ͷǤ͹ͷʹ ͸ǤͲʹ͵ ͷǤ͵ͷͲ
    ‡†‹ƒ ʹ͸Ǥ͵Ͳ ʹ͹ǤͲ͵ ʹ͹ǤͶͳ ʹ͸Ǥ͹ͷ ʹ͸ǤͶͺ ʹ͸Ǥͺͷ
    ‹ ͳ͹Ǥͷ ͳͺǤʹ ͳ͸Ǥͻ ͳ͸Ǥͷ ͳ͸Ǥͻ ͳ͸Ǥͷ
    ƒš ͷʹǤ͹ ͶͲǤͻ ͶͷǤͳ Ͷ͹Ǥͺ ͷʹǤ͹ Ͷ͹Ǥͺ
    
    ECOG Performance
    Status n (%), 115 (0) 124 (0) 113 (0) 125 (0) 228 (0) 249 (0)
    n (missing)
    Ͳ ͸͹ȋͷͺǤ͵Ȍ ͹͸ȋ͸ͳǤ͵Ȍ ͸ʹȋͷͶǤͻȌ ͹͵ȋͷͺǤͶȌ ͳʹͻȋͷ͸Ǥ͸Ȍ ͳͶͻȋͷͻǤͺȌ
    ͳ ͶͺȋͶͳǤ͹  Ͷͺȋ͵ͺǤ͹  ͷͳȋͶͷǤͳ  ͷͳȋͶͲǤͺ  ͻͻȋͶ͵ǤͶ  ͻͻȋ͵ͻǤͺ 
    εͳ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͲȋͲǤͲȌ ͳȋͲǤͺȌ ͲȋͲǤͲȌ ͳȋͲǤͶȌ
    α–ƒ†ƒ”†‡˜‹ƒ–‹‘ǡ‹α‹‹—ǡƒšαƒš‹—ǡ ᑆ›ƒ•• †‡šǡ ვ–‡”‘‘’‡”ƒ–‹˜‡ ‘Ž‘‰›
    ”‘—’
    ȏͳȐ—„Œ‡ –•ƒ›•‡Ž‡ –‘”‡–Šƒͳ”ƒ ‡Ǥ

    Table 64. Baseline Clinical Characteristics of the FAS and Sub-Groups


    Elacestrant SOC Total
    ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd
    Years Since Initial Diagnosis
    ȋ‹••‹‰Ȍ ͳͳͷ ͲȌ ͳʹͶ ͲȌ ͳͳ͵ȋͲȌ ͳʹͷȋͲȌ ʹʹͺ ͲȌ ʹͶͻ ͲȌ
    ‡ƒ ͹ǤͶͻ ͺǤ͸͵ ͺǤͶͳ ͺǤͻͲ ͹Ǥͻͷ ͺǤ͹͹
     ͸Ǥͷʹ͹ ͸Ǥ͵͹ʹ ͸Ǥͻͺͷ ͹Ǥ͹Ͷʹ ͸Ǥ͹ͷͻ ͹ǤͲͺͲ
    ‡†‹ƒ ͶǤͻʹ ͸Ǥ͹͸ ͷǤ͹ͷ ͸ǤͶʹ ͷǤͶʹ ͸Ǥ͸͵
    ‹ ͲǤʹ ͲǤ͹ ͲǤͻ ͲǤͷ ͲǤʹ ͲǤͷ
    ƒš ʹͺǤͶ ͵ʹǤʹ ͵ͳǤͲ ͶͲǤͳ ͵ͳǤͲ ͶͲǤͳ
    Stage at Initial Diagnosis, n (%)
     ͳͷ ȋͳ͵ǤͲȌ ʹͲ ȋͳ͸ǤͳȌ ͳͳ ȋͻǤ͹Ȍ ͳͺ ȋͳͶǤͶȌ ʹ͸ ȋͳͳǤͶȌ ͵ͺ ȋͳͷǤ͵Ȍ
     ʹ͹ ȋʹ͵ǤͷȌ ͷ͵ ȋͶʹǤ͹Ȍ ͵ͻ ȋ͵ͶǤͷ  Ͷʹ ȋ͵͵Ǥ͸  ͸͸ ȋʹͺǤͻȌ ͻͷ ȋ͵ͺǤʹȌ
     ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ Ͳ ȋͲǤͲȌ
     ͷ ȋͶǤ͵Ȍ ͳͶ ȋͳͳǤ͵Ȍ ͸ ȋͷǤ͵Ȍ ͳͶ ȋͳͳǤʹȌ ͳͳ ȋͶǤͺȌ ʹͺ ȋͳͳǤʹȌ
     Ͷ ȋ͵ǤͷȌ ͵ ȋʹǤͶȌ Ͳ ȋͲǤͲȌ ͵ ȋʹǤͶȌ Ͷ ȋͳǤͺȌ ͸ ȋʹǤͶȌ
     Ͷ ȋ͵ǤͷȌ ͹ ȋͷǤ͸Ȍ ͸ ȋͷǤ͵Ȍ ͳ ȋͲǤͺȌ ͳͲ ȋͶǤͶȌ ͺ ȋ͵ǤʹȌ
     Ͷʹ ȋ͵͸ǤͷȌ ʹͲ ȋͳ͸ǤͳȌ ͵ͺ ȋ͵͵Ǥ͸  ͵ͺ ȋ͵ͲǤͶ  ͺͲ ȋ͵ͷǤͳȌ ͷͺ ȋʹ͵Ǥ͵Ȍ
    ‘™ ͳ͹ ȋͳͶǤͺȌ ͹ ȋͷǤ͸Ȍ ͳʹ ȋͳͲǤ͸Ȍ ͻ ȋ͹ǤʹȌ ʹͻ ȋͳʹǤ͹Ȍ ͳ͸ ȋ͸ǤͶȌ
    T Stage at Initial Diagnosis, n (%)
    ͳ ͳͺ ȋͳͷǤ͹Ȍ ʹͻ ȋʹ͵ǤͶȌ ʹͲ ȋͳ͹Ǥ͹  ʹ͵ ȋͳͺǤͶ  ͵ͺ ȋͳ͸Ǥ͹Ȍ ͷʹ ȋʹͲǤͻȌ
    ʹ ʹͻ ȋʹͷǤʹȌ Ͷͺ ȋ͵ͺǤ͹Ȍ ͶͲ ȋ͵ͷǤͶ  Ͷͻ ȋ͵ͻǤʹ  ͸ͻ ȋ͵ͲǤ͵Ȍ ͻ͹ ȋ͵ͻǤͲȌ
    ͵ ͳ͵ ȋͳͳǤ͵Ȍ ͳͺ ȋͳͶǤͷȌ ͸ ȋͷǤ͵Ȍ ͳͳ ȋͺǤͺȌ ͳͻ ͺ Ǥ͵Ȍ ʹͻ ȋͳͳǤ͸Ȍ
    Ͷ ͳͳ ȋͻǤ͸Ȍ ͹ ȋͷǤ͸Ȍ ͳͲ ȋͺǤͺȌ ͳ͵ ȋͳͲǤͶȌ ʹͳ ȋͻǤʹȌ ʹͲ ȋͺǤͲȌ
    ‘™ ͵ ȋʹǤ͸Ȍ ʹ ȋͳǤ͸Ȍ ͷ ȋͶǤͶȌ ʹ ȋͳǤ͸Ȍ ͺ ȋ͵ǤͷȌ Ͷ ȋͳǤ͸Ȍ

    ͺͺ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Elacestrant SOC Total
    ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd
    N Stage at Initial Diagnosis, n (%)
    Ͳ ͳ͸ ȋͳ͵ǤͻȌ ͵ͷ ȋʹͺǤʹ  ͳͷ ȋͳ͵Ǥ͵  ͵ͺ ȋ͵ͲǤͶ  ͵ͳ ȋͳ͵Ǥ͸Ȍ ͹͵ ȋʹͻǤ͵Ȍ
    ͳ ͵Ͷ ȋʹͻǤ͸Ȍ Ͷͷ ȋ͵͸Ǥ͵  ͵͹ ȋ͵ʹǤ͹  ͵ͳ ȋʹͶǤͺ  ͹ͳ ȋ͵ͳǤͳȌ ͹͸ ȋ͵ͲǤͷȌ
    ʹ ͳͶ ȋͳʹǤʹȌ ͳͶ ȋͳͳǤ͵  ͳͲ ȋͺǤͺȌ ͳͶ ȋͳͳǤʹ  ʹͶ ȋͳͲǤͷȌ ʹͺ ȋͳͳǤʹȌ
    ͵ ͻ ȋ͹ǤͺȌ ͹ ȋͷǤ͸Ȍ ͳͳ ȋͻǤ͹Ȍ ͳͳ ͺ ǤͺȌ ʹͲ ȋͺǤͺȌ ͳͺ ȋ͹ǤʹȌ
    ‘™ ͳ ȋͲǤͻȌ ͵ ȋʹǤͶȌ ͺ ȋ͹ǤͳȌ Ͷ ȋ͵ǤʹȌ ͻ ȋ͵ǤͻȌ ͹ ȋʹǤͺȌ
    M Stage at Initial Diagnosis, n (%)
    Ͳ Ͷͳ ȋ͵ͷǤ͹Ȍ ͺʹ ȋ͸͸ǤͳȌ ͷͳ ȋͶͷǤͳȌ ͸͹ ȋͷ͵Ǥ͸Ȍ ͻʹ ȋͶͲǤͶȌ ͳͶͻ ȋͷͻǤͺȌ
    ͳ ʹ͹ ȋʹ͵ǤͷȌ ͳͷ ȋͳʹǤͳȌ ʹ͸ ȋʹ͵ǤͲȌ ʹ͹ ȋʹͳǤ͸Ȍ ͷ͵ ȋʹ͵ǤʹȌ Ͷʹ ȋͳ͸ǤͻȌ
    ‘™ ͸ ȋͷǤʹȌ ͹ ȋͷǤ͸Ȍ Ͷ ȋ͵ǤͷȌ Ͷ ȋ͵ǤʹȌ ͳͲ ȋͶǤͶȌ ͳͳ ȋͶǤͶȌ
    Stage at Baseline, n (%)
     ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ ͳ ȋͲǤͶȌ ͳ ȋͲǤͶȌ
     Ͳ ȋͲǤͲȌ ʹ ȋͳǤ͸Ȍ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ʹ ȋͲǤͺȌ
     Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ ͳ ȋͲǤͶȌ
     ͺ ȋ͹ǤͲȌ Ͷ ȋ͵ǤʹȌ ͹ ȋ͸ǤʹȌ ͳͳ ȋͺǤͺȌ ͳͷ ȋ͸Ǥ͸Ȍ ͳͷ ȋ͸ǤͲȌ
     ͳ ȋͲǤͻ  ʹ ȋͳǤ͸  ʹ ȋͳǤͺȌ ͳ ȋͲǤͺȌ ͵ ȋͳǤ͵Ȍ ͵ ȋͳǤʹȌ
     ͳ ȋͲǤͻ  ʹ ȋͳǤ͸Ȍ ͳ ȋͲǤͻȌ ʹ ȋͳǤ͸Ȍ ʹ ȋͲǤͻȌ Ͷ ȋͳǤ͸Ȍ
     Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ ͳ ȋͲǤͶȌ
    ‘™ ͻͳ ȋ͹ͻǤͳȌ ͳͲ͵ ȋͺ͵ǤͳȌ ͺͺ ȋ͹͹ǤͻȌ ͳͲ͵ ȋͺʹǤͶȌ ͳ͹ͻ ȋ͹ͺǤͷȌ ʹͲ͸ ȋͺʹǤ͹ 
    T Stage at Baseline, n (%)
    ͳ ʹ ȋͳǤ͹Ȍ ͸ ȋͶǤͺȌ ʹ ȋͳǤͺȌ ͵ ȋʹǤͶȌ Ͷ ȋͳǤͺȌ ͻ ȋ͵Ǥ͸Ȍ
    ʹ ͸ ȋͷǤʹȌ ͹ ȋͷǤ͸Ȍ ͺ ȋ͹ǤͳȌ ͹ ȋͷǤ͸Ȍ ͳͶ ȋ͸ǤͳȌ ͳͶ ȋͷǤ͸Ȍ
    ͵ ͵ ȋʹǤ͸Ȍ ͵ ȋʹǤͶȌ Ͳ ȋͲǤͲȌ Ͷ ȋ͵ǤʹȌ ͵ ȋͳǤ͵Ȍ ͹ ȋʹǤͺȌ
    Ͷ ͺ ȋ͹ǤͲȌ Ͷ ȋ͵ǤʹȌ Ͷ ȋ͵ǤͷȌ ͹ ȋͷǤ͸Ȍ ͳʹ ȋͷǤ͵Ȍ ͳͳ ȋͶǤͶȌ
    ‘™ ʹͶ ȋʹͲǤͻȌ ͵Ͳ ȋʹͶǤʹ  ʹͷ ȋʹʹǤͳ  ʹͻ ȋʹ͵Ǥʹ  Ͷͻ ȋʹͳǤͷ  ͷͻ ȋʹ͵Ǥ͹Ȍ
    N Stage at Baseline, n (%)
    Ͳ ͺ ȋ͹ǤͲȌ ͸ ȋͶǤͺȌ ͵ ȋʹǤ͹Ȍ ͻ ȋ͹ǤʹȌ ͳͳ ȋͶǤͺȌ ͳͷ ȋ͸ǤͲȌ
    ͳ Ͷ ȋ͵ǤͷȌ ͳͲ ȋͺǤͳȌ ͸ ȋͷǤ͵Ȍ ͹ ȋͷǤ͸Ȍ ͳͲ ȋͶǤͶȌ ͳ͹ ȋ͸ǤͺȌ
    ʹ Ͷ ȋ͵ǤͷȌ ͵ ȋʹǤͶȌ ͵ ȋʹǤ͹Ȍ Ͷ ȋ͵ǤʹȌ ͹ ȋ͵ǤͳȌ ͹ ȋʹǤͺȌ
    ͵ ͵ ȋʹǤ͸Ȍ ͵ ȋʹǤͶȌ ͳ ȋͲǤͻȌ Ͷ ȋ͵ǤʹȌ Ͷ ȋͳǤͺȌ ͹ ȋʹǤͺȌ
    ‘™ ʹͶ ȋʹͲǤͻȌ ʹͺ ȋʹʹǤ͸Ȍ ʹ͹ ȋʹ͵ǤͻȌ ʹ͹ ȋʹͳǤ͸Ȍ ͷͳ ȋʹʹǤͶȌ ͷͷ ȋʹʹǤͳȌ
    M Stage at Baseline, n (%)
    Ͳ ͵ ȋʹǤ͸Ȍ ͷ ȋͶǤͲȌ Ͳ ȋͲǤͲȌ ͸ ȋͶǤͺȌ ͵ ȋͳǤ͵Ȍ ͳͳ ȋͶǤͶȌ
    ͳ ʹ͹ ȋʹ͵ǤͷȌ ͵͵ ȋʹ͸Ǥ͸Ȍ ʹͷ ȋʹʹǤͳȌ ͵͹ ȋʹͻǤ͸Ȍ ͷʹ ȋʹʹǤͺȌ ͹Ͳ ȋʹͺǤͳȌ
    ‘™ ͳ͵ ȋͳͳǤ͵Ȍ ͳ͵ ȋͳͲǤͷȌ ͳͶ ȋͳʹǤͶȌ ͳͲ ȋͺǤͲȌ ʹ͹ ȋͳͳǤͺȌ ʹ͵ ȋͻǤʹȌ
    Sites of Disease, n (%)
    ”‡ƒ•– ʹͶ ȋʹͲǤͻȌ ͳͷ ȋͳʹǤͳ  ʹͳ ȋͳͺǤ͸  ʹͺ ȋʹʹǤͶ  Ͷͷ ȋͳͻǤ͹  Ͷ͵ ȋͳ͹Ǥ͵Ȍ
    ‘‡ ͳͲͳ ȋͺ͹Ǥͺ  ͻͳ ȋ͹͵ǤͶ  ͻ͵ ȋͺʹǤ͵  ͻͳ ȋ͹ʹǤͺ  ͳͻͶ ȋͺͷǤͳȌ ͳͺʹ ȋ͹͵ǤͳȌ
    ‘‡‘Ž› ͳͶ ȋͳʹǤʹ  ʹͶ ȋͳͻǤͶ  ͳͶ ȋͳʹǤͶ  ͳͷ ȋͳʹǤͲ  ʹͺ ȋͳʹǤ͵  ͵ͻ ȋͳͷǤ͹ 
    ›’Š‘†‡• ͵Ͷ ȋʹͻǤ͸Ȍ ͵Ͷ ȋʹ͹ǤͶ  ʹ͹ ȋʹ͵Ǥͻ  Ͷͳ ȋ͵ʹǤͺ  ͸ͳ ȋʹ͸Ǥͺ  ͹ͷ ȋ͵ͲǤͳ 
    ‹• ‡”ƒŽȏͳȐ ͺͳ ȋ͹ͲǤͶ  ͺʹ ȋ͸͸Ǥͳ  ͺ͵ ȋ͹͵Ǥͷ  ͺͷ ȋ͸ͺǤͲ  ͳ͸Ͷ ȋ͹ͳǤͻ  ͳ͸͹ ȋ͸͹ǤͳȌ
    ”ƒ‹ ͵ ȋʹǤ͸Ȍ ͳ ȋͲǤͺȌ ʹ ȋͳǤͺȌ ͳ ȋͲǤͺȌ ͷ ȋʹǤʹȌ ʹ ȋͲǤͺȌ
    ‹˜‡” ͸Ͳ ȋͷʹǤʹȌ ͸ʹ ȋͷͲǤͲ  ͸Ͷ ȋͷ͸Ǥ͸  Ͷͻ ȋ͵ͻǤʹȌ ͳʹͶ ȋͷͶǤͶȌ ͳͳͳ ȋͶͶǤ͸Ȍ
    —‰ ʹ͹ ȋʹ͵ǤͷȌ ʹͻ ȋʹ͵ǤͶȌ ͵ͳ ȋʹ͹ǤͶȌ ͵͹ ȋʹͻǤ͸Ȍ ͷͺ ȋʹͷǤͶ  ͸͸ ȋʹ͸Ǥͷ 
    –Š‡”‹–‡• ʹ͸ ȋʹʹǤ͸Ȍ ʹͳ ȋͳ͸Ǥͻ  ͳͺ ȋͳͷǤͻ  ͵Ͳ ȋʹͶǤͲ  ͶͶ ȋͳͻǤ͵  ͷͳ ȋʹͲǤͷȌ
    „†‘‹ƒŽ ʹ ȋͳǤ͹  ͵ ȋʹǤͶȌ ͳ ȋͲǤͻȌ Ͷ ȋ͵ǤʹȌ ͵ ȋͳǤ͵Ȍ ͹ ȋʹǤͺȌ
    ƒ˜‹–›
    †”‡ƒŽ Žƒ† ͷ ȋͶǤ͵  ͵ ȋʹǤͶȌ ͷ ȋͶǤͶȌ Ͷ ȋ͵ǤʹȌ ͳͲ ȋͶǤͶȌ ͹ ȋʹǤͺȌ
    ‡”˜‹š–‡”‹ Ͳ ȋͲǤͲ  Ͳ ȋͲǤͲȌ ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ Ͳ ȋͲǤͲȌ
    Š‡•–ƒŽŽ Ͳ ȋͲǤͲȌ ͵ ȋʹǤͶȌ ͵ ȋʹǤ͹Ȍ ͺ ȋ͸ǤͶȌ ͵ ȋͳǤ͵Ȍ ͳͳ ȋͶǤͶȌ
    •‘’Šƒ‰—• Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ Ͳ ȋͲǤͲȌ ʹ ȋͲǤͺȌ
    ‡ƒ†† ͳ ȋͲǤͻ  ͳ ȋͲǤͺȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ ͳ ȋͲǤͶȌ
    ‡ 
    –‡•–‹‡ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ
    ‹†‡› ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ʹ ȋͳǤ͸Ȍ ͳ ȋͲǤͶȌ ʹ ȋͲǤͺȌ

    ͺͻ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Elacestrant SOC Total
    ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd ESR1-mut ESR1-mut-nd
    ‡†‹ƒ•–‹— ͸ ȋͷǤʹ  ͵ ȋʹǤͶ  ͳ ȋͲǤͻȌ ʹ ȋͳǤ͸Ȍ ͹ ȋ͵ǤͳȌ ͷ ȋʹǤͲȌ
    –Š‡” ͳ ȋͲǤͻ  Ͷ ȋ͵Ǥʹ  ͳ ȋͲǤͻȌ Ͷ ȋ͵ǤʹȌ ʹ ȋͲǤͻȌ ͺ ȋ͵ǤʹȌ
    ƒ ”‡ƒ• ͳ ȋͲǤͻȌ ʹ ȋͳǤ͸Ȍ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ ͳ ȋͲǤͶȌ ͵ ȋͳǤʹȌ
    ‡”‹ ƒ”†‹— ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ ͳ ȋͲǤͶȌ ͳ ȋͲǤͶȌ
    ‹ ͸ ȋͷǤʹȌ ͵ ȋʹǤͶȌ ͷ ȋͶǤͶȌ Ͷ ȋ͵ǤʹȌ ͳͳ ȋͶǤͺȌ ͹ ȋʹǤͺȌ
    ‘ˆ–‹••—‡ ͷ ȋͶǤ͵  ͳ ȋͲǤͺȌ ͵ ȋʹǤ͹Ȍ ʹ ȋͳǤ͸Ȍ ͺ ȋ͵ǤͷȌ ͵ ȋͳǤʹȌ
    ’Ž‡‡ ͳ ȋͲǤͻ  ͳ ȋͲǤͺȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ ͳ ȋͲǤͶȌ
    –‘ƒ Š ͳ ȋͲǤͻȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ Ͳ ȋͲǤͲȌ
    Š›”‘‹† Žƒ† Ͳ ȋͲǤͲ  Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͺȌ Ͳ ȋͲǤͲȌ ͳ ȋͲǤͶȌ
    Number of Metastatic Sites, n (%)
    Ͳ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ Ͳ ȋͲǤͲȌ
    ͳ ͳ͸ ȋͳ͵ǤͻȌ ͵ͷ ȋʹͺǤʹȌ ͳͻ ȋͳ͸ǤͺȌ ʹ͹ ȋʹͳǤ͸Ȍ ͵ͷ ȋͳͷǤͶȌ ͸ʹ ȋʹͶǤͻȌ
    ʹ Ͷ͵ ȋ͵͹ǤͶȌ ͵ͳ ȋʹͷǤͲȌ ͵Ͷ ȋ͵ͲǤͳȌ ͵ͺ ȋ͵ͲǤͶȌ ͹͹ ȋ͵͵ǤͺȌ ͸ͻ ȋʹ͹Ǥ͹Ȍ
    εα͵ ͶͶ ȋ͵ͺǤ͵Ȍ ͵Ͷ ȋʹ͹ǤͶȌ Ͷͳ ȋ͵͸Ǥ͵Ȍ Ͷͳ ȋ͵ʹǤͺȌ ͺͷ ȋ͵͹Ǥ͵Ȍ ͹ͷ ȋ͵ͲǤͳȌ
    ȏͳȐ  Ž—†‡•Ž—‰ǡŽ‹˜‡”ǡ„”ƒ‹ǡ’Ž‡—”ƒŽǡƒ†’‡”‹–‘‡ƒŽ‹˜‘Ž˜‡‡–

    ƒˆ‡–›ƒ†ˆˆ‡ –‹˜‡‡••‡•—Ž–•ˆ‘”–Š‡ —ƒ”†ƒ–͵͸ͲšŽ‹‹ ƒŽ”‹†‰‹‰–—†›ˆ‘”ESR —–ƒ–‹‘•


    g. Safety Results
    ƒ–ƒ”‡‰ƒ”†‹‰–Š‡•ƒˆ‡–›‘ˆ̻ȋ‡Žƒ ‡•–”ƒ–Ȍ–Š‡”ƒ’›ƒ”‡’”‡•‡–‡†‹–Š‡†”—‰ƒ’’”‘˜ƒŽǤ
    ‡ˆ‡”–‘–Š‡̻ȋ‡Žƒ ‡•–”ƒ–ȌŽƒ„‡Žˆ‘”‘”‡‹ˆ‘”ƒ–‹‘Ǥ‘ƒ†˜‡”•‡‡˜‡–•™‡”‡”‡’‘”–‡†‹
    –Š‡ ‘†— –‘ˆ–Š‡†‹ƒ‰‘•–‹ •–—†‹‡•—•‡†–‘•—’’‘”––Š‹•Ǥ
    h. Effectiveness Results
    ‹‹‹Ǥ  ‹ƒ–‹‡–•‘•‹–‹˜‡„› —ƒ”†ƒ–͵͸Ͳšˆ‘”ESR1‹••‡•‡—–ƒ–‹‘•
    Š‡  ‘„•‡”˜‡†‹–Š‡ESR1Ǧ—–’‘’—Žƒ–‹‘–”‡ƒ–‡†™‹–Š̻ȋ‡Žƒ ‡•–”ƒ–Ȍ˜•Ǥ
    ™ƒ•ͲǤͷͶ͸ǡͻͷΨ ͲǤ͵ͺ͹ȂͲǤ͹͸ͺǡ’αͲǤͲͲͲͷȋFigure 12Ȍǡ™Š‹ Š‡––Š‡†‹ƒ‰‘•–‹ •–—†›
    ƒ ‡’–ƒ ‡ ”‹–‡”‹‘Ǥ‹‹Žƒ””‡•—Ž–•™‡”‡•‡‡‹–Š‡•‡•‹–‹˜‹–›ƒƒŽ›•‹•—•‹‰ƒ—•–”ƒ–‹ˆ‹‡†‘š
    ”‘’‘”–‹‘ƒŽ ƒœƒ”†‘†‡Ž™‹–Šƒ‘„•‡”˜‡† ‘ˆͲǤͷ͵ͳͻͷΨ ͲǤ͵͹ͺǦͲǤ͹Ͷʹǡ’αͲǤͲͲͲʹǤ
    ‡‘•–”ƒ–‹‘‘ˆ Ž‹‹ ƒŽ‡ˆˆ‹ ƒ ›‹–Š‡ͳǦ—–’‘’—Žƒ–‹‘‹•ˆ—”–Š‡”•—’’‘”–‡†„› Ž‡ƒ”
    •‡’ƒ”ƒ–‹‘‘ˆ–Š‡–”‡ƒ–‡–ƒ”•‹–Š‡ƒ’ŽƒǦ‡‹‡”’Ž‘–‘ˆ Ǥ

    ͻͲ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    
    Figure 12. Progression-Free Survival for Elacestrant versus SOC in ESR1-mut Subjects
    Š‡‡†‹ƒ ‹–Š‡ESR1Ǧ—–’‘’—Žƒ–‹‘–”‡ƒ–‡†™‹–Š̻ȋ‡Žƒ ‡•–”ƒ–Ȍ™ƒ•͵Ǥ͹ͺ
    ‘–Š•ȋͻͷΨ ʹǤͳ͹Ȃ͹Ǥʹ͸Ȍ˜•ǤͳǤͺ͹‘–Š•ȋͻͷΨ ͳǤͺ͹ȂʹǤͳͶȌǤŠ‡ ”ƒ–‡ƒ–͵ǡ͸ǡͳʹ
    ƒ†ͳͺ‘–Š•ƒŽ•‘†‡‘•–”ƒ–‡†’”‘Ž‘‰‡†•—”˜‹˜ƒŽ‘ˆESR1Ǧ—–•—„Œ‡ –•–”‡ƒ–‡†™‹–Š
    ̻ȋ‡Žƒ ‡•–”ƒ–Ȍ˜•ǤȋTable 65 Ǥ

    Table 65. Efficacy Results for EMERALD (Patients with ESR1 Missense Mutations)
    SOC (Fulvestrant or
    ORSERDU an Aromatase Inhibitor)
    (N = 115) (N=113)
    Progression-free Survival (PFS)a
    —„‡”‘ˆ ˜‡–•ǡȋΨȌ ͸ʹȋͷ͵ǤͻȌ ͹ͺȋ͸ͻǤͲȌ
    ‡†‹ƒ ‘–Š•„ȋͻͷΨ Ȍ ͵Ǥ͹ͺȋʹǤͳ͹ǡ͹Ǥʹ͸Ȍ ͳǤͺ͹ȋͳǤͺ͹ǡʹǤͳͶȌ
    ƒœƒ”†”ƒ–‹‘ ȋͻͷΨ Ȍ ͲǤͷͷȋͲǤ͵ͻǡͲǤ͹͹Ȍ
    ’Ǧ˜ƒŽ—‡†ȋ•–”ƒ–‹ˆ‹‡†Ž‘‰Ǧ”ƒȌ ͲǤͲͲͲͷ
    Overall Survival (OS)
    —„‡”‘ˆ˜‡–•ǡȋΨȌ ͸ͳȋͷ͵Ȍ ͸Ͳȋͷ͵Ȍ
    ƒœƒ”†”ƒ–‹‘ ȋͻͷΨ Ȍ ͲǤͻͲȋͲǤ͸͵ǡͳǤ͵ͲȌ
    ’Ǧ˜ƒŽ—‡†ȋ•–”ƒ–‹ˆ‹‡†Ž‘‰Ǧ”ƒȌ ‡
    ƒ ”‡•—Ž–•„ƒ•‡†‘„Ž‹†‡†‹ƒ‰‹‰”‡˜‹‡™ ‘‹––‡‡
    „ƒ’ŽƒǦ‡‹‡”‡•–‹ƒ–‡ǢͻͷΨ „ƒ•‡†‘–Š‡”‘‘‡›‡”Ǧ”‘™Ž‡›‡–Š‘†—•‹‰ƒŽ‹‡ƒ”–”ƒ•ˆ‘”ƒ–‹‘
    ‘š’”‘’‘”–‹‘ƒŽŠƒœƒ”†•‘†‡Ž•–”ƒ–‹ˆ‹‡†„›’”‹‘”–”‡ƒ–‡–™‹–Šˆ—Ž˜‡•–”ƒ–ȋ›‡•˜•‘Ȍƒ†˜‹• ‡”ƒŽ‡–ƒ•–ƒ•‹•ȋ›‡•˜•
    ‘Ȍ
    †–”ƒ–‹ˆ‹‡†Ž‘‰Ǧ”ƒ–‡•––™‘Ǧ•‹†‡†’Ǧ˜ƒŽ—‡
    ‡Ȃ‘–•–ƒ–‹•–‹ ƒŽŽ›•‹‰‹ˆ‹ ƒ–

    ‹ƒ‰‘•–‹ –—†›‘ Ž—•‹‘•


    Š‡†‹ƒ‰‘•–‹ •–—†›‡––Š‡’”‡•’‡ ‹ˆ‹‡†ƒ ‡’–ƒ ‡ ”‹–‡”‹‘ƒ••‘ ‹ƒ–‡†™‹–Š‹–•’”‹ƒ”›‘„Œ‡ –‹˜‡Ǥ
    ”—‰‡ˆˆ‹ ƒ ›™ƒ•‡•–ƒ„Ž‹•Š‡†„›†‡‘•–”ƒ–‹‰–Šƒ––Š‡  ȋͲǤͷͷǡͻͷΨ ͲǤ͵ͻȂͲǤ͹͹Ȍ™ƒ•
    •–ƒ–‹•–‹ ƒŽŽ›•‹‰‹ˆ‹ ƒ–ƒ–’αͲǤͲͲͲͷˆ‘”•—„Œ‡ –•ˆ”‘–Š‡ͳͻͲͳǦ͵Ͳͺ Ž‹‹ ƒŽ•–—†›’‘•‹–‹˜‡ˆ‘”
    ESR1‹••‡•‡—–ƒ–‹‘•„› —ƒ”†ƒ–͵͸ͲšȋESR1Ǧ—–Ȍ–”‡ƒ–‡†™‹–Š‡Žƒ ‡•–”ƒ–”‡Žƒ–‹˜‡–‘Ǥ

    ͻͳ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Š—•ǡ‡Žƒ ‡•–”ƒ–†‡‘•–”ƒ–‡† Ž‹‹ ƒŽŽ›‡ƒ‹‰ˆ—Ž‡ˆˆ‹ ƒ ›‹–Š‡ —ƒ”†ƒ–͵͸ͲšǦ’‘•‹–‹˜‡
    ‹–‡†‡†—•‡’‘’—Žƒ–‹‘ǤŠ‹••—’’‘”–•–Š‡ Ž‹‹ ƒŽ˜ƒŽ‹†‹–›‘ˆ —ƒ”†ƒ–͵͸Ͳš–‘ƒ‹†‹–Š‡•‡Ž‡ –‹‘
    ‘ˆ„”‡ƒ•– ƒ ‡”•—„Œ‡ –•™‹–ŠESR1—–ƒ–‹‘•†‡–‡ –‡†‹’Žƒ•ƒˆ‘”–”‡ƒ–‡–™‹–Š‡Žƒ ‡•–”ƒ–Ǥ

    8. Additional Guardant360 CDx Variant Details


    Table 66. Guardant360 CDx Reportable Alterations Based on cDNA and Amino Acid Changes
    Gene (Transcript ID) Reportable cDNA and Amino Acid Changes
    AKT1ȋ̴ͲͲͳͲͳͶͶ͵ʹȌ ͳ͹ǡ͸ͻ̴͹͹†—’
    ALKȋ̴ͲͲͶ͵ͲͶȌ ͳͳʹ͵ǢͳͳͷͳǢͳͳͷʹǢͳͳͷʹǢͳͳͷʹǢͳͳͷ͸Ǣͳͳͷ͸Ǣͳͳͷ͸Ǣ ͳͳ͹ͳǢ ͳͳ͹ͳǢ
    ͳͳ͹ͳǢ ͳͳ͹ͶǢ ͳͳ͹ͶǢ ͳͳ͹ͶǢ ͳͳ͹Ͷ Ǣ ͳͳ͹ͶǢ ͳͳ͹ͷǢ ͳͳ͹ͷǢͳͳͺͲǢͳͳͻ͸Ǣ
    ͳͳͻ͸Ǣͳͳͻͺ Ǣ ͳʹͲʹǢ ͳʹͲʹ†‡ŽǢͳʹͲ͵ǢͳʹͲ͸ǢͳʹͲ͸ ǢͳʹͲ͸ǢͳʹͳͲǢ
    ͳʹʹͷǢͳʹͶʹǢ ͳʹͶͷǢ ͳʹ͸ͻǢͳʹ͹ͷǢͶ͵Ǣͷͷ͹
    APCȋ̴ͲͲͳͳʹ͹ͷͳͳȌ Ǥͳ͵ͳʹΪͳ εǢ Ǥͳ͵ͳʹΪͳ εǢ ǤͳͶͲͻǦͳ εǢ ǤͳͷͶͺΪͳ εǢ Ǥͳ͹ͶͶǦͳ εǢ Ǥͷ͵ʹǦͳ εǢ
    Ǥ͹͵ͲǦͳ εǢ Ǥͺ͵ͶΪͳ εǢ Ǥͺ͵ͶΪʹεǢ Ǥͺ͵ͷǦͳ ε
    ͳͲͲͲȗǢͳͲʹ͸ǢͳͲ͵ͲȗǢͳͲ͵ͳȗǢͳͲͶͷȗǢͳͲͶͻȗǢ ͳͲͷͷˆ•ǢͳͲ͸ͳȗǢͳͲ͸ʹˆ•Ǣ
    ͳͲ͸͸ˆ•ǢͳͲ͸ͺȗǢͳͲͺͲȗǢͳͳͲͶȗǢͳͳͳͳȗǢͳͳͳͶȗǢ ͳͳʹͲǢͳͳʹ͵ȗǢͳͳͶʹˆ•ǢͳͳͶͻȗǢ
    ͳͳͷ͸ȗǢͳͳͷ͸ˆ•Ǣͳͳ͸ͷȗǢͳͳ͸ͺȗǢͳͳ͹ͷȗǢͳͳͺʹȗǢͳͳͺ͵ȗǢͳͳͻʹȗǢͳͳͻ͸ȗǢͳʹͲͶȗǢ
    ͳʹͲͻȗǢͳʹͳ͵ˆ•ǢͳʹͶͶȗǢͳʹ͸Ͳˆ•ǢͳʹͺͳȗǢͳʹͺʹȗǢͳʹͺ͸ȗǢ ͳʹͺ͹ˆ•ǢͳʹͺͺȗǢ ͳʹͺͺȗǢ
    ͳʹͺͺˆ•ǢͳʹͻͳȗǢͳʹͻͶȗǢͳʹͻͶˆ•ǢͳʹͻͷȗǢͳʹͻͷˆ•Ǣͳʹͻ͸ˆ•Ǣͳʹͻͺˆ•Ǣͳ͵Ͳͳˆ•Ǣ
    ͳ͵Ͳʹˆ•Ǣͳ͵Ͳ͵ȗǢ ͳ͵ͲͶˆ•Ǣͳ͵Ͳ͸ȗǢͳ͵Ͳ͸ˆ•Ǣ ͳ͵Ͳ͹ˆ•Ǣͳ͵ͲͻȗǢͳ͵Ͳͻˆ•Ǣͳ͵ͳͲȗǢ
    ͳ͵ͳͲˆ•Ǣ ͳ͵ͳͳˆ•Ǣ ͳ͵ͳʹȗǢ ͳ͵ͳʹˆ•Ǣͳ͵ͳͶˆ•Ǣͳ͵ͳͷȗǢͳ͵ͳ͹ȗǢͳ͵ͳͻˆ•Ǣͳ͵ʹʹȗǢ
    ͳ͵ʹʹˆ•Ǣͳ͵ʹ͹ȗǢͳ͵ʹͺȗǢͳ͵͵ͳȗǢͳ͵͵ͳˆ•Ǣͳ͵͵ͺȗǢͳ͵͵ͺˆ•Ǣͳ͵Ͷʹˆ•Ǣͳ͵ͶͷȗǢͳ͵Ͷ͸ȗǢ
    ͳ͵Ͷ͸ˆ•Ǣͳ͵ͶͻȗǢͳ͵ͷʹˆ•Ǣͳ͵ͷ͵ȗǢͳ͵ͷ͵ˆ•Ǣͳ͵ͷͷˆ•Ǣͳ͵ͷ͸ȗǢ ͳ͵ͷ͹ȗǢͳ͵͸ͲȗǢ
    ͳ͵͸Ͷˆ•Ǣ ͳ͵͸ͷˆ•Ǣͳ͵͸͹ȗǢͳ͵͹ͲȗǢͳ͵͹Ͳˆ•Ǣͳ͵͹ͶȗǢͳ͵͹͸ȗǢͳ͵͹͸ˆ•Ǣͳ͵͹ͺȗǢ
    ͳ͵͹ͻȗǢͳ͵ͺ͵ˆ•Ǣͳ͵ͺ͸ȗǢͳ͵ͺ͹ȗǢͳ͵ͻʹȗǢͳ͵ͻͶˆ•Ǣͳ͵ͻͷǢ ͳ͵ͻ͸ˆ•Ǣͳ͵ͻ͹ȗǢ
    ͳ͵ͻͻˆ•ǢͳͶͲͲǢͳͶͲͲˆ•ǢͳͶͲʹǢͳͶͲ͸ȗǢͳͶͲ͹ˆ•ǢͳͶͲͺȗǢͳͶͳͳȗǢͳͶͳͳˆ•Ǣ
    ͳͶͳͶȗǢͳͶͳͶˆ•ǢͳͶͳͷˆ•Ǣ ͳͶͳ͹ˆ•Ǣ ͳͶͳͺˆ•ǢͳͶʹͳˆ•ǢͳͶʹʹˆ•ǢͳͶʹ͵ˆ•ǢͳͶʹͶˆ•Ǣ
    ͳͶʹ͹ˆ•ǢͳͶʹͻȗǢͳͶ͵Ͳˆ•ǢͳͶ͵ͳˆ•ǢͳͶ͵Ͷˆ•ǢͳͶ͵ͷˆ•ǢͳͶ͵ͺˆ•ǢͳͶ͵ͻˆ•ǢͳͶͶͲˆ•Ǣ
    ͳͶͶͳˆ•ǢͳͶͶʹˆ•ǢͳͶͶ͵ˆ•ǢͳͶͶͶȗǢͳͶͶͷˆ•ǢͳͶͶ͹ȗǢͳͶͶͻȗǢͳͶͶͻˆ•ǢͳͶͷͲȗǢ
    ͳͶͷͲˆ•ǢͳͶͷͳȗǢͳͶͷʹˆ•ǢͳͶͷͷˆ•ǢͳͶͷ͹ˆ•ǢͳͶ͸ͳȗǢͳͶ͸Ͷˆ•ǢͳͶ͸ͷˆ•Ǣ ͳͶ͸͸Ǣ
    ͳͶ͸ͻˆ•ǢͳͶ͹ʹˆ•ǢͳͶ͹͹ȗǢͳͶ͹ͻˆ•ǢͳͶͺͲȗǢͳͶͺͷˆ•ǢͳͶͺ͸ˆ•ǢͳͶͺ͹ˆ•ǢͳͶͺͺˆ•Ǣ
    ͳͶͺͻˆ•Ǣ ͳͶͻͲˆ•Ǣ ͳͶͻͳˆ•ǢͳͶͻʹˆ•ǢͳͶͻ͵ˆ•ǢͳͶͻͶˆ•ǢͳͶͻͷˆ•ǢͳͶͻ͸ˆ•ǢͳͶͻͺˆ•Ǣ
    ͳͷͲͳˆ•Ǣͳͷͳ͵ȗǢ ͳͷͳͷˆ•Ǣͳͷͳͻˆ•ǢͳͷʹͳȗǢͳͷʹͻȗǢͳͷ͵ͲȗǢͳͷ͵ͳˆ•Ǣͳͷ͵͸ȗǢͳͷ͵ͺȗǢ
    ͳͷ͵ͺˆ•Ǣͳͷ͵ͻȗǢͳͷͶͶȗǢͳͷͶͷȗǢͳͷͶ͸ˆ•ǢͳͷͶ͹ȗǢͳͷͶͺˆ•ǢͳͷͶͻȗǢͳͷͷͲȗǢͳͷͷʹȗǢ
    ͳͷͷʹˆ•Ǣͳͷͷ͵ˆ•ǢͳͷͷͶȗǢͳͷͷ͸ˆ•Ǣͳͷ͸ͳˆ•Ǣͳͷ͸ͶȗǢͳͷ͸͹ȗǢͳͷ͹͵ȗǢͳͷ͹͸ȗǢ
    ͳͷ͹͸ˆ•Ǣͳͷ͹ͺˆ•Ǣ ͳͷ͹ͻˆ•Ǣͳͷͻ͵ˆ•ǢͳͷͻͶˆ•Ǣͳ͸ʹͳȗǢͳ͸͵͸ˆ•Ǣͳ͸ͺ͹ȗǢͳ͹Ͳˆ•Ǣ
    ͳ͹ͳ͵ˆ•Ǣͳ͹͵ˆ•Ǣͳ͹ͻʹˆ•ǢͳͺͷͺȗǢͳͺ͹ͻˆ•ǢͳͻʹͲȗǢͳͻͻǢ ʹͲ͸͵ˆ•ǢʹͳȗǢʹͳͳȗǢ
    ʹͳ͵ȗǢʹͳͶͲȗǢʹͳ͸ȗǢʹͳ͸͸ǢʹͳͻͶˆ•ǢʹʹͲͶȗǢʹʹʹȗǢʹʹ͵͹ȗǢʹʹͷȗǢʹ͵ͲǢ
    ʹ͵Ͳ͹Ǣʹ͵ͳͲȗǢʹ͵ʹȗǢ ʹ͵͵ʹˆ•Ǣʹ͵͸ȗǢʹ͵ͺʹˆ•ǢʹͶͶͳȗǢʹͶ͹ȗǢʹͷͲͶȗǢʹͷͷͷȗǢ
    ʹͷ͸ͶȗǢʹͷͻǢ ʹ͸ͳͷˆ•Ǣʹ͸ͳͻȗǢʹ͹ͳͶǢ ʹ͹͹ͲǢʹͺͲȗǢʹͺ͵ȗǢʹͻͲǢ ʹͻͺˆ•Ǣ
    ͵Ͳˆ•Ǣ͵ͲʹȗǢ͵͵ʹȗǢ͵ͶͺȗǢ͵ͷʹȗǢͶͲͷȗǢͶͳʹȗǢͶʹͳȗǢͶʹͶȗǢͶ͵͸ˆ•ǢͶͷʹˆ•Ǣ
    Ͷͷ͹ˆ•ǢͶ͹͵ȗǢͶͺͲȗǢͶͻͻȗǢͷ͵ʹȗǢͷ͵ͶȗǢͷͶͲȗǢͷͶͺȗǢͷͶͺˆ•Ǣͷͷ͵ȗǢͷͷͶȗǢ
    ͷ͸ͶȗǢͷ͹ͶȗǢͷͺͳˆ•ǢͷͺʹȗǢͷͺʹˆ•Ǣͷͺ͵ȗǢͷͺͷˆ•Ǣͷͺ͹ˆ•Ǣͷͻ͵ȗǢͷͻ͸ȗǢ͸ͳ͸ˆ•Ǣ
    ͸ͳͺˆ•Ǣ͸ʹʹȗǢ͸ʹʹˆ•Ǣ͸ʹ͹ˆ•Ǣ͸͵Ͷˆ•Ǣ͸ͶͲ Ǣ͸ͷͺȗǢ͸͸ͷˆ•Ǣ͸͹ͲȗǢ͸ͺͷȗǢ͹Ͳ͵ˆ•Ǣ
    ͹ʹͳȗǢ͹Ͷ͹ȗǢ͹ͷ͹ȗǢ͹͸͹ȗǢ͹͹ͲȗǢ͹͹ͳȗǢ ͹͹͵ˆ•Ǣ͹͹ͻȗǢ͹ͺˆ•Ǣ͹ͺʹȗǢ͹ͺ͸Ǣ͹ͺͻȗǢ
    ͹ͻ͸ȗǢ͹ͻͻˆ•ǢͺͲͷȗǢ ͺͳͶˆ•Ǣͺʹʹˆ•Ǣͺʹͷˆ•Ǣͺʹ͸ˆ•Ǣͺ͵ʹˆ•Ǣͺ͵͹ȗǢͺͶ͵ˆ•ǢͺͶͻˆ•Ǣ
    ͺͷͶˆ•ǢͺͷͷȗǢͺͷͷˆ•Ǣͺ͸ͻˆ•Ǣͺ͹͸ȗǢͻͳͷˆ•ǢͻͳͺȗǢͻ͵ͷȗǢͻ͵ͷˆ•Ǣͻ͵͸ˆ•ǢͻͶͲȗǢ
    ͻͶͳȗǢͻͶʹˆ•ǢͻͶ͵ȗǢͻͶ͹ˆ•Ǣͻͷ͵ȗǢͻ͹͸ˆ•Ǣ ͻ͹͹ˆ•Ǣͻ͹ͺȗǢͻͺͶȗǢͻͻͳȗǢͻͻ͵ȗǢ
    ͻͻ͹ˆ•Ǣͻͻͻȗ
    ARȋ̴ͲͲͲͲͶͶȌ ʹ͹ͲǢ͸͵ͲǢ͸ͶͳȗǢ͹Ͳʹ Ǣ͹ͳ͸Ǣ͹ͶʹǢ͹ͷͲǢ ͹ͻ͸Ǣ ͺͳͶǢͺ͹͵Ǣ ͺ͹ͷǢ
    ͺ͹ͷǢͺ͹ͺǢͺ͹ͺǢͺͺ͹ Ǣͺͺͻ Ǣͺͻͳ Ǣͺͻ͸
    ARAFȋ̴ͲͲͳ͸ͷͶȌ ʹͳͶǢʹͳͶǢʹͳͶ ǢʹͳͶǢʹͳͶ

    ͻʹ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Gene (Transcript ID) Reportable cDNA and Amino Acid Changes
    BRAFȋ̴ͲͲͶ͵͵͵Ȍ ͵͸ͷǢͶͶͶǢͶ͸ʹǢͶ͸ʹ Ǣ Ͷ͸͵Ǣ Ͷ͸ͶǢ Ͷ͸͸Ǣ Ͷ͸͸Ǣ Ͷ͸͸Ǣ Ͷ͸͸ǢͶ͸͹Ǣ
    Ͷ͸ͺǢ Ͷ͸ͻǢ Ͷ͸ͻǢ Ͷ͸ͻǢ Ͷ͸ͻǢ Ͷ͸ͻǢ Ͷ͸ͻǢͶ͹ͳ ǢͶͺͷ ǢͶͻͻǢͷͲͳǢ
    ͷͲͷ ǢͷʹͷǢͷͺͳ ǢͷͺͳǢͷͺͳǢͷͺͳǢͷͺͳǢͷͺ͹Ǣͷͺ͹Ǣ ͷͻʹǢ ͷͻʹǢ
    ͷͻͶǢͷͻͶǢͷͻͶǢͷͻͶ ǢͷͻͶ ǢͷͻͶǢͷͻͶǢ ͷͻͷǢ ͷͻ͸Ǣ ͷͻ͸Ǣ ͷͻ͸Ǣ
    ͷͻ͸Ǣ ͷͻ͸Ǣͷͻ͹Ǣͷͻ͹Ǣͷͻ͹Ǣͷͻ͹ǢͷͻͻǢ͸ͲͲǢ͸ͲͲǢ͸ͲͲ Ǣ͸ͲͲǢ
    ͸ͲͲǢ͸ͲͲǢ͸ͲͲǢ͸ͲͲǢ͸ͲͳǢ͸ͲͳǢ͸ͲͳǢ͸ͲͳǢ͸Ͳͷ
    BRCA1ȋ̴ͲͲ͹ʹͻͶȌ ǫǢͳǢͳͳ͸Ͷ Ǣͳ͵ͻͷǢͳͶͲ͹ǢͳͶͺ͹ǢͳͶͻͷǢͳͶͻͷǢͳͶͻͷǢͳͷͷͻǢ
    ͳͷͷͻǢͳ͸ͷʹǢͳ͸ͷ͵Ǣͳ͸ͷͷ Ǣ ͳ͸ͷ͸Ǣͳ͸ͷ͹Ǣͳ͸͸Ͳ Ǣͳ͸ͺͷǢͳ͸ͺͷ Ǣ
    ͳ͸ͺ͸Ǣ ͳ͸ͺ͸Ǣͳ͸ͺͻǢͳ͸ͺͻǢͳ͸ͻͳ Ǣͳ͸ͻͳǢͳ͸ͻʹ Ǣͳ͸ͻʹǢͳ͸ͻʹǢ
    ͳ͸ͻ͸Ǣͳ͸ͻ͹Ǣͳ͸ͻͻǢͳ͸ͻͻǢͳ͸ͻͻǢͳ͹ͲͲǢͳ͹ͲʹǢͳ͹Ͳ͵ Ǣͳ͹Ͳ͵Ǣ
    ͳ͹ͲͶǢͳ͹ͲͷǢ ͳ͹Ͳ͸Ǣ ͳ͹Ͳ͸Ǣͳ͹ͲͺǢͳ͹ͲͺǢͳ͹ͳ͵Ǣͳ͹ͳͶ Ǣͳ͹ͳͷǢ
    ͳ͹ͳͷǢͳ͹ͳͷǢͳ͹ͳͺǢͳ͹ͳͺǢͳ͹ͳͺǢͳ͹ʹʹ Ǣ ͳ͹͵ͶǢ ͳ͹͵ͶǢͳ͹͵͸Ǣ
    ͳ͹͵͸Ǣͳ͹͵͸ Ǣ ͳ͹͵ͺǢ ͳ͹͵ͺǢͳ͹͵ͻǢͳ͹͵ͻ Ǣͳ͹͵ͻǢͳ͹͵ͻǢͳ͹Ͷͳ Ǣ
    ͳ͹Ͷ͵Ǣ ͳ͹Ͷ͸Ǣͳ͹ͶͻǢͳ͹ͷͳǢͳ͹ͷʹǢͳ͹ͷʹǢͳ͹ͷ͵Ǣͳ͹ͷ͸Ǣ ͳ͹͸ͳ Ǣ
    ͳ͹͸ͳǢ ͳ͹͸͵Ǣͳ͹͸ͶǢ ͳ͹͸͸Ǣ ͳ͹͹ͲǢͳ͹͹͵ Ǣͳ͹͹ͷǢͳ͹͹ͷǢͳ͹͹ͷǢ
    ͳ͹ͺͲǢͳ͹ͺ͹Ǣ ͳ͹ͺͺǢ ͳ͹ͺͺǢͳ͹ͺͻǢͳͺǢ ͳͺͲ͵Ǣ ͳͺͲ͹ǢͳͺͲͻ ǢͳͺͳͲ Ǣ
    ͳͺͳͳǢͳͺͳʹǢͳͺͳͷȗǢͳͺͳ͹ȗǢͳͺʹ͵Ǣͳͺ͵͵Ǣͳͺ͵͵Ǣͳͺ͵ͷǢͳͺ͵͸Ǣ
    ͳͺ͵͹Ǣͳͺ͵͹ Ǣͳͺ͵͹Ǣͳͺ͵ͺǢͳͺͶͳǢͳͺͶͳǢͳͺͶͳǢͳͺͶ͵ǢͳͺͶ͵Ǣ
    ͳͺͷ͵ǢͳͺͷͶǢʹʹǢʹͶǢʹ͹Ǣ͵͵Ǣ͵͹Ǣ͵͹Ǣ͵ͻǢ͵ͻǢ ͶͳǢͶͶǢͶͶ Ǣ
    ͶͶǢͶ͹ Ǣ͸ͳ Ǣ͸ʹʹǢ͸Ͷ Ǣ͸ͶǢ͸ͶǢ͹ͳ Ǣ͹ͳǢ͹ͳǢ
    ͳ͹ͺ͹̴ ͳ͹ͺͺ†‡Ž‹•
    BRCA2ȋ̴ͲͲͲͲͷͻȌ ͳǫǢͳ͵ͻ͵ǢͳͶʹ ǢͳͷͻǢ ͳ͹͵Ǣͳ͹ͶǢͳͻͳ Ǣͳͻ͸ǢʹͲ͸Ǣʹͳͳ ǢʹͳͳǢ
    ʹʹͷͺǢʹ͵͵͸Ǣʹ͵͵͸ Ǣʹ͵͵͸Ǣʹ͵͵͸Ǣʹͷ͵ʹǢʹ͸ͲʹǢʹ͸ʹ͸Ǣ ʹ͸ʹ͹ Ǣ
    ʹ͸Ͷ͹Ǣʹ͸ͷ͵Ǣʹ͸ͷͻǢʹ͸ͷͻǢʹ͸͸͵Ǣʹ͸͹ͲǢ ʹ͸͹ͷǢʹ͸ͻͷǢʹ͹ʹʹǢʹ͹ʹ͵Ǣ
    ʹ͹ʹ͵ Ǣʹ͹ʹ͵ Ǣ ʹ͹ͶͺǢʹ͹ͺͶǢʹͺʹͻǢʹͺͶʹǢʹͻͳͺǢ͵ͲͲʹǢ͵Ͳ͵ͻǢ
    ͵ͲͷʹǢ͵ͲͻͷǢ͵ͳ͸͹Ǣ͵͵Ͷʹ
    CCND1ȋ̴Ͳͷ͵Ͳͷ͸Ȍ ʹͺ͹ Ǣʹͺ͸Ǣʹͺ͸ Ǣʹͺ͹Ǣʹͺ͹Ǣʹͺ͹Ǣʹͺ͹
    CDK4ȋ̴ͲͲͲͲ͹ͷȌ ʹʹǢʹʹǢʹͶ ǢʹͶǢʹͶǢʹͶ
    CDK6ȋ̴ͲͲͳʹͷͻȌ ͺ͹
    CDKN2Aȋ̴Ͳͷͺͳͻͷǡ ͳͲȗǢ ͳͲͳǢͳͲͺ ǢͳͲͺ ǢͳͲͺǢͳͲͺǢͳͲͺǢͳͳͲȗǢͳͳͶ ǢͳͳͶǢͳͳͶǢ
    ̴ͲͲͲͲ͹͹Ȍ ͳʹȗǢͳʹͲȗǢ ͳʹͷǢͳʹͺǢͳʹͻȗǢͳͷȗǢ ʹ͵ǢʹͶǢʹ͹†‡ŽǢʹͺ̴͵͵†‡ŽǢ
    ʹͻ̴͵Ͷ†‡ŽǢ͵ʹ̴͵͹†‡ŽǢ ͵ͷ̴͵͸†‡ŽǢ ͵ͷ†‡ŽǢ͵͸̴͵ͻ†‡Ž‹•Ǣ͵͹̴ͶͶ†‡Ž‹•Ǣ
    ͵ͻ̴Ͷʹ†‡ŽǢͶͶȗǢͶͺǢͷͲȗǢͷͲ Ǣͷ͵ ǢͷͺȗǢͷͻ Ǣ͸ͲǢ͸ͳȗǢ ͸͹Ǣ͸ͻȗǢ͸ͻǢ
    ͹ͳǢ͹ͶǢ͹ͶǢ͹ͶǢ ͹ͷǢͺͲȗǢͺͲǢͺͳǢ ͺ͵Ǣ ͺ͵Ǣ ͺ͵Ǣ ͺ͵Ǣ ͺ͵Ǣ
    ͺͶ ǢͺͶǢͺͶǢͺͶǢͺ͹ǢͺͺȗǢͺͺǢͻ͹ Ǣͻ͹ǢͻͺǢ ͻͺ
    CTNNB1ȋ̴ͲͲͳͻͲͶȌ ͵ʹǢ͵ʹ Ǣ͵ʹ Ǣ͵ʹǢ͵ʹǢ͵ʹǢ͵͵Ǣ͵͵Ǣ͵͵ Ǣ͵͵Ǣ͵͵Ǣ͵͵Ǣ ͵ͶǢ
    ͵ͶǢ ͵ͶǢ ͵ͶǢ͵͹Ǣ͵͹Ǣ͵͹ Ǣ͵͹Ǣ͵͹ǢͶͳǢͶͳ ǢͶͳǢͶͷǢͶͷ ǢͶͷǢ
    ͶͷǢͶͷ
    EGFRȋ̴ͲͲͷʹʹͺȌ ͳͲ͸ͻǢͳͲͺ ǢͳͲͺǢͳͳͶǢʹʹʹǢʹʹͻǢʹͷʹǢʹ͸͵ǢʹͺͻǢʹͺͻǢʹͺͻǢ
    ͵ʹͶǢ͵ʹͶǢ͵͵ͲǢͶͶͳǢͶͶͳ ǢͶͷͳǢͶ͸ͶǢ Ͷ͸ͷǢ Ͷ͸ͷǢͶ͸͹Ǣ ͶͻͳǢ
    ͶͻͳǢͶͻʹ ǢͶͻʹǢͷͶ͸Ǣͷͺ͹ Ǣͷͻ͸Ǣ ͷͻͺǢ ͷͻͺǢ͸ʹͶǢ͸͵ͺǢ͸ͶͷǢ
    ͸͹ͳǢ͸ͺͶ Ǣ͸ͻͳǢ͸ͻʹ Ǣ͹Ͳ͵Ǣ͹Ͳ͵Ǣ͹ͲͻǢ͹Ͳͻ Ǣ͹ͲͻǢ͹ͲͻǢ͹ͲͻǢ
    ͹ͳͲǢ͹ͳͺǢ͹ͳͺǢ ͹ͳͻǢ ͹ͳͻǢ ͹ͳͻǢ ͹ͳͻǢ ͹ͳͻǢ͹ʹͲǢ͹ʹʹǢ ͹ʹ͵Ǣ
    ͹ʹͶǢ͹ʹͷǢ͹ʹ͸Ǣ͹ʹ͹ Ǣ͹͵ͳȗǢ͹͵ͳǢ͹͵͵Ǣ͹͵ͶǢ͹͵ͶǢ ͹͵ͷǢ͹ͶʹǢ
    ͹ͶͷǢ͹Ͷ͸ Ǣ͹Ͷ͸Ǣ͹Ͷ͸Ǣ͹Ͷ͸Ǣ͹Ͷ͹Ǣ͹Ͷ͹ Ǣ͹Ͷ͹Ǣ͹Ͷ͹Ǣ͹ͶͻǢ͹ͷͲǢ
    ͹ͷͲǢ͹ͷͳ Ǣ͹ͷʹǢ͹ͷ͵Ǣ͹ͷͺ Ǣ͹͸ͳǢ͹͸ͳǢ͹͸ͷǢ͹͸ͺ Ǣ͹͸ͻǢ͹͸ͻǢ
    ͹͹ͳǢ ͹͹͵Ǣ ͹͹͵Ǣ͹͹ͶǢ͹͹ͶǢ͹͹͸ Ǣ͹͹͸Ǣ͹͹͸ Ǣ͹ͺ͵Ǣ͹ͺͶ Ǣ͹ͺͷǢ
    ͹ͻͲǢ͹ͻʹ Ǣ͹ͻʹ Ǣ͹ͻʹǢ͹ͻʹǢ͹ͻʹǢ ͹ͻ͸Ǣ ͹ͻ͸Ǣ ͹ͻ͸Ǣ ͹ͻ͸Ǣ͹ͻ͹Ǣ
    ͹ͻ͹Ǣ͹ͻ͹ Ǣ͹ͻ͹Ǣ͹ͻ͹ǢͺͲͳ ǢͺͲʹ ǢͺͲͶ ǢͺͲ͸Ǣ ͺͳͲǢͺͳͳ Ǣͺʹ͸Ǣ
    ͺʹ͸Ǣͺ͵ͳ Ǣͺ͵͵Ǣͺ͵ͶǢ ͺ͵ͷǢͺ͵͸Ǣͺ͵͹Ǣͺ͵ͺǢͺ͵ͺǢͺͶͶǢͺͷͳ Ǣ
    ͺͷͶǢͺͷͶǢͺͷͶ Ǣ ͺͷ͹ǢͺͷͺǢͺͷͺǢͺͷͺǢͺͷͻǢͺ͸ͳǢͺ͸ͳǢͺ͸ͳ Ǣ
    ͺ͸ͳǢͺ͸ͶǢͺ͸ͶǢͺ͸ͺ Ǣ ͺ͹ͲǢͺ͹ͳ ǢͺͺͶǢͺͻͳ

    ͻ͵‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Gene (Transcript ID) Reportable cDNA and Amino Acid Changes
    ERBB2ȋ̴ͲͲͶͶͶͺȌ ʹ͸ͷǢ ʹ͹ͻǢ ʹ͹ͻǢʹͺͲ ǢʹͺͲǢ ʹͻʹǢ ͵ͲͻǢ ͵ͲͻǢ͵ͳͲ Ǣ͵ͳͲǢ͵ʹͳ Ǣ
    ͸ͷ͵Ǣ͸ͷͻǢ ͸͸ͲǢ͸͹ͺǢ͸͹ͺǢ͹ʹ͸ Ǣ͹ʹ͸ Ǣ͹͵͵ Ǣ͹͵ͻǢ ͹Ͷ͸Ǣ͹ͷͷǢ
    ͹ͷͷǢ͹ͷͷǢ͹ͷͷǢ͹ͷͷ Ǣ͹ͷͷǢ͹ͷͷǢ͹ͷͷǢ͹͸ʹǢ͹͸ʹǢ ͹͸͹ Ǣ ͹͸͹Ǣ
    ͹͸ͻ Ǣ͹͸ͻǢ͹͸ͻǢ͹͸ͻǢ͹͹ͲǢ͹͹͵Ǣ ͹͹͸Ǣ ͹͹͸Ǣ ͹͹͸Ǣ ͹͹͸Ǣ͹͹͹Ǣ
    ͹͹͹Ǣ͹͹͹Ǣ͹ͺͲǢ͹ͻͶǢ͹ͻͺ Ǣ͹ͻͺǢͺͲͺǢͺʹͳǢͺʹ͹ǢͺͶʹ Ǣͺͷ͹Ǣ
    ͺ͸ʹǢͺ͸ʹ Ǣͺ͸͸Ǣͺ͸ͻǢ ͺ͹ͺǢͺͺͶǢͺͻ͸Ǣͺͻ͸ 
    ESR1ȋ̴ͲͲͳͳʹʹ͹ͶʹȌ ͵Ͳ͵Ǣ͵ͺͲǢ͵ͻʹ ǢͶ͵͸ǢͶ͸͵ǢͶ͸ͻǢͷͲ͵Ǣͷ͵ͶǢͷ͵ͷ Ǣͷ͵͸ Ǣͷ͵͸Ǣ
    ͷ͵͸Ǣͷ͵͸Ǣͷ͵͸ Ǣͷ͵͸Ǣͷ͵͹Ǣͷ͵͹Ǣͷ͵͹Ǣͷ͵͹ Ǣͷ͵͹Ǣͷ͵ͺ Ǣͷ͵ͺǢ
    ͷͻͶ
    FGFR1ȋ̴Ͳʹ͵ͳͳͲȌ ͳʹͷǢʹͷʹǢͷͳͷǢͷͶͶǢͷͶ͸ǢͷͶ͸Ǣͷ͹͹Ǣ͸ͷ͸Ǣ͸ͷ͸Ǣ͸ͺ͹
    FGFR2ȋ̴ͲͲͲͳͶͳȌ ͳͲͳǢʹͲ͵ǢʹͷʹǢʹͷʹǢʹͷ͵Ǣʹ͸ͺ†—’Ǣ ʹ͹͸Ǣ͵ͳͲǢ͵ʹͲǢ͵ͶʹǢ͵ͷͶǢ
    ͵͹Ͷ Ǣ͵͹ͷǢ͵ͺʹǢ͵ͺʹǢ͵ͺʹ Ǣ͵ͺ͵ǢͷʹͶǢͷ͵͸ Ǣͷ͵͹ Ǣͷ͵ͺ Ǣ ͷͶ͹Ǣ
    ͷͶͺǢͷͶͻ ǢͷͶͻǢͷͷͲǢͷ͸Ͷ Ǣͷ͸ͷǢ͸͵ͺǢ͸͵ͻǢ͸ͷͺǢ͸ͷͺǢ͸ͷͻǢ
    ͸ͷͻǢ͸ͷͻǢ͸͸ͲǢ͹͵ͳ
    FGFR3ȋ̴ͲͲͲͳͶʹȌ ʹͶͺǢʹͶͻǢ͵ʹʹǢ ͵͹ͲǢ͵͹͵Ǣ͵͹ͷǢ ͵ͺͲǢ͸ͶͺǢ͸ͷͲǢ͸ͷͲǢ͸ͷͲǢ
    ͸ͷͲǢ͸ͷͲǢ͸ͷͲǢ͸ͷͲ Ǣ ͸ͻͻ
    GNA11ȋ̴ͲͲʹͲ͸͹Ȍ ͳͺ͵ǢʹͲͻǢʹͲͻ
    GNAQȋ̴ͲͲʹͲ͹ʹȌ ͳͺ͵ǢʹͲͻǢʹͲͻǢʹͲͻǢͻ͸
    HNF1Aȋ̴ͲͲͲͷͶͷȌ ʹͻͳˆ•Ǣ ʹͻʹˆ•
    HRASȋ̴ͲͲͷ͵Ͷ͵Ȍ ͳͳ͹Ǣͳͳ͹Ǣ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳ͵†—’Ǣ ͳ͵Ǣ ͳ͵Ǣ ͳ͵Ǣ
    ͳ͵ǢͳͶ͸ǢͳͶ͸Ǣͷͻ ǢͷͻǢ͸ͳǢ͸ͳǢ͸ͳǢ͸ͳ 
    IDH1ȋ̴ͲͲͷͺͻ͸Ȍ ͳ͵ʹ
    IDH2ȋ̴ͲͲʹͳ͸ͺȌ ͳ͹ʹ Ǣͳ͹ʹǢͳ͹ʹǢͳ͹ʹ
    KITȋ̴ͲͲͲʹʹʹȌ ͶͶ͵ǢͶ͸͵ǢͶͻͲǢ ͷͲͶǢͷͲͷ ǢͷʹǢͷʹ Ǣ ͷʹʹǢͷ͵Ͳ ǢͷͷͲǢͷͷ͵Ǣ
    ͷͷ͵Ǣͷͷ͹ Ǣͷͷ͹Ǣͷͷ͹Ǣͷͷ͹ǢͷͷͺǢͷͷͺǢͷͷͺǢͷͷͺǢͷͷͻǢͷͷͻǢ
    ͷͷͻ Ǣͷ͸ͲǢͷ͸Ͳ Ǣͷ͸ͲǢͷ͸ͲǢͷ͸͸Ǣͷ͸ͻ Ǣͷ͹Ͳ Ǣͷ͹ʹǢͷ͹͸Ǣͷ͹ͺǢ
    ͷ͹ͺǢ͸͵ͶǢ͸͵ͷǢ͸ͶͳǢ͸ͶʹǢ͸ͶʹǢ͸ͶʹǢ͸Ͷ͵Ǣ͸Ͷ͹Ǣ ͸ͷ͵Ǣ͸ͷͶǢ
    ͸ͷͶǢ͸ͷͷǢ͸ͷͷǢ͸ͷͷǢ͸͹ͲǢ͸͹Ͳ Ǣ͸ͺͲǢ ͸ͻ͹Ǣ͹Ͳͻ Ǣ͹ͳ͸Ǣ͹Ͷ͸Ǣ
    ͹ͺ͵ǢͺͲͶǢͺͲͻ Ǣͺͳ͸ǢͺͳͶǢͺͳ͸ Ǣͺͳ͸ Ǣͺͳ͸Ǣͺͳ͸Ǣͺͳ͸Ǣͺͳ͸Ǣ
    ͺͳ͸ Ǣͺͳ͸ǢͺʹͲǢͺʹͲǢͺʹͲ ǢͺʹͲǢͺʹͲ ǢͺʹͲǢͺʹͲǢͺʹͳ Ǣͺʹʹ Ǣ
    ͺʹʹ ǢͺʹʹǢͺʹʹǢͺʹʹǢͺʹ͵ǢͺʹͷǢͺʹͻǢͺ͵ͺǢ ͺͶͳǢͺ͸Ͷ 
    KRASȋ̴ͲͲͶͻͺͷȌ ͳͲ†—’Ǣͳͳ̴ ͳʹ†—’Ǣͳͳ͸ Ǣͳͳ͹Ǣͳͳ͹ Ǣͳͳ͹ǢͳͳͻǢͳͳͻ Ǣ ͳʹǢ ͳʹǢ
    ͳʹǢ ͳʹ Ǣ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹ Ǣ ͳʹǢ ͳʹǢ ͳʹ̴ ͳ͵†—’Ǣ ͳ͵Ǣ ͳ͵Ǣ
    ͳ͵Ǣ ͳ͵Ǣ ͳ͵ Ǣ ͳ͵Ǣ ͳ͵Ǣ ͳ͵Ǣ ͳ͵ Ǣ ͳ͵†—’Ǣ ͳʹ̴ ͳ͵‹• ǢͳͶ ǢͳͶǢ
    ͳͶ͸ǢͳͶ͸ǢͳͶ͸ǢͳͶ͸ǢͳͺǢͳͻ ǢʹʹǢʹʹǢʹʹǢʹʹǢ ʹͶǢ͵͵Ǣ͵ͶǢ
    ͵ͶǢ ͵͸ǢͷǢͷǢͷͲ Ǣͷͺ ǢͷͻǢͷͻ ǢͷͻǢ ͸ͲǢ ͸ͲǢ͸ͳ Ǣ͸ͳǢ͸ͳǢ
    ͸ͳǢ͸ͳǢ͸ͳǢ͸ʹǢ͸ͷǢ͸ͷ Ǣ͹ͳ Ǣ͹ͳǢ͹ͶǢͻ͹
    MAP2K1ȋ̴ͲͲʹ͹ͷͷȌ ͳͳͳǢ ͳͳͳǢ ͳͳͳǢ ͳͳͳǢ ͳͳͳǢ ͳͳͻǢͳʹͲǢͳʹͳǢͳʹͳǢͳʹͶǢͳʹͶǢ
    ͳʹͶǢ ͳʹͺǢ ͳʹͺǢʹͲ͵ǢʹͳͳǢʹͳͷǢʹ͸ͶǢ͵ͺʹ Ǣ ͷ͵Ǣ ͷ͵ Ǣ ͷ͵Ǣ ͷ͵Ǣ
    ͷ͵Ǣ ͷ͵Ǣͷ͸Ǣͷ͹Ǣͷ͹Ǣͷ͹Ǣ͸͹Ǣ ͻͻ
    MAP2K2ȋ̴Ͳ͵Ͳ͸͸ʹȌ ͳʹͷǢͳʹͺǢͳʹͺǢͳ͵Ͷ Ǣͳ͵ͶǢʹͳͷǢ ͷ͹Ǣ ͷ͹Ǣ ͷ͹Ǣ͸Ͳ
    METȋ̴ͲͲͲʹͶͷȌ ͳͲͲ͵ǢͳͲͲ͵ ǢͳͲͲ͵ǢͳͲͲͻǢͳͲͳͲ ǢͳͲͳͲǢͳͲͳͲǢͳͲʹͳǢͳͲʹͳ Ǣ
    ͳͲʹͳǢͳͲ͹ͲǢͳͲ͹ͲǢͳͲ͹ͲǢͳͲͺͺǢͳͲͺͺǢͳͲͺͺǢͳͲͻʹ ǢͳͲͻʹǢ
    ͳͲͻͶǢ ͳͲͻͶǢ ͳͲͻͶǢ ͳͳͲ͸ǢͳͳͳͲ ǢͳͳͳͲǢ ͳͳͳʹǢ ͳͳͳʹǢ ͳͳͳʹǢ
    ͳͳͳͺǢ ͳͳʹͶǢͳͳ͵ͳǢͳͳͶͻǢ ͳͳ͸͵Ǣͳͳ͹͵ Ǣ ͳͳͺͳǢͳͳͺͺǢͳͳͻͳ Ǣ
    ͳͳͻͷǢͳͳͻͷ ǢͳʹͲ͸Ǣͳʹͳ͵Ǣ ͳʹͳͺ ǢͳʹʹͲ Ǣͳʹʹͺ ǢͳʹʹͺǢͳʹ͵ͲǢͳʹ͵Ͳ Ǣ
    ͳʹ͵ͲǢͳʹ͵Ͳ Ǣͳʹ͵ͲǢͳʹ͵ͷǢͳʹ͵ͷ Ǣͳʹ͵ͺ ǢͳʹͶ͸ ǢͳʹͶ͸ǢͳʹͶ͸Ǣ
    ͳʹͶͺǢͳʹͶͺ ǢͳʹͶͺǢͳʹͶͺǢͳʹͷͲǢͳʹͷ͵Ǣͳʹͷ͵ Ǣͳʹ͸ʹǢͳʹ͸ͺ Ǣ
    ͳʹ͸ͺ
    MTORȋ̴ͲͲͶͻͷͺȌ ͳͶ͵͵ǢͳͶͷʹǢͳͶͷ͸ ǢͳͶͷ͸ǢͳͶͷͻǢͳͶ͸ͲǢͳͶͺ͵ ǢͳͶͺ͵ǢͳͶͺ͵Ǣ
    ͳ͹ͻͻǢ ͳͺͺͺǢ ͳͺͺͺ Ǣ ͳͺͺͺǢͳͻ͹͹Ǣͳͻ͹͹ Ǣͳͻ͹͹ǢʹͲͳͶǢʹʹͳͷ ǢʹʹͳͷǢ
    ʹʹͳͷǢʹʹ͵ͲǢʹͶʹ͹ǢʹͶʹ͹Ǣ ʹͷͲͲ Ǣ ʹͷͲͲ

    ͻͶ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Gene (Transcript ID) Reportable cDNA and Amino Acid Changes
    NFE2L2ȋ̴ͲͲ͸ͳ͸ͶȌ ʹͶǢʹͶǢʹͶǢ ʹͺǢʹͻ ǢʹͻǢʹͻǢ͵Ͳ Ǣ͵ͲǢ ͵ͳǢ ͵ͳǢ ͵ͳǢ͵ʹ Ǣ
    ͵Ͷ Ǣ͵ͶǢ͸͵Ǣ͸͵Ǣ͹͹ Ǣ͹͹ Ǣ͹ͻǢ͹ͻǢ͹ͻǢͺͲǢͺͲǢͺͲǢ ͺͳǢ
    ͺͳǢ ͺͳǢ ͺͳǢͺʹǢͺʹǢͺʹ Ǣͺʹ
    NRASȋ̴ͲͲʹͷʹͶȌ ͳͳ͹Ǣ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳʹǢ ͳ͵Ǣ ͳ͵Ǣ ͳ͵Ǣ ͳ͵Ǣ ͳ͵Ǣ
    ͳ͵ǢͳͶ͸Ǣͳ͹ͲǢͳͺǢʹʹǢ͵͵ǢͷǢͷͲ Ǣͷͺ Ǣͷͻ ǢͷͻǢ ͸ͲǢ͸ͳ Ǣ
    ͸ͳǢ͸ͳǢ͸ͳǢ͸ͳȗǢ͸ͳǢ͸ͳǢ͸ͷ
    NTRK1ȋ̴ͲͲʹͷʹͻȌ ͵ͶʹǢͶ͵ͶǢͷ͸Ͷ Ǣͷ͹͵Ǣͷͺ͵Ǣ ͷͺͻǢ ͷͻͷǢ ͷͻͷǢ͸ͲͺǢ ͸Ͷ͸ Ǣ ͸͸͹Ǣ
    ͸͸͹Ǣ͸͹ͻ Ǣ͸ͻʹǢ͸ͻʹ 
    NTRK3ȋ̴ͲͲͳͲͳʹ͵͵ͺȌ ͸ʹ͵Ǣ ͸ͻ͸
    PDGFRAȋ̴ͲͲ͸ʹͲ͸Ȍ ʹʹͻǢʹ͹ͷ ǢʹͺͺǢͶ͸ͻǢͷ͵͸Ǣͷ͵͸ǢͷͷͷǢͷͷ͸Ǣͷ͸ͳǢͷ͸ͳǢͷ͸͵Ǣ
    ͷ͸ͺǢͷ͹͹Ǣͷ͹ͻǢ͸͵͵Ǣ ͸ͷͲǢ͸ͷͺǢ͸ͷͻǢ͸ͷͻǢ͸ͷͻǢ͹Ͷͺ ǢͺͶͳǢ
    ͺͶʹ ǢͺͶʹǢ ͺͶͷǢͺͶ͸ǢͺͶͺǢͺͶͻǢͺͶͻǢ ͺͷ͵Ǣͺͷͻ
    PIK3CAȋ̴ͲͲ͸ʹͳͺȌ ͳͲʹͳǢͳͲʹͳ ǢͳͲʹͷǢͳͲʹͷǢͳͲʹͻǢͳͲͶǢͳͲͶ͵ ǢͳͲͶ͵ǢͳͲͶ͵Ǣ
    ͳͲͶ͵ǢͳͲͶͶǢͳͲͶͶǢ ͳͲͶ͹Ǣ ͳͲͶ͹Ǣ ͳͲͶ͹Ǣ ͳͲͶ͹Ǣ ͳͲͶͻǢ ͳͲͶͻǢ
    ͳͲ͸Ǣ ͳͲ͸Ǣ ͳͲ͸ǢͳͲ͸ͺˆ•ǢȗͳͲ͸ͻˆ•ǢͳͲͺ ǢͳͳͲǢͳͳͳǢͳͳͳǢͳͳͳǢ
    ͳͳͺǢ͵ͶͶ Ǣ͵ͶͶǢ͵ͶͶǢ͵Ͷͷ Ǣ͵ͶͷǢ͵ͶͷǢ͵ͶͷǢ͵Ͷͷ Ǣ͵ͷͲ Ǣ͵͸ͷǢ
    ͵͹ͺǢ͵͹ͺǢ͵ͺǢ͵ͺ Ǣ͵ͺ Ǣ͵ͺǢ͵ͺǢ͵ͻǢͶͳͺǢͶʹͲ ǢͶʹͲǢͶͶͻǢ
    Ͷͷ͵ǢͶͷ͵ǢͶͷ͵ǢͶͷ͵Ǣͷ͵ͻǢͷͶʹǢͷͶʹ ǢͷͶʹǢͷͶʹǢͷͶʹǢͷͶͷǢ
    ͷͶͷǢͷͶͷ ǢͷͶͷǢͷͶͷǢͷͶͷǢͷͶ͸ ǢͷͶ͸ǢͷͶ͸ǢͷͶ͸ǢͷͶ͸ǢͷͶ͸Ǣ
    ͷͶͻǢͷ͹ͺ Ǣͷ͹ͻǢ͸ͲͶǢ ͹ͲͳǢ͹ʹ͸Ǣ͹ʹ͸ǢͺͳǢͺͺǢͻͲͳ Ǣ ͻͳͶǢ
    ͻ͵Ǣͻ͵
    RAF1ȋ̴ͲͲʹͺͺͲȌ ͳͶ͵ǢͳͶ͵Ǣʹͷ͹Ǣʹͷ͹ǢʹͷͻǢʹͷͻ ǢʹͷͻǢʹ͸ͲǢʹ͸ͳǢʹ͸ͳǢʹ͸ʹǢ
    ʹ͸͵Ǣ͵͸ͺǢ͵ͻ͹ǢͶʹ͹ Ǣ ͶͶͺǢ͸ͳ͵Ǣ͹͵
    RETȋ̴ͲʹͲͻ͹ͷȌ ͵͹͵Ǣ͸Ͳ͸Ǣ͸ͳͺǢ͸ʹͺ̴͸͵͵†‡ŽǢ͸ʹͺ̴͸͵͵†‡Ž‹• Ǣ͸ʹͻ̴͸͵ͳ†‡Ž‹• Ǣ
    ͸͵Ͳ̴͸͵ͳ†‡ŽǢ͸͵ͳ̴͸͵͵†‡Ž‹•Ǣ͸͵ͳ̴͸͵͵†‡Ž‹•Ǣ͸͵ͳ̴͸͵͵†‡Ž‹•Ǣ
    ͸͵ʹ̴͸͵͵†‡ŽǢ͸͵ʹ̴͸͵͸†‡Ž‹•Ǣ͹͵Ͳ Ǣ͹͵ͲǢ͹͵ʹǢ͹͵ͺǢ͹͹ͺ ǢͺͲͶǢͺͲͶǢ
    ͺͲͶǢͺͲ͸ǢͺͲ͸ǢͺͲ͹Ǣ ͺͳͲǢ ͺͳͲǢ ͺͳͲǢͺ͵͵Ǣ ͺͷʹǢͺ͹ͳ Ǣͺ͹͵Ǣ
    ͺͺ͵ ǢͻͲͶ ǢͻͳͺǢͻʹʹ Ǣ ͻͶͻǢ ͻͻͺǢ
    RHEBȋ̴ͲͲͷ͸ͳͶȌ ͵ͷǢ͵ͷǢ͵ͷ 
    ROS1ȋ̴ͲͲʹͻͶͶȌ ͳͻʹͳ ǢͳͻͷͳǢͳͻ͹ͶǢͳͻ͹ͻǢͳͻ͹ͻǢͳͻͺͳ‹•Ǣͳͻͺʹ ǢͳͻͺʹǢͳͻͺ͸ Ǣ
    ͳͻͺ͸ǢͳͻͻͲ Ǣ ͳͻͻͶǢʹͲͲͳǢʹͲͲ͵ Ǣ ʹͲͲͶǢ ʹͲͲͶ Ǣ ʹͲͲͶǢ ʹͲͲͻǢʹͲʹͺǢ
    ʹͲʹͲǢ ʹͲʹͶǢ ʹͲʹͶǢʹͲʹ͸ǢʹͲʹ͸ǢʹͲ͵͵Ǣ ʹͲ͵ʹǢʹͲ͵͵Ǣ ʹͲ͹ͷǢ ʹͲ͹ͷ Ǣ
    ʹͲ͹ͷǢʹͲͺͻǢ ʹͳͲͳǢʹͳͳʹǢʹͳͳ͵ Ǣʹͳͳ͸Ǣʹͳʹ͹ȗǢʹͳʹͺǢʹͳ͵Ͷ Ǣ
    ʹͳͷͷǢʹʹʹ͵ȗǢʹʹʹͶ
    SMAD4ȋ̴ͲͲͷ͵ͷͻȌ ʹͶͷȗǢ͵͵ͲǢ͵͵Ͳ Ǣ͵͵ͲǢ͵ͷͳ Ǣ͵ͷͳ Ǣ͵ͷͳǢ͵ͷͳǢ͵ͷ͸Ǣ͵ͷ͸Ǣ͵ͷ͸Ǣ
    ͵ͷͺȗǢ͵͸ͳǢ͵͸ͳ Ǣ͵͸ͳǢ͵͸ͳǢ͵͸ͳ Ǣ ͵ͺ͸Ǣ ͵ͺ͸Ǣ ͵ͺ͸ǢͶͳʹȗǢͶͶͷȗǢ
    Ͷͻ͵ǢͶͻ͵ǢͶͻ͵ ǢͷͳͷȗǢͷʹͶǢͷʹͶǢͷʹͶǢͷ͵͹Ǣͷ͵͹ Ǣͷ͵͹
    SMOȋ̴ͲͲͷ͸͵ͳȌ ʹͶͳǢʹͺͳǢ͵ʹͳǢ͵ʹͳǢ͵ʹͶǢ ͶͲͺǢͶͳʹ ǢͶ͹͵ ǢͶ͹͵ǢͶ͹͵Ǣ Ͷͻ͹Ǣ
    ͷ͵͵Ǣͷ͵ͷǢͷ͵ͷǢͷ͸ʹ
    TERTȋ̴ͳͻͺʹͷ͵Ȍ ǤǦͳʹͶεǢ ǤǦͳͶ͸εǢ ǤǦͷ͹εǢ ǤǦͶͷ εǢ ǤǦʹ͵͸ εǢ ǤǦͳʹͶεǢ ǤǦͳ͵ͺεǢ ǤǦͳ͵ͻεǢ
    ǤǦͳ εǢ ǤǦͷͶε

    Table 67. Guardant360 CDx Reportable Alterations Based on Exons and Codons
    Gene (Transcript ID) Alteration Type Exon Codon
    BRAFȋ̴ͲͲͶ͵͵͵Ȍ †‡Ž ͳʹǢͳͷ Ǧ
    EGFRȋ̴ͲͲͷʹʹͺȌ  Ǧ Ͷ͵͸ǢͶͶͳǢͶͶʹǢͶͷͳǢͶ͸ͶǢͶ͸ͷǢ
    Ͷ͸͸ǢͶͺͻǢͶͻͳǢͶͻʹǢͶͻ͹ǢͶͻͺ
    EGFRȋ̴ͲͲͷʹʹͺȌ †‡Ž ͳͺǢͳͻǢʹͲ Ǧ
    ERBB2ȋ̴ͲͲͶͶͶͺȌ †‡Ž ͳͻǢʹͲ Ǧ
    ESR1ȋ̴ͲͲͳͳʹʹ͹ͶʹȌ †‡Ž ͺǢͳͲ Ǧ
    ESR1ȋ̴ͲͲͳͳʹʹ͹ͶʹȌ ȋ‹••‡•‡  Ǧ ͵ͳͲǦͷͶ͹

    ͻͷ‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Gene (Transcript ID) Alteration Type Exon Codon
    KITȋ̴ͲͲͲʹʹʹȌ †‡Ž ŽŽ‹Ǧˆ”ƒ‡ǡ‡š Ž—†‹‰ Ǧ
    •’Ž‹ ‡•‹–‡
    METȋ̴ͲͲͲʹͶͷȌ ǡ †‡Ž ͳͶ Ǧ
    METȋ̴ͲͲͲʹͶͷȌ  ͳͻ Ǧ
    MYCȋ̴ͲͲʹͶ͸͹Ȍ  Ǧ ͹Ͷǡͳ͸ͳǡʹͷͳ
    NFE2L2ȋ̴ͲͲ͸ͳ͸ͶȌ  Ǧ ʹͶǡʹ͸ǡʹ͹ǡʹͺǡʹͻǡ͵Ͳǡ͵ͳǡ͵ʹǡ
    ͵Ͷǡ͹͹ǡ͹ͻǡͺͲǡͺͳǡͺʹ
    PDGFRAȋ̴ͲͲ͸ʹͲ͸Ȍ †‡Ž ŽŽ‹Ǧˆ”ƒ‡ǡ‡š Ž—†‹‰ Ǧ
    •’Ž‹ ‡•‹–‡
    PIK3CAȋ̴ͲͲ͸ʹͳͺȌ †‡Ž ʹǢͺ Ǧ
    ROS1ȋ̴ͲͲʹͻͶͶȌ †‡Ž ͵͹ Ǧ

    Table 68. Guardant360 CDx Reportable Alterations Based on Loss of Function


    Gene (Transcript ID) Reportable cDNA and Amino Acid Changes
    BRCA1ȋ̴ͲͲ͹ʹͻͶȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹ƒŽŽ‡š‘•Ǥ
    BRCA2ȋ̴ͲͲͲͲͷͻȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹ƒŽŽ‡š‘•Ǥ
    CDH1ȋ̴ͲͲͶ͵͸ͲȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹‡š‘•͵ǡͺǡƒ†ͻǤ
    GATA3ȋ̴ͲͲͳͲͲʹʹͻͷȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹‡š‘•ͷƒ†͸Ǥ
    MLH1ȋ̴ͲͲͲʹͶͻȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹‡š‘ͳʹǤ
    NF1ȋ̴ͲͲͳͲͶʹͶͻʹȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹‡š‘•ͳͳƒ†ʹͻǤ
    PTENȋ̴ͲͲͲ͵ͳͶȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹ƒŽŽ‡š‘•Ǥ
    STK11ȋ̴ͲͲͲͶͷͷȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹ƒŽŽ‡š‘•Ǥ
    TSC1ȋ̴ͲͲͲ͵͸ͺȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹‡š‘•ͳͷƒ†ʹ͵Ǥ
    VHLȋ̴ͲͲͲͷͷͳȌ ‘••‘ˆˆ— –‹‘ƒŽ–‡”ƒ–‹‘•ˆ‘—†‹ƒŽŽ‡š‘•Ǥ

    Table 69. Biomarker Rules for Companion Diagnostic Claims Reported by Guardant360 CDx
    Indication Biomarker Reportable Mutations
    ‘Ǧ•ƒŽŽ ‡ŽŽŽ—‰ EGFR‡š‘ͳͻ†‡Ž‡–‹‘•ǡͺͷͺǡƒ† š‘ͳͻ†‡Ž‡–‹‘•ǡͺͷͺǡƒ†͹ͻͲ
    ƒ ‡”ȋ  ͹ͻͲ
    EGFR‡š‘ʹͲ‹•‡”–‹‘• š‘ʹͲ‹•‡”–‹‘•
    KRAS ͳʹ ͳʹ
    ERBB2ȀHER2ƒ –‹˜ƒ–‹‰—–ƒ–‹‘• ͵ͳͲ Ǣ͵ͳͲǢ͸͹ͺǢ͹͵͵ Ǣ͹ͷͷǢ͹ͷͷǢ͹ͷͷǢ
    ȋ•ƒ†‡š‘ʹͲ‹•‡”–‹‘•Ȍ ͹ͷͷǢ͹ͷͷǢ ͹͸͹ Ǣ ͹͸͹Ǣ͹͸ͻ Ǣ͹͸ͻǢ͹͸ͻǢ
    ͹͹ʹ̴͹͹ͷ†—’Ǣ͹͹ͷ̴ ͹͹͸‹•Ǣ͹͹ͷ̴ ͹͹͸‹•Ǣ
    ͹͹ͷ̴ ͹͹͸‹•Ǣ ͹͹͸Ǣ ͹͹͸Ǣ ͹͹͸Ǣ
    ͹͹͸̴͹͹͹†‡Ž‹• Ǣ ͹͹͸̴͹͹͹‹•Ǣ
    ͹͹͸̴͹͹͹‹•Ǣ ͹͹͸̴͹͹͹‹• Ǣ ͹͹͸†‡Ž‹•Ǣ
    ͹͹͸†‡Ž‹•Ǣ͹͹͹Ǣ͹͹͹Ǣ͹͹͹̴ ͹͹ͺ‹• Ǣ
    ͹͹͹̴ ͹͹ͺ‹• Ǣ͹͹͹̴͹͹ͻ†—’Ǣ ͹͹ͺ̴͹ͺͲ†—’Ǣ
    ͹͹ͺ̴͹͹ͻ‹• Ǣ ͹͹ͺ̴͹͹ͻ‹•Ǣ ͹͹ͺ†—’Ǣ
    ͹͹ͻ̴͹ͺͲ‹• Ǣ͹ͺͲ̴͹ͺͳ‹• Ǣ͹ͻͺ ǢͺͶʹ Ǣ
    ͺ͸ʹ Ǣͺ͸ͻǢͺͻ͸Ǣͺͻ͸ 
    ”‡ƒ•– ƒ ‡” ESR1‹••‡•‡—–ƒ–‹‘•„‡–™‡‡ ‹••‡•‡—–ƒ–‹‘•„‡–™‡‡ ‘†‘•͵ͳͲƒ†ͷͶ͹
    ‘†‘•͵ͳͲǦͷͶ͹
    —–ƒ–‹‘•ˆ‘—†‹’ƒ–‹‡–•™‹–Š–Š‡ ‘””‡•’‘†‹‰‹†‹ ƒ–‹‘™‹ŽŽ„‡”‡’‘”–‡†‹ƒ–‡‰‘”›ͳƒ•ƒ ‘’ƒ‹‘†‹ƒ‰‘•–‹ 
    ȋšȌˆ‘”ƒ••‘ ‹ƒ–‡†–Š‡”ƒ’‹‡•ƒ•‹†‹ ƒ–‡†‹Table 1Ǥ

    ͻ͸‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    9. Additional Information
    ͻǤͳǤ ›„‘Ž•

    Manufacturer Date of Use By Batch Code Catalog Number Serial Number Biological Risk CE Marking
    Manufacture Of Conformity

    Sterilized by Do not Re-Use Consult Contents In Vitro Authorized Temperature Health


    Irradiation Instructions Sufficient for Diagnostic Representative Limitation Hazard
    For Use Number Medical in the
    Specified Device European
    Community

    Rx ONLY

    By Prescription
    Only
    

    10. References
    ‡‹Œ—ƒ‹Ǥ–ƒ–‹•–‹ ƒŽ ‘•‹†‡”ƒ–‹‘ƒ† ŠƒŽŽ‡‰‡•‹„”‹†‰‹‰•–—†›‘ˆ’‡”•‘ƒŽ‹œ‡†‡†‹ ‹‡ǤJ.
    Biopharma Stat.ȋʹͲͳͷȌǢʹͷǣ͵ͻ͹ǦͶͲ͹Ǥ

    ͻ͹‘ˆͻ͹
    ͲͳȀʹͲʹ͵  ǦͲͲͲ͵Ͳʹʹ  —ƒ”†ƒ–͵͸Ͳš‡ Š‹ ƒŽ ˆ‘”ƒ–‹‘
    
    Example Report

    NSCLC patient with EGFR exon 19 deletion


    (alteration below lowest MAF from clinical study)
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    EGFR exon 19 deletions  1


    DETECTED EGFR E746_A750del
    TAGRISSO® (osimertinib) is FDA-approved for this indication
    EGFR L858R NOT DETECTED
    EGFR T790M NOT DETECTED
    EGFR exon 20 insertions NOT DETECTED
    ERBB2/HER2 activating NOT DETECTED
    mutations (SNVs and exon 20
    insertions)
    KRAS G12C NOT DETECTED
    1The MAF for EGFR exon 19 detection for this patient is < 0.08%. Please refer below to Limitations section.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    NSCLC patient with EGFR L858R


    (alteration below lowest MAF from clinical study)
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    EGFR L858R  1
    DETECTED EGFR L858R
    TAGRISSO® (osimertinib) is FDA-approved for this indication
    EGFR T790M NOT DETECTED
    EGFR exon 19 deletions NOT DETECTED
    EGFR exon 20 insertions NOT DETECTED
    ERBB2/HER2 activating NOT DETECTED
    mutations (SNVs and exon 20
    insertions)
    KRAS G12C NOT DETECTED
    1The MAF for EGFR L858R detection for this patient is < 0.09%. Please refer below to Limitations section.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    NSCLC patient with EGFR T790M


    (alteration below lowest MAF from clinical study)
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    EGFR T790M  1
    DETECTED EGFR T790M
    TAGRISSO® (osimertinib) is FDA-approved for this indication
    EGFR L858R NOT DETECTED
    EGFR exon 19 deletions NOT DETECTED
    EGFR exon 20 insertions NOT DETECTED
    ERBB2/HER2 activating NOT DETECTED
    mutations (SNVs and exon 20
    insertions)
    KRAS G12C NOT DETECTED
    1The MAF for EGFR T790M detection for this patient is < 0.03%. Please refer below to Limitations section.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    NSCLC patient with EGFR exon 20 insertion


    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    EGFR exon 20 insertions DETECTED EGFR H773_V774insHPH


    RYBREVANT® (amivantamab-vmjw) is FDA-approved for this indication
    EGFR L858R NOT DETECTED
    EGFR T790M NOT DETECTED
    EGFR exon 19 deletions NOT DETECTED
    ERBB2/HER2 activating NOT DETECTED
    mutations (SNVs and exon 20
    insertions)
    KRAS G12C NOT DETECTED

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    NSCLC patient with an ERBB2 activating mutation (insertion)


    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    ERBB2/HER2 activating DETECTED ERBB2 A775_G776insYVMA


    mutations (SNVs and exon 20 ENHERTU® (fam-trastuzumab deruxtecan-nxki) is FDA-approved for this
    insertions)1 indication
    EGFR L858R NOT DETECTED
    EGFR T790M NOT DETECTED
    EGFR exon 19 deletions NOT DETECTED
    EGFR exon 20 insertions NOT DETECTED
    KRAS G12C NOT DETECTED

    1The MAF for ERBB2 exon 20 insertion for this patient is < 0.03%. Please refer below to Limitations section.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    NSCLC patient with an ERBB2 activating mutation (SNV)


    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    ERBB2/HER2 activating DETECTED ERBB2 V777L


    mutations (SNVs and exon 20 ENHERTU® (fam-trastuzumab deruxtecan-nxki) is FDA-approved for this
    insertions)1 indication
    EGFR L858R NOT DETECTED
    EGFR T790M NOT DETECTED
    EGFR exon 19 deletions NOT DETECTED
    EGFR exon 20 insertions NOT DETECTED
    KRAS G12C NOT DETECTED

    1The MAF for ERBB2 SNV for this patient is < 0.23%. Please refer below to Limitations section.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    NSCLC patient with KRAS G12C


    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    KRAS G12C DETECTED KRAS G12C


    LUMAKRAS™ (sotorasib) is FDA-approved for this indication
    EGFR L858R NOT DETECTED
    EGFR T790M NOT DETECTED
    EGFR exon 19 deletions NOT DETECTED
    EGFR exon 20 insertions NOT DETECTED
    ERBB2/HER2 activating NOT DETECTED
    mutations (SNVs and exon 20
    insertions)

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Non Small Cell Lung Cancer (NSCLC)
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    Breast cancer patient with ESR1 missense mutations


    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    Biomarker Status Additional Information

    ESR1 missense mutations DETECTED ESR1 H356D


    between codons 310-547 ORSERDU™ (elacestrant) is FDA-approved for this indication

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 missense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    Breast cancer patient with PIK3CA C420R


    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    No reportable alterations with companion diagnostic (CDx) claims

    Other Biomarkers Identified


    Results reported in this section are not prescriptive or conclusive for labeled use of any specific therapeutic product. See
    professional services section for additional information.

    ctDNA Biomarkers with Strong Evidence of Clinical Significance in ctDNA†


    Biomarker Status Additional Information
    PIK3CA Activating SNVs DETECTED PIK3CA C420R
    See professional services section for additional information
    †
    Please refer below to Performance Characteristics and Definitions sections for descriptions of categories.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    CRC patient with KRAS Q61R


    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Colorectal Cancer
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    No reportable alterations with companion diagnostic (CDx) claims

    Other Biomarkers Identified


    Results reported in this section are not prescriptive or conclusive for labeled use of any specific therapeutic product. See
    professional services section for additional information.

    Biomarkers with Evidence of Clinical Significance in Tissue and ctDNA†


    Biomarker Status Additional Information
    KRAS Activating SNVs DETECTED KRAS Q61R
    See professional services section for additional information
    †
    Please refer below to Performance Characteristics and Definitions sections for descriptions of categories.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Colorectal Cancer
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Colorectal Cancer
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    Melanoma patient with BRAF V600E


    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Melanoma
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    No reportable alterations with companion diagnostic (CDx) claims

    Other Biomarkers Identified


    Results reported in this section are not prescriptive or conclusive for labeled use of any specific therapeutic product. See
    professional services section for additional information.

    Biomarkers with Evidence of Clinical Significance in Tissue and ctDNA†


    Biomarker Status Additional Information
    BRAF V600E DETECTED BRAF V600E
    See professional services section for additional information
    †
    Please refer below to Performance Characteristics and Definitions sections for descriptions of categories.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Melanoma
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Bruce, Wayne (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Male
    
    Diagnosis: Melanoma
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Example Report

    Breast cancer patient with only Category 4 variant


    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    REPORTING PHYSICIAN
    Report Date: MAR-20-2017 Dougie Houser
    Receipt Date: MAR-04-2017 Center for People Who are Sick and Want to Get Better
    Collection Date: MAR-03-2017 123 Four St., Metropolis, NY, 12345, United States
    Ph: (808) 555-1234 | Fax: (808) 555-9999
    Specimen: Blood
    Additional Recipient: N/A
    Status:
    
    FINAL

    Companion Diagnostic
    No reportable alterations with companion diagnostic (CDx) claims

    Other Biomarkers Identified


    Results reported in this section are not prescriptive or conclusive for labeled use of any specific therapeutic product. See
    professional services section for additional information.

    Other Biomarkers with Potential Clinical Significance


    Clinical significance has not yet been established for biomarkers in this section. See the professional services section for
    additional information.

    – BRAF V600K

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    
    Page 1 of 3
     
     
    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com  LBL-000301 R2
    
    Page 2 of 3
     
     
    Wayne, Joey (A62106)
    Patient MRN: 987654321 | DOB: JAN-01-1976 | Sex: Female
    
    Diagnosis: Breast Cancer
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:855.698.8887 / F:888.974.4258 / Contact: clientservices@guardanthealth.com LBL-000301 R2
    Page 3 of 3 
     
     
    Blank Results Report
    Last Name, First Name (Acession ID)
    Patient MRN: NNNNNN | DOB: MMM-DD-YYYY | Sex: [Male/Female]
    
    Diagnosis: [Cancer Type]
    

    REPORTING PHYSICIAN
    Report Date: MMM-DD-YYYY First and Last Name
    Receipt Date: MMM-DD-YYYY Site Name
    Collection Date: MMM-DD-YYYY Site Address
    Ph: (xxx) xxx-xxxx | Fax: (xxx) xxx-xxxx
    Specimen: Blood
    Additional Recipient: First and Last Name
    Status:
    
    [Status]

    Companion Diagnostic
    Biomarker Status Additional Information

    [Insert biomarker as appropiate] 


    [Dynamic] {n} placed after EGFR exon 19 deletion, L858R, and/or T790M

    [Dynamic] (n)The MAF for EGFR exon 19 detection for this patient is <0.08%. Please refer below to Limitations section.
    [Dynamic] (n)The MAF for EGFR L858R for this patient is <0.09%. Please refer below to Limitations section.
    [Dynamic] (n)The MAF for EGFR T790M for this patient is <0.03%. Please refer below to Limitations section.

    Other Biomarkers Identified


    Results reported in this section are not prescriptive or conclusive for labeled use of any specific therapeutic product. See
    professional services section for additional information.

    ctDNA Biomarkers with Strong Evidence of Clinical Significance in ctDNA†


    Biomarker Status Additional Information

    [Insert alteration as appropriate]

    †
    Please refer below to Performance Characteristics and Definitions sections for descriptions of categories.

    Biomarkers with Evidence of Clinical Significance in Tissue and ctDNA†


    Biomarker Status Additional Information
    [Insert alteration as appropriate]

    †
    Please refer below to Performance Characteristics and Definitions sections for descriptions of categories.

    Other Biomarkers with Potential Clinical Significance


    Clinical significance has not yet been established for biomarkers in this section. See the professional services section for
    additional information.

    – [Insert alteration as appropriate]

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:xxx.xxx.xxxx / F:xxx.xxx.xxxx / Contact: xxxxxxxxxx@xxxxxxxxxx.xxx LBL-000301 R2
    
    Page 1 of 3
     
     
    Last Name, First Name (Acession ID)
    Patient MRN: NNNNNN | DOB: MMM-DD-YYYY | Sex: [Male/Female]
    
    Diagnosis: [Cancer Type]
    

    Intended Use
    Guardant360® CDx is a qualitative next generation sequencing-based in vitro diagnostic device that uses targeted high throughput hybridization-based capture technology
    for detection of single nucleotide variants (SNVs), insertions and deletions (indels) in 55 genes, copy number amplifications (CNAs) in two (2) genes, and fusions in four (4)
    genes. Guardant360 CDx utilizes circulating cell-free DNA (cfDNA) from plasma of peripheral whole blood collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs).
    The test is intended to be used as a companion diagnostic to identify patients who may benefit from treatment with the therapies listed in Table 1 in accordance with the
    approved therapeutic product labeling.

    Table 1. Companion Diagnostic Indications


    Indication Biomarker Therapy

    Non-small cell lung cancer EGFR exon 19 deletions, L858R, and T790M* TAGRISSO® (osimertinib)
    (NSCLC)
    EGFR exon 20 insertions RYBREVANT® (amivantamab-vmjw)

    ERBB2/HER2 activating mutations (SNVs and exon 20 insertions) ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    KRAS G12C LUMAKRAS™ (sotorasib)

    Breast cancer ESR1 misssense mutations between codons 310-547 ORSERDU™ (elacestrant)

    A negative result from a plasma specimen does not assure that the patient’s tumor is negative for genomic findings. Patients who are negative for the biomarkers listed in
    Table 1 should be reflexed to tissue biopsy testing for Table 1 biomarkers using an FDA-approved tumor tissue test, if feasible.
    *The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for T790M
    plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy cannot be
    obtained.
    Additionally, the test is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology
    for cancer patients with any solid malignant neoplasm. The test is for use with patients previously diagnosed with cancer and in conjunction with other laboratory and
    clinical findings.
    Genomic findings other than those listed in Table 1 are not prescriptive or conclusive for labeled use of any specific therapeutic product.
    Guardant360 CDx is a single-site assay performed at Guardant Health, Inc.

    Warnings and Precautions


    – Alterations reported may include somatic (not inherited) or germline (inherited) alterations. The assay filters germline variants from reporting except for pathogenic
    BRCA1, BRCA2, ATM, and CDK12 alterations. However, if a reported alteration is suspected to be germline, confirmatory testing should be considered in the
    appropriate clinical context.
    – The test is not intended to replace germline testing or to provide information about cancer predisposition.
    – Somatic alterations in ATM and CDK12 are not reported by the test as they are excluded from the test's reportable range.
    – Genomic findings from cfDNA may originate from circulating tumor DNA (ctDNA) fragments, germline alterations, or non-tumor somatic alterations, such as clonal
    hematopoiesis of indeterminate potential (CHIP).
    – Allow the tube to fill completely until blood stops flowing into the tube. Underfilling of tubes with less than 5 mL of blood (bottom of the label indicates 5 mL fill when
    tube is held vertically) may lead to incorrect analytical results or poor product performance. This tube has been designed to fill with 10 mL of blood.

    Limitations
    – For in vitro diagnostic use.
    – For prescription use only. This test must be ordered by a qualified medical professional in accordance with clinical laboratory regulations.
    – The efficacy of TAGRISSO (osimertinib) has not been established in the EGFR T790M plasma-positive, tissue-negative or unknown population and clinical data for
    T790M plasma-positive patients are limited; therefore, testing using plasma specimens is most appropriate for consideration in patients from whom a tumor biopsy
    cannot be obtained.
    – TAGRISSO efficacy has not been established in patients with EGFR exon 19 deletions < 0.08% MAF, in patients with EGFR L858R < 0.09% MAF, and in patients with
    EGFR T790M < 0.03% MAF.
    – RYBREVANT efficacy has not been established in patients with EGFR exon 20 insertions < 0.02% MAF.
    – LUMAKRAS efficacy has not been established in patients with KRAS G12C biomarkers < 0.11% MAF.
    – ENHERTU efficacy has not been established in patients with ERBB2 exon 20 insertions < 0.03% MAF and in patients with ERBB2 SNVs < 0.23% MAF.
    – ORSERDU efficacy has not been established in patients with ESR1 missense mutations < 0.03% MAF.
    – The test is not intended to be used for standalone diagnostic purposes.
    – The test is intended to be performed on specific serial number-controlled instruments by Guardant Health, Inc.
    – A negative result for any given variant does not preclude the presence of this variant in tumor tissue.
    – Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking into consideration all applicable
    information concerning the patient's condition, such as patient and family history, physical examinations, information from other diagnostic tests, and patient
    preferences, in accordance with the standard of care.
    – ctDNA shedding rate may be lower in patients with primary central nervous system (CNS) tumors.

    Performance Characteristics
    Please refer to product label, www.guardant360cdx.com/technicalinfo. Clinical Performance has not been established for biomarkers in categories 2, 3A, 3B and 4.
    Guardant360 CDx is indicated to report the following SNVs (AKT1, ALK, APC, AR, ARAF, ATM#, BRAF, BRCA1##, BRCA2##, CCND1, CDH1, CDK4, CDK6, CDK12#,
    CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC,
    NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL), Indels (ALK, AKT1, APC, ATM#,
    BRAF, BRCA1##, BRCA2##, CDH1, CDK12#, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS , KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET,
    ROS1, STK11, TSC1, VHL), Fusion (ALK , NTRK1, RET, ROS1), and Amplifications (ERBB2, MET).
    #
    Reporting is enabled for pathogenic germline alterations only. Somatic alterations will not be reported. | ##Reporting is enabled for both germline and somatic alterations.
    
    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:xxx.xxx.xxxx / F:xxx.xxx.xxxx / Contact: xxxxxxxxxx@xxxxxxxxxx.xxx LBL-000301 R2
    
    Page 2 of 3
     
     
    Last Name, First Name (Acession ID)
    Patient MRN: NNNNNN | DOB: MMM-DD-YYYY | Sex: [Male/Female]
    
    Diagnosis: [Cancer Type]
    

    Definition of Categories
    The test report includes genomic finding reported in the following categories:
    Prescriptive use
    Clinical Analytical
    Category for Therapeutic Comments
    Performance Performance
    Product
    Category 1: Companion Diagnostic ctDNA biomarkers linked to the safe and effective use of the
    (CDx) corresponding therapeutic product, for which Guardant360 CDx has
    Yes Yes Yes
    demonstrated clinical performance shown to support therapeutic
    efficacy and strong analytical performance for the biomarker.
    Category 2: ctDNA Biomarkers with ctDNA biomarkers with strong evidence of clinical significance
    Strong Evidence of Clinical Significance presented by other FDA-approved liquid biopsy companion
    No No Yes
    in ctDNA diagnostics for which Guardant360 CDx has demonstrated analytical
    reliability but not clinical performance.
    Category 3A: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: strong analytical professional guidelines for which Guardant360 CDx has
    No No Yes
    validation using ctDNA demonstrated analytical performance including analytical accuracy,
    and concordance of blood-based testing to tissue-based testing for
    the biomarker.
    Category 3B: Biomarkers with Evidence ctDNA biomarkers with evidence of clinical significance presented
    of Clinical Significance in tissue by tissue-based FDA-approved companion diagnostics or
    supported by: analytical validation No No Yes professional guidelines for which Guardant360 CDx has
    using ctDNA demonstrated minimum analytical performance including analytical
    accuracy.
    Category 4: Other Biomarkers with ctDNA biomarkers with emergent evidence based on peer-reviewed
    Potential Clinical Significance publications for genes/variants in tissue, variant information from
    No No Yes well- curated public databases, or in-vitro pre-clinical models, for
    which Guardant360 CDx has demonstrated minimum analytical
    performance.
    

    Testing performed at: Guardant Health


    Laboratory Director: Martina Lefterova, MD PhD | CLIA ID: 05D2070300 | CAP #: 8765297 | 505 Penobscot Drive Redwood City, CA, 94063, United States

    TM
    Guardant Health, Inc. / 505 Penobscot Drive, Redwood City, CA 94063, United States
    FDA-Approved Content
    T:xxx.xxx.xxxx / F:xxx.xxx.xxxx / Contact: xxxxxxxxxx@xxxxxxxxxx.xxx LBL-000301 R2
    Page 3 of 3 
     
    

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