CCO 2020 WCLC Downloadable 1

CCO Conference Highlights From the
2020 World Conference on Lung Cancer
CCO Independent Conference Coverage*

of the IASLC 2020 World Conference on Lung Cancer,
January 28-31, 2021
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.
Supported by educational grants from Amgen; Bristol-Myers Squibb; Ipsen; Janssen Pharmaceuticals,
NV; Jazz Pharmaceuticals, Inc.; Regeneron Pharmaceuticals, Inc.; Sanofi Genzyme; and Takeda
Oncology.
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Faculty
Shirish M. Gadgeel, MD Nicolas Girard, MD, PhD
Chief Professor
Division of Hematology/Oncology Université Paris-Saclay
Department of Internal Medicine Head of the Thorax Institute Curie-
Henry Ford Cancer Institute Montsouris
Henry Ford Health System Institut Curie
Detroit, Michigan Paris, France
Faculty Disclosures
The faculty reported the following financial relationships or relationships to products
or devices they have with commercial interests related to the content of this CME/CE
activity:
Shirish M. Gadgeel, MD, has disclosed that he has received consulting fees from
AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme,
Novartis, Pfizer, Roche/Genentech, and Takeda; fees for non-CME/CE services from
Merck Sharp & Dohme and Xcovery; and other financial or material support from
AstraZeneca and Roche/Genentech.
Nicolas Girard, MD, PhD, has disclosed that he has received consulting fees from
AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck Sharp &
Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, and Teva, and funds for research
support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen,
Merck Sharp & Dohme, Novartis, Pfizer, and Roche.
Non-Small-Cell Lung Cancer
Advances in the Treatment of
KRASG12C-Driven NSCLC
CodeBreaK 100: Sotorasib in KRAS p.G12C–Mutated
NSCLC
 Registrational phase II trial of highly selective irreversible KRASG12C inhibitor
Locally advanced/metastatic
NSCLC with KRAS p.G12C
mutation by central testing, Sotorasib Treatment
progressed on prior 960 mg oral QD until PD
standard therapy, no active
Radiographic scan every 6 wks
CNS metastases
through Wk 48, then every 12 wks
(N = 126)
 Primary endpoint: ORR by blinded  Secondary endpoints: DoR, DCR, TTR, PFS,
independent central review (RECIST OS, safety
v1.1)
 Exploratory endpoints: biomarker
evaluation (PD-L1; co-occurring mutations)
Li. WCLC 2020. Abstr PS01.07. NCT03600883. Slide credit: clinicaloptions.com
CodeBreaK 100: Baseline Characteristics
Sotorasib
 Total of 126 patients from 11 countries
Characteristic
(N = 126)
‒ 81% with progression on previous
Median age, yrs (range) 63.5 (37─80) platinum-based CT and PD-1/-L1 inhibitor
Smoking history, n  Never 6 (4.8)
(%)  Current or former 117 (92.9)
 Median follow-up: 12.2 mos
ECOG PS, n (%) ‒ Data cutoff: December 1, 2020
0 38 (30.2)
1 88 (69.8)
Previous lines of 1 54 (42.9)
systemic therapy, 2 44 (34.9)
n (%) 3 28 (22.2)
Previous systemic therapies, n (%)

 Platinum-based CT 113 (89.7)
 Anti-PD-1 or PD-L1 115 (91.3)
 Platinum-based CT + PD-1/-L1 inhibitors 102 (81.0)
Li. WCLC 2020. Abstr PS01.07. Slide credit: clinicaloptions.com

CodeBreaK 100: Efficacy Summary
Outcome
Sotorasib  > 80% of patients with disease control
(N = 124)
Confirmed ORR, % (95% CI)* ‒ 3 patients achieved CRs and 43 PRs
37.1 (28.6-46.2)
 CR 2.4
 PR  46% of responders remained on
34.7
 SD 43.5 treatment without progression as
 PD 16.1 of data cutoff
 Not evaluable 3.2
 Exploratory biomarker analyses:
DCR, % (95% CI) 80.6 (72.6-87.2)
Tumor shrinkage, % 81 (101 of 124 pts) ‒ Response across PD-L1 expression levels:
 Median best % shrinkage† 60 PD-L1 < 1%, 48%; PD-L1 1-49%, 39%;
PD-L1 ≥ 50%, 22%
Median DoR, mos (95% CI) 10.0 (6.9-11.1)
Median TTR, mos 1.4 ‒ Responses in STK11/KEAP1 comutated
Median PFS, mos (95% CI) 23%; single STK11 mutant 50%; single
6.8 (5.1-8.2)
KEAP1 mutant 14%; and double WT 42%
*Assessed by central review. †Among responders.

CodeBreaK 100: Safety
Sotorasib (N = 126)  Adverse events generally low grade
TRAE, n (%)
Any grade Grade 3 and manageable
Any 88 (69.8) 25 (19.8)  TRAEs led to d/c in 7.1% of patients,
Diarrhea 39 (31.0) 5 (4.0) dose modification in 22.2% of patients
Nausea 24 (19.0) 0
‒ 1 patient (0.8%) reported grade 4 TRAEs
ALT elevation 19 (15.1) 8 (6.3)
(pneumonitis and dyspnea)
AST elevation 19 (15.1) 7 (5.6)
Fatigue 14 (11.1) 0  No fatal TRAEs
Vomiting 10 (7.9) 0
Blood ALP elevation 9 (7.1) 1 (0.8)
Maculopapular rash 7 (5.6) 0

CodeBreaK 200: Sotorasib vs Docetaxel in Previously
Treated KRAS p.G12C–Mutated NSCLC
 Confirmatory, multicenter, randomized, open-label phase III study
Patients ≥ 18 yrs of age with

locally advanced and
Sotorasib
unresectable or metastatic
960 mg oral QD*
NSCLC with KRAS p.G12C Treatment
mutation confirmed by until PD
molecular testing; previously Docetaxel*
treated; ECOG PS 0/1
(N = 650) *21-day cycles.
 Primary endpoint: PFS  Secondary endpoints: OS, ORR, PRO, QoL,

(from baseline up to 6 mos) DoR, TTR, DCR
NCT04303780. Slide credit: clinicaloptions.com

EGFR Exon20ins NSCLC
Real-World Outcomes in Patients With Advanced
NSCLC by EGFR Alteration
 Comparative analysis of real-world outcomes  Study objectives
in patients with advanced NSCLC diagnoses
drawn from the Flatiron Health Analytic ‒ Prognostic value of exon20ins (n = 181) vs
Database (Jan 2011 - May 2020) L858R or exon19del (n = 2833); primary
endpoint, real-world OS
‒ Have EGFR exon20ins or common EGFR
‒ Predictive value of exon20ins (n = 76) vs
mutations (L858R or exon19del)
L858R or exon19del (n = 2749) for response to
‒ Treated with any TKI TKI treatment; primary endpoint, real-world
PFS
‒ Started treatment within 90 days of being
diagnosed with advanced disease ‒ Real-world patient characteristics, treatment
patterns, and outcomes for those with
exon20ins
 Baseline characteristics similar between

analysis arms except for male gender
(exon20ins, 43% male; L858R or exon19del,
33% male)
Girard. WCLC 2020. Abstr MA04.07. Slide credit: clinicaloptions.com
Real-World Outcomes in Patients With Advanced
NSCLC by EGFR Alteration: OS, PFS
Prognosis for EGFR Exon20ins vs EGFR L858R Predictive Value of EGFR Exon20ins vs EGFR L858R
or Exon19del: Real-World OS or Exon19del With TKI Therapy: Real-World PFS†
Common EGFR Exon20ins Common EGFR Exon20ins
100 77%
Median OS, mos 25.5 16.2 100 Median OS, mos 10.5 2.9
Patients (%)
Patients (%)
Adjusted HR: 1.75 72% Adjusted HR: 2.69
75 53% (95% CI: 1.5-2.1; P < .0001) 75 (95% CI: 2.1-3.6; P < .0001)
43%
50 57% 36% 50
25% 19% 25%
25 33%
23% 25 24%
17%
13% 13% 13% 9%
0 8% 0
0 6 12 18 24 30 36 42 48 54 60 0 6 12 18 24
Patients at Risk, n Mos Patients at Risk, n Mos *Stratified by line of therapy.
Common EGFR 2833 2245 1728 1313 943 675 494 354 262 198 139 Common EGFR 2749 1593 790 386 199
Exon20ins 181 120 77 53 30 22 16 11 6 5 3 Exon20ins 76 13 5 4 3
Risk With EGFR Exon20ins vs Risk With EGFR Exon20ins vs Percentage

Percentage Common EGFR Mutations on TKI
Common EGFR Mutations
Death (primary endpoint)* +75 Progression or death (primary endpoint) +169
Progression or death +93 Death +170
Shorter time to next treatment +60 Shorter time to next treatment +154
*5-yr survival for exon20ins is 8% vs 19% cEGFR. †Stratified by line of therapy.
Girard. WCLC 2020. Abstr MA04.07. Reproduced with permission. Slide credit: clinicaloptions.com
Real-World Outcomes in Patients With Advanced NSCLC
by EGFR Alteration: Treatment Patterns in Exon20ins
Median Real-World OS Median Real-World PFS Line 1 Line 2 Line 3
Treatment, %
by Therapy (95% CI) by Therapy (95% CI) (n = 181) (n = 115) (n = 64)
Line 1 Line 1 Platinum-based regimen
All patients All patients 61.3 23.5 21.9
16.2 5.1  Platinum doublet 27.6 11.3 7.8
(n = 181) (n = 181)  Platinum + IO
Platinum based Platinum based 17.7 7.0 3.1
17.4 6.6  Platinum + VEGF inhibitor 13.8 4.3 10.9
(n = 111) (n = 111)  Other combination 2.2 0.0 0.0
TKI alone
9.5
TKI alone
2.9  Platinum alone 0.0 0.9 0.0
(n = 39) (n = 39)
IO alone IO alone 3.1
12.1 TKI alone 21.5 21.7 10.9
(n = 16) (n = 16)
0 5 10 15 20 0 2.5 5.0 7.5 10.0 Other TKI combinations 0.6 0.0 0.0
Line 2* Line 2 IO alone
All patients All patients 8.8 28.7 21.9
13.3 (n = 115) 3.2
(n = 115) VEGF inhibitor alone
Platinum based Platinum based 0.6 9.6 10.9
14.2 5.0
(n = 27) (n = 27)
TKI alone Non-platinum chemotherapy 2.8 13.0 29.7
TKI alone 2.5
14 (n = 25)
(n = 25) Other 4.4 3.5 4.7
IO alone IO alone
9.1 2.3
(n = 33) (n = 33)
Non-Platinum 8.7
Non-Platinum
chemo (n = 15)
4.3  In patients with EGFR exon20ins, platinum-
chemo (n = 15)
0 5 10 15 20 0 2.5 5.0 7.5 based therapy was the most frequent first-
Months Months line treatment option
*OS determined from the start of line 2.
Girard. WCLC 2020. Abstr MA04.07. Reproduced with permission. Slide credit: clinicaloptions.com
CHRYSALIS: Amivantamab in Postplatinum NSCLC With
EGFR Exon20ins Mutations
 Phase I dose-escalation/expansion trial of amivantamab, an EGFR-MET bispecific antibody
Dose-escalation cohorts, Dose-expansion cohort D,
all with advanced NSCLC EGFR Exon20ins
Patients with Amivantamab at RP2D
Amivantamab 140-1750 mg
unresectable/metastatic NSCLC (1050 mg [< 80 kg] or 1400 mg [≥ 80 kg])
on Day 1, Day 8, then Q2W
who progressed on prior platinum- on Day 1, Day 8, then Q2W
based chemotherapy
(N = 460)
Median follow-up: 9.7 mos
Safety Population
(range: 1.1-29.3 mos)
Postplatinum exon20ins treated at RP2D
(N = 114)
 Primary endpoint: ORR
(per RECIST v1.1)
Efficacy Population
 Secondary endpoints: Postplatinum exon20ins with ≥ 3 disease
CBR, DoR, PFS, OS assessments at clinical cutoff
(n = 81)
Sabari. WCLC 2020. Abstr OA04.04. NCT02609776. Slide credit: clinicaloptions.com
CHRYSALIS: Baseline Characteristics
Efficacy Population Efficacy Population
Characteristic Characteristic
(n = 81) (n = 81)
Median age, yrs (range) 62 (42-84) Median prior lines of therapy, 2 (1-7)
Female, n (%) 48 (59) no. (range)
Race, n (%) Prior systemic therapy, n (%) 81 (100)
 Asian 40 (49)  Platinum doublet 81 (100)
 White 30 (37)  IO therapy 37 (46)
 Black 2 (3)  EGFR TKI 20 (25)
 Not reported/multiple 9 (11) • First generation 7 (9)
Nonsmoker/smoker, n (%) 43 (53)/38 (47) • Second generation 6 (7)
• Third generation 6 (7)
Median time from initial  Poziotinib 1 (1)
diagnosis, mos (range) 17 (1-130)
History of brain metastases, n (%) 18 (22)
Sabari. WCLC 2020. Abstr OA04.04. Slide credit: clinicaloptions.com

CHRYSALIS: Adverse Events and Patient Disposition
Safety Population (N = 114)
Safety Event, n (%)
TEAEs TRAEs
Any AE 113 (99) 112 (98)
Grade ≥ 3 AE 40 (35) 18 (16)
Serious AE 34 (30) 10 (9)
AE leading to death 8 (7) 0 (0)
AE leading to discontinuation 11 (10) 5 (4)
AE leading to dose reduction 15 (13) 15 (13)
AE leading to dose interruption* 40 (35) 24 (21)
*Excludes infusion-related reactions.
 Safety data cutoff: June 8, 2020

CHRYSALIS: Safety Summary
Safety Population (N = 114)  Safety profile consistent with AEs
AEs in ≥ 15% of Patients, n TEAE TRAE resulting from EGFR and MET pathway
(%)
All Grades Grade ≥ 3 All Grades Grade ≥ 3 inhibition
EGFR related  2% of patients discontinued treatment
 Rash* 98 (86) 4 (4) 98 (86) 4 (4)
 Paronychia 51 (45) 1 (1) 48 (42) 1 (1) due to rash
 Stomatitis 24 (21) 0 21 (18) 0
 Pruritus 19 (17) 0 19 (17) 0  12% of patients experienced diarrhea
(treatment related in 10%)
MET related
 Hypoalbuminemia 31 (27) 3 (3) 17 (15) 2 (2) ‒ Grade 1/2: 8.5%
 Peripheral edema 21 (18) 0 11 (10) 0
Other ‒ Grade 3: 3.5%
 Infusion-related reaction 75 (66) 3 (3) 75 (66) 3 (3)
 Constipation 27 (24) 0 7 (6) 0  Infusion-related reactions primarily
 Nausea 22 (19) 0 13 (11) 0
 Dyspnea 22 (19) 2 (2) 6 (5) 0 occurred during first infusion (94% of
 Fatigue
 ALT elevation
21 (18) 2 (2) 14 (12) 1 (1) cases), and did not impact ability to
17 (15) 1 (1) 14 (12) 1 (1)
*Includes all rash-related AEs.
receive subsequent treatments
CHRYSALIS: Response According to BICR
ORR (%) n/N ORR (95% Cl)
Efficacy Population Overall 32/81 40% (29-51)
Response (n = 81) Age, Yrs
< 65 21/48 44% (30-59)
ORR, % (95% CI) 40 (29-51) ≥ 65 11/33 33% (18-52)
Sex
CBR,* % (95% CI) 74 (63-83) Male 15/33 46% (28-64)
Female 17/48 35% (22-51)
Best response, n (%) Race†
Asian 17/40 43% (27-59)
 CR 3 (4) Non-Asian 14/32 44% (26-62)
 PR 29 (36) Baseline ECOG PS
 SD 39 (48) 0 14/26 54% (33-73)
 PD 8 (10)
≥1 18/55 33% (21-47)
 NE 1 (1)
Previous Lines of Tx
1 10/31 32% (17-51)
2 7/24 29% (13-51)
Median DoR, mos (95% CI) 11.1 (6.9-NR) ≥3 15/26 58% (37-77)
History of Smoking
Yes 13/38 34% (20-51)
No 19/43 44% (29-60)
History of Brain Metastases
*CBR = CR, PR, of SD at ≥ 2 disease assessments. Yes 7/18 39% (17-64)
†
Does not include 9 patients with race not reported and multiple race. No 25/63 40% (28-53)
0 20 40 60 80100
Sabari. WCLC 2020. Abstr OA04.04. Reproduced with permission. Slide credit: clinicaloptions.com
CHRYSALIS: Best ORR by Exon20Ins Region
Helical Region (n = 1) Near Loop (n = 54) Far Loop (n = 8) Not Detected by ctDNA (n = 18)
ORR: 100%; CBR: 100% ORR: 41%; CBR: 70% ORR: 25%; CBR: 75% ORR: 39%; CBR: 83%
80 Exon20ins Location:
Change From BL in Sum of Target
Helical region (762-766)

60 Near loop region (767-772)
Far loop region (773-775)
Lesion Diameter (%)
40 Not detected by ctDNA

20
0
-20
-40
-60
-80
-100 n = 80*
*1 patient discontinued prior to disease assessment and is not included in this analysis.
 25 different exon 20 insertion variants identified by NGS of ctDNA from 63 evaluable patient samples
CHRYSALIS: Responses Over Time
80 n = 80* Best Overall Response: CR PR SD PD  47% of patients (15/32)
NE/UNK
60 Treatment Status: Ongoing Completed/Discontinued remained on treatment at
Change From BL in Sum of Target
PD: Pre Post data cutoff

40
 63% of patients (20/32)
Lesion Diameter (%)
20
had responses ≥ 6 mos
0
 Median PFS: 8.3 mos
-20
(95% CI: 6.5-10.9)
-40
 Median OS: 22.8 mos
-60 (95% CI: 14.6-NR)
-80
-100
0 6 12 18 24
Mos
*1 patient discontinued prior to disease assessment and is not included in this analysis.
Phase I/II Trial of Mobocertinib in Advanced NSCLC With
EGFR Exon20ins
Phase II Dose Expansion: Mobocertinib 160 mg QD
Cohort 1: Refractory NSCLC with EGFR exon20ins,
no CNS mets that are both active and measurable EXCLAIM Extension Cohort:
previously treated advanced
Cohort 2: Refractory NSCLC with HER2 exon20ins/point NSCLC with EGFR exon20ins
Patients with muts, no CNS mets that are both active and measurable
advanced Cohort 3: Refractory NSCLC with EGFR or HER2 exon20ins or
Phase I Dose Current analysis:
NSCLC with point muts and active, measurable CNS mets
Escalation
EGFR exon 20  Patients with metastatic
insertions; 3 + 3 design Cohort 4: Tx-naive or tx-refractory NSCLC with
EGFR T790M or uncommon EGFR mutations NSCLC with EGFR
ECOG PS 0/1; exon20ins from EXCLAIM
≥ 1 prior line of Cohort 5: Refractory NSCLC with EGFR exon20ins extension cohort (n = 96;
therapy and prior response to EGFR TKI n = 86 with prior
(phase II only) platinum) and platinum-
Cohort 6: Tx-naive NSCLC with EGFR exon20ins
pretreated patient cohort
Cohort 7: Refractory non-NSCLC tumor types with
EGFR/HER2 muts
 Primary endpoint (phase II): ORR by RECIST v1.1  Key secondary endpoints (phase II):
safety, tolerability, PK, efficacy
Zhou. WCLC 2020. Abstr OA04.03. NCT02716116. Slide credit: clinicaloptions.com
Mobocertinib in NSCLC With EGFR Exon20ins:
Baseline Characteristics
PPP Cohort EXCLAIM Cohort
Characteristic (n = 114) (n = 96)
Median age, yrs (range) 60 (27-84) 59 (27-80)
Female, % 66 65
Asian/White/Black, % 60/37/3 69/29/2
ECOG PS 0/1, % 25/75 29/71
Never/current/former smoker, % 71/2/27 73/2/25
Median no. prior systemic tx (range) 2 (1-7) 1 (1-4)
No. prior systemic tx: 1/2/≥ 3, % 41/32/27 51/31/18
Prior platinum therapy, % 100 90
Prior TKI therapy, % 25 31
Prior immunotherapy, % 43 34
Zhou. WCLC 2020. Abstr OA04.03. Slide credit: clinicaloptions.com

Mobocertinib in NSCLC With EGFR Exon20ins: Efficacy
First Analysis (Data Cutoff: May 29, 2020) Updated Analysis (Data Cutoff: Nov 1, 2020)
Parameter PPP Cohort EXCLAIM Cohort PPP Cohort EXCLAIM Cohort
(n = 114) (n = 96) (n = 114) (n = 96)
Median time on treatment, mos (range) 7.0 (0-31) 6.5 (0-14) 7.4 (0-34.0) 6.8 (0-18.8)
Confirmed ORR per IRC, n (%) 30 (26) 22 (23) 32 (28) 24 (25)
Confirmed ORR per investigator, n (%) 40 (35) 31 (32) 40 (35) 31 (32)
Median DoR per IRC, mos 17.5 NE 17.5 NE
Median DoR per investigator, mos 13.9 NE 11.2 11.2
DCR per IRC, n (%) 89 (78) 73 (76) 89 (78) 73 (76)
DCR per investigator, n (%) 89 (78) 72 (75) 89 (78) 72 (75)
Median PFS per IRC, mos 7.3 7.3 7.3 7.3
Median PFS per investigator, mos 7.3 7.1 7.3 7.3
 Confirmed ORRs consistent across all  DoR per IRC of > 6 mos observed in 78%
subgroups* of PPP and 84% of EXCLAIM cohorts*
*In first analysis.

Mobocertinib in NSCLC With EGFR Exon20ins: Response
PPP Cohort EXCLAIM Cohort
100 100
PD SD PR PD SD PR
80
Target Lesion Diameter (%)
80
Target Lesion Diameter (%)

Change From BL in Sum of
Change From BL in Sum of

60 60
40 40
+20% +20%
20 20
0 0
-20 -30% -20 -30%
-40 -40
-60 -60
-80 -80
-100 Patients -100 Patients
 In PPP cohort, 82% of patients  In EXCLAIM cohort, 80% of

had reductions in target lesion patients had reductions in target
volume lesion volume
Zhou. WCLC 2020. Abstr OA04.03. Reproduced with permission. Slide credit: clinicaloptions.com
PFS and DoR in PPP Cohort
PFS (N = 114) DoR (n = 30)

100 Censored
100 Censored
DoR Probability (%)

30 responders
PFS Probability (%)
80 80
60 60
40 40
Number of events: 56 Number of events: 10
20 Median: 7.3 20 Median: 17.5
Min, max: 0, 24.0 Min, max: 1.8, 20.3
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 0 2 4 6 8 10 12 14 16 18 20 22 24
Mos Mos
Patients at Risk, n Patients at Risk, n
114 84 64 42 18 11 8 6 5 5 4 2 0 30 29 17 10 8 6 4 4 4 2 1 0
PFS and DoR in EXCLAIM Cohort
PFS (N = 96) DoR (n = 22)

100 Censored
100 Censored
DoR Probability (%)

22 responders
PFS Probability (%)
80 80
60 60
40 40
Number of events: 44
20 Median: 7.3 20 Median: not reached
Min, max: 0, 12.9 Min, max: 1.8, 11.1
0 0
0 2 4 6 8 10 12 0 2 4 6 8 10 12
Mos Mos
Patients at Risk, n Patients at Risk, n
96 71 53 33 10 3 1 22 20 10 5 3 1 0
Mobocertinib in NSCLC With EGFR Exon20ins: Safety
First Analysis  1 treatment-related death (cardiac
AE, n (%)
(Data Cutoff: May 29, 202) failure) in 1 platinum-treated
PPP Cohort EXCLAIM Cohort patient in EXCLAIM cohort*
(n = 114) (n = 96)
Any TRAE 113 (99) 95 (99)  Most common AEs leading to d/c*:
Grade ≥ 3 TRAE 53 (46) 39 (41)
‒ PPP cohort: nausea, 4%; diarrhea,
Serious TEAEs 52 (46) 39 (41)
4%; vomiting, 2%; decreased
AEs leading to
dose reduction 28 (25) 20 (21) appetite, 2%; stomatitis, 2%
AEs leading to d/c 19 (17) 10 (10) ‒ EXCLAIM cohort: nausea, 2%;
TRAEs leading to diarrhea, 2%
death 1 (1) 1 (1)
 Safety profile similar in updated
*In first analysis.
analysis (data cutoff: Nov 1, 2020)
Safety in PPP and EXCLAIM Cohorts
PPP Cohort (n = 114) EXCLAIM Cohort (n = 96)
Patients With Any Grade AE (%) Patients With Any Grade AE (%)
Diarrhea 90% Diarrhea 92%
Rash 45% Rash 45%
Paronychia 34% Paronychia 35%
Decreased appetite 32% Dry skin 30%
Nausea 32% Decreased appetite 29%
Dry skin 30% Nausea 28%
Vomiting 30% Increase creatinine 27%
Increased creatinine 25% Vomiting 26%
Stomatitis 22% Stomatitis 25%
Pruritus 20% Dermatitis acneiform 21%
0 20 40 60 80 100 0 20 40 60 80 100
 In both cohorts, diarrhea was the most common  Meaningful improvements in symptoms
grade 3/4 TRAE (occurring in scores for dyspnea (54.4%), coughing
≥ 5% of patients) (44.4%), and chest pain (38.8%)
‒ PPP cohort: 21%  Changes in symptom score evident in cycle 2
and maintained through treatment
‒ EXCLAIM cohort: 16%
EGFR Exon20ins NSCLC: Summary
 Real-world outcomes of EGFR exon20ins–mutant NSCLC: compared with common
EGFR mutations, patients with exon20ins have poorer prognosis[1]
‒ Higher risk of death (+75%) or increased risk of death or progression (+169% or +170%)
‒ Less benefit from TKIs and more likely to receive platinum-based CT in first-line
 CHRYSALIS: according to investigators, amivantamab has an acceptable safety profile
and shows activity in NSCLC harboring EGFR exon20ins[2]
‒ TRAEs primarily grade 1/2 in severity (16% grade ≥ 3)
‒ Antitumor activity observed in all patient subgroups and across insertion regions
 Phase I/II trial of mobocertinib: mobocertinib was active in patients with NSCLC
harboring EGFR exon20ins with evidence of durable responses[3]
1. Girard. WCLC 2020. Abstr MA04.07. 2. Sabari. WCLC 2020. Abstr OA04.04. 3. Zhou. WCLC 2020. Abstr OA04.03. Slide credit: clinicaloptions.com
Antibody–Drug Conjugates in Advanced NSCLC
DESTINY-Lung01: Novel ADC Trastuzumab Deruxtecan in
HER2-Overexpressing Metastatic NSCLC
 Multicenter, open-label phase II study
Current analysis
HER2
Overexpressing*
Cohort 1
Trastuzumab deruxtecan Interim Analysis of Cohort 1
Patients with 6.4 mg/kg Q3W (n = 49) (Data cutoff: May 31, 2020)
relapsed/refractory,
unresectable and/or  11 patients remained on tx
Trastuzumab deruxtecan  38 patients discontinued tx
metastatic Cohort 1a
5.4 mg/kg Q3W (n = 41) ‒ 22 due to PD
nonsquamous NSCLC, HER2 ‒ 9 due to AEs
and measurable Mutated ‒ 7 for other reasons†
Trastuzumab deruxtecan
disease by RECIST Cohort 2
6.4 mg/kg Q3W (n = 42) Median treatment duration: 18 wks
v1.1; ECOG PS 0/1
(range: 3.0-57.1 wks)
(N = 181)
Cohort 2 Trastuzumab deruxtecan
Expansion 6.4 mg/kg Q3W (n = 49)
*HER2 overexpression (IHC3+ or IHC2+; without known HER2 mutation) using locally archived tissue and confirmed centrally.
†Other reasons included death (n = 2; treatment unrelated), withdrawal of consent (n = 2), investigator decision (n = 2), or other (n = 1).
 Primary endpoint: ORR  Secondary endpoints: PFS, OS, DoR, DCR, safety,
and tolerability
Nakagawa. WCLC 2020. Abstr OA04.05. NCT03505710. Slide credit: clinicaloptions.com
Interim Analysis of DESTINY-Lung01 in
HER2-Overexpressing Cohort 1: Baseline Characteristics
Cohort 1* Characteristic Cohort 1*
Median age, yrs (range) 63 (37-85) Other gene abnormality status, n (%)
 < 65 yrs, n (%) 27 (55.1)  EGFR/ALK/ROS1/BRAF 3 (6.1)
 ≥ 75 yrs, n (%) 2 (4.1)  No EGFR/ALK/ROS1/BRAF 14 (28.6)
 Not reported 32 (65.3)
Female, n (%) 19 (38.8)
Region, n (%) Presence of CNS metastases, % 17 (34.7)
 Asia 12 (24.5) Prior therapies, % 49 (100)
 North America 19 (38.8)  Platinum based 45 (91.8)
 Europe 18 (36.7)  Anti–PD-1/PD-L1 36 (73.5)
 Docetaxel 12 (24.5)
ECOG PS 0/1, n (%) 14 (28.6)/35 (71.4)
HER2 IHC status, n (%) Median previous lines of therapy (range) 3 (1-8)
 IHC 3+ 10 (20.4)
 IHC 2+ 39 (79.6)
*Full analysis set data.

Nakagawa. WCLC 2020. Abstr OA04.05. Slide credit: clinicaloptions.com
HER2-Overexpressing Cohort 1: Efficacy Summary
IHC 3+ IHC 2+ Overall
Parameter
(n = 10) (n = 39) (n = 49)
Confirmed ORR, n (%; 95% CI)
2 (20.0; 2.5-55.6) 10 (25.6; 13.0-42.1) 12 (24.5; 13.3-38.9)
 CR 0 (2.6) (2.0)
 PR 2 (20.0) (23.1) (22.4)
 SD 6 (60.0) (41.0) (44.9)
 PD 1 (10.0) (25.6) (22.4)
 Not evaluable 1 (10.0) (7.7) (8.2)
DCR, n (%; 95% CI) 8 (80.0; 44.4-97.5) 26 (66.7; 49.8-80.9) 34 (69.4; 54.6-81.8)
Median DoR, mos (95% CI) 6.0 (NE-NE) 5.8 (3.2-NE) 6.0 (3.2-NE)
*Full analysis set data.

HER2-Overexpressing Cohort 1: Safety Summary
TEAEs,* n (%) Cohort 1 Cohort 1
(n = 49) TEAEs,* n (%)
(n = 49)
Any, 49 (100) TEAE of grade ≥ 3 (> 15%)
 Drug related 44 (89.8)  Decreased neutrophil count 10 (20.4)
Grade ≥ 3 36 (73.5) TEAEs associated with dose d/c†
 Drug related 27 (55.1)  Pneumonitis 5 (10.2)
Serious 22 (44.9) TEAES associated with dose reduction†
 Drug related 8 (16.3)  Decrease neutrophil count 5 (10.2)
 Fatigue 4 (8.2)
Associated with dose d/c 11 (22.4)  Nausea
 Drug related 3 (6.1)
6 (12.2)
Associated with dose reduction TEAEs associated with dose interruption†
17 (34.7)
 Drug related 16 (32.7)  Decrease neutrophil count 5 (10.2)
 Nausea 3 (6.1)
Associated with dose interruption 26 (53.1)
 Drug related 17 (34.4) TEAE grade 5‡/drug related 7 (14.3)/1 (2.0)
*Relationship to study drug determined by investigator.  Median treatment duration was 18 wks
†
Most commonly occurring in more than 2 patients. ‡TEAEs of grade 5: (range: 3.0-57.1 wks)
PD (n = 4), hydrocephalus, pneumonitis, and bronchospasm (1 each).
HER2-Overexpressing Cohort 1: AEs of Special Interest
Drug-Related ILD,* n (%) Cohort 1 Adjudicated drug-related ILD events*
(n = 49)
 Median time to onset of ILD was 64.5 days
Any 8 (16.3) (range: 2-126 days)
 Grade 1 2 (4.1)
 Grade 2 3 (6.1) ‒ All had drug withdrawn
 Grade 3 0 ‒ 3 patients recovered (grade 1, 1; grade 2, 2) and
 Grade 4 0
2 had not recovered (grade 1, 1; grade 2, 1) by
 Grade 5 3 (6.1)
data cutoff
 Steroid treatment was used in patients with
grade 2 (n = 3) and grade 5 (n = 3) ILD
Medical history of patients with grade 5 ILD events ‒ Steroids initiated 5 days after event of ILD
 Patient 1 : pulmonary embolism, productive cough,
†
reported by investigator
dyspnea, pleural effusion, lobectomy, and 4 previous  4/8 patients had previously received immune
lines of therapy checkpoint inhibitors treatment
 Patient 2†: cough, dyspnea, pleural effusion,
pulmonary embolism, and 5 previous lines of therapy
 Patient 3†: dyspnea, SLE without lung involvement, *Determined by adjudicating committee based on 44 preferred terms.
TTP, and 1 previous line of therapy †
Previously treated with immune checkpoint inhibitor.

TROPION-PanTumor01: Datopotamab Deruxtecan in
Advanced NSCLC
 First-in-human, dose-expansion phase I study of datopotamab deruxtecan, a
TROP2-directed antibody–drug conjugate with a topoisomerase 1 inhibitor payload
Patients ≥ 18 yrs (US) or DOSE EXPANSION
≥ 20 yrs (Japan) of age with Current analysis
DOSE ESCALATION
relapsed/refractory
Datopotamab deruxtecan Patients with NSCLC§
advanced/metastatic NSCLC, Datopotamab deruxtecan
 4 mg/kg Q3W (n = 50) (n = 175) treated with
unselected for TROP2* 0.27-10.0 mg/kg Q3W‡
 6 mg/kg Q3W (n = 50) 4-, 6-, or 8-mg/kg
expression, with measurable (n = 63)
 8 mg/kg Q3W (n = 80) dose
disease by RECIST v1.1, and
ECOG PS 0/1
(N = 350†)
 Primary endpoints: MTD, safety,  Secondary endpoints: efficacy and PK

and tolerability
*Pretreatment tumor tissue was required for retrospective analysis of TROP2 expression. †TNBC cohort 6 mg/kg enrolling; cohorts in other tumor
types may be added. ‡MTD stablished at 8 mg/kg Q3W. §Enrollment complete.
Spira. WCLC 2020. Abstr OA03.03. NCT03401385. Slide credit: clinicaloptions.com

TROPION-PanTumor01, Dose-Expansion Cohort (NSCLC):
Datopotamab Deruxtecan
Characteristic
4 mg/kg (n = 50) 6 mg/kg (n = 45) 8 mg/kg (n = 80)
Male, n (%) 27 (54) 26 (58) 41 (51)
Median age, yrs (range) 61 (35-82) 62 (45-76) 64 (31-84)
Region: US/Japan, n (%) 29 (58)/21 (42) 36 (80)/9 (20) 63 (79)/17 (21)
ECOG PS 0, n (%) 21 (42) 8 (18) 16 (20)
Nonsquamous histology, n (%) 41 (82) 40 (89) 70 (88)
≥ 3 prior lines of therapy, n (%) 25 (50) 26 (58) 51 (64)
Previous systemic treatment, n (%)
 Immunotherapy 42 (84) 35 (78) 70 (88)
 Platinum-based chemotherapy 44 (88) 43 (96) 78 (98)
 Tyrosine kinase inhibitor 10 (20) 6 (13) 14 (18)
History of brain metastases, n (%) 19 (38) 15 (33) 32 (40)
EGFR mutations, n (%) 8 (16) 3 (7) 15 (19)
Spira. WCLC 2020. Abstr OA03.03. Slide credit: clinicaloptions.com

Safety and Patient Disposition
Datopotamab Deruxtecan  Median follow-up: 7.4 mos
(range: 0.1-21.7)
Characteristic 4 mg/kg 6 mg/kg 8 mg/kg
(n = 50) (n = 45) (n = 80)  TEAEs primarily nonhematologic:
Discontinued study treatment, n (%) nausea/vomiting, stomatitis,
23 (46) 23 (51) 61 (76) alopecia, fatigue, decreased appetite,
 Due to progression 17 (34) 18 (40) 38 (48)
 Due to adverse event constipation, infusion-related
2 (4) 3 (7) 12 (15)
reactions
Median relative dose intensity, % 99.7 98.6 93.9
‒ Grade ≥ 3 stomatitis and mucosal
Treatment-emergent adverse event, n (%) inflammation more frequent with
 Grade ≥ 3 48 (96) 41 (91) 79 (99) 8-mg/kg vs 4-mg/kg or 6-mg/kg dose
 Treatment related 11 (22) 17 (38) 45 (56)
─ Grade ≥ 3 43 (86) 35 (78) 76 (95)  Treatment-related ILD in 8% of
 Serious 5 (10) 7 (16) 27 (34) patients: 1 each at 4 mg/kg and 6
─ Treatment related 9 (18) 16 (36) 38 (48)
4 (8) 4 (9) 16 (20) mg/kg; 12 at 8 mg/kg (including 3
 Associated with death patients with grade 5)
─ Treatment related 4 (8) 1 (2) 7 (9)
1 (2) 0 (0) 2 (3)
 Rate of d/c due to AEs was higher in
8-mg/kg vs 4-mg/kg or 6-mg/kg dose

Efficacy
Datopotamab Deruxtecan
Efficacy Outcome
4 mg/kg (n = 40) 6 mg/kg (n = 39) 8 mg/kg (n = 80)
ORR, n (%) 9 (23) 8 (21) 20 (25)
 Confirmed CR/PR, n (%) 7 (18) 6 (15) 19 (24)
 Unconfirmed CR/PR, n (%) 2 (5) 2 (5) 1 (1)
DCR, n (%) 29 (73) 26 (67) 64 (80)
PD, n (%) 6 (15) 8 (21) 7 (9)
Median PFS, mos (95% CI) 4.3 (2.0-NE) 8.2 (1.5-11.8) 5.4 (4.1-7.1)
 Consistent PK throughout 3 treatment cycles at each dose

‒ Half-life 4.6 days for 6-mg/kg dose, supporting Q3W dosing regimen

Antibody–Drug Conjugates in Advanced NSCLC:
Summary
 DESTINY-Lung01: trastuzumab deruxtecan showed promising early efficacy in
heavily pretreated, HER2-overexpressing NSCLC[1]
‒ ORR: 24.5%; similar ORR between HER2 expression of IHC3+ or 2+; DCR: 69.4%
‒ Consistent safety profile; need to monitor and manage drug-related ILD
 TROPION-PanTumor01: datopotamab deruxtecan showed manageable safety
profile and promising antitumor activity in heavily pretreated population of
advanced NSCLC[2]
‒ Better safety profile with 4-mg/kg and 6-mg/kg doses vs 8-mg/kg dose
‒ Phase III TROPION-LUNG01 trial evaluating 6-mg/kg dose vs docetaxel in previously
treated advanced NSCLC now open for enrollment[3]
1. Nakagawa. WCLC 2020. Abstr OA04.05. 2. Spira. WCLC 2020. Abstr OA03.03. 3. NCT04656652 Slide credit: clinicaloptions.com
Key Immunotherapy Studies in
Advanced NSCLC
Interdependence of KRAS and TP53 Mutations in
Predicting Response to ICIs in NSCLC
 Meta-analysis of cohorts investigated interrelation of mutations in KRAS and TP53
in predicting ICI treatment efficacy in EGFR/ALKWT nonsquamous NSCLC (N = 1129)
‒ 8 cohorts of patients treated in a clinical trial or real-world setting
‒ Patients could have received either or both PD-1/PD-L1 inhibitors and a CTLA-4 inhibitor
‒ PD-1/PD-L1 inhibitors: atezolizumab, pembrolizumab, nivolumab
‒ CTLA-4 inhibitor: ipilimumab
 Current analysis evaluated ORR, PFS, OS in KRAS-WT, KRAS-mut, TP53-WT,

TP53-mut, and KRAS/TP53-comutated subgroups
Li. WCLC 2020. Abstr OA07.06. Slide credit: clinicaloptions.com

KRAS and TP53 Mutations in Predicting ICI Efficacy:
Cohort n* Regimen Lines of Therapy Setting Outcome
3DMed 37 Anti–PD-1/PD-L1 First to subsequent Real world ORR, PFS, OS

SNCC 41 Anti–PD-1/PD-L1 First to subsequent Real world ORR, PFS
POPLAR/OAK 496 Atezolizumab vs docetaxel Second/third Clinical trial ORR, PFS, OS
Rizvi-34 27 Pembrolizumab Not mentioned Clinical trial ORR, PFS
Rizvi-240 179 Anti–PD-1/PD-L1 or combined First to subsequent Clinical trial and ORR, PFS
with anti–CTLA-4 real world
MSKCC-75 51 Nivolumab + ipilimumab Not mentioned Clinical trial ORR, PFS
Van Allen 37 Anti–PD-1/PD-L1 Not mentioned Not mentioned ORR, PFS, OS
Anti–CTLA-4, anti–PD-1/PD-L1 Clinical trial and
MSKCC-350 261 Not mentioned OS
or combination real world
*Number of EGFR/ALKWT nonsquamous patients.

KRAS and TP53 Mutations in Predicting ICI Efficacy:
Efficacy Analysis
 TP53 mutation associated with better ORR, PFS in patients with mutated but not WT KRAS
 KRAS mutation associated with better ORR, PFS in patients with mutated but not WT TP53
ORR PFS OS
Totality Variable
RR (95% CI) P Value HR (95% CI) P Value HR (95% CI) P Value
All TP53 mut vs TP53 WT 1.94 (1.31-2.87) .001 0.72 (0.55-0.95) .019 1.21 (0.98-1.50) .071
All KRAS mut vs KRAS WT 1.54 (1.02-2.32) .040 0.82 (0.56-1.19) .295 1.01 (0.70-1.47) .947
KRAS mut TP53 mut vs TP53 WT 2.86 (1.46-5.57) .002 0.47 (0.32-0.68) < .001 0.75 (0.51-1.12) .159
KRAS WT TP53 mut vs TP53 WT 1.53 (0.92-2.56) .104 0.91 (0.65-1.27) .566 1.47 (1.14-1.91) .003
TP53 mut KRAS mut vs KRAS WT 1.98 (1.17-3.35) .011 0.66 (0.47-0.93) .017 0.73 (0.51-1.04) .078
TP53 WT KRAS mut vs KRAS WT 1.28 (0.61-2.71) .518 1.04 (0.60-1.79) .885 1.19 (0.79-1.77) .338
All TP53/KRAS comutants 2.59 (1.63-4.12) < .001 0.58 (0.43-0.79) .001 0.86 (0.62-1.18) .356
vs others

KRAS and TP53 Mutations in Predicting ICI Efficacy: PFS
 TP53/KRAS comutations were associated with better immunotherapeutic but not chemotherapeutic
PFS; individual mutations showed no PFS benefit
 In the POPLAR/OAK trials, TP53/KRAS comutation predicted PFS benefit with atezolizumab over
docetaxel, independent of tumor mutational burden, PD-L1 expression, clinicopathology, or
immunotherapy-related mutations
Meta-Cohort PFS POPLAR/OAK PFS (Docetaxel)
Mutation(s)
n ORR, % Median PFS, Mos n ORR, % Median PFS, Mos
TP53 + KRAS 76 50.0 10.48 13 7.7 2.86

TP53 209 23.4 3.10 82 11.0 2.89
KRAS 101 16.7 2.77 15 13.3 2.86
Wild type 238 14.3 3.23 134 18.7 4.30
P value P < .001 P = .032

KEYNOTE-598: First-line Pembrolizumab ± Ipilimumab
for Metastatic NSCLC With PD-L1 TPS ≥ 50%
 Double-blind, randomized phase III study
Stratified by ECOG PS (0 vs 1), histology (squamous vs
nonsquamous), and region (East Asia vs others)
Patients with untreated stage IV NSCLC; Pembrolizumab 200 mg Q3W for ≤ 35 doses +
ECOG PS 0/1; Ipilimumab 1 mg/kg Q6W for ≤ 18 doses
no actionable EGFR/ALK aberrations; (n = 284)
PD-L1 TPS ≥ 50%*;
no untreated CNS mets; ≥ 1 lesion Pembrolizumab 200 mg Q3W for ≤ 35 doses +
measurable per RECIST v1.1 Placebo Q6W for up to 18 doses
(N = 568) (n = 284)
*Assessed centrally using the PD-L1 IHC 22C3 pharmDx assay.
 Primary endpoints: OS and PFS per RECIST v1.1 by BICR

 Key secondary endpoints: ORR and DoR per RECIST v1.1 by BICR, safety
Boyer. WCLC 2020. Abstr PS01.09. Slide credit: clinicaloptions.com
KEYNOTE-598: Baseline Characteristics
Characteristic Pembrolizumab + Ipilimumab Pembrolizumab + Placebo

(n = 284) (n = 284)
Male, n (%) 202 (71.1) 191 (67.3)
Enrolled in East Asia, n (%) 32 (11.3) 31 (10.9)
ECOG PS 1, n (%) 183 (64.4) 180 (63.4)
Former/current smoker, n (%) 255 (89.8) 259 (91.2)
Squamous, n (%) 77 (27.1) 81 (28.5)
Nonsquamous histology, n (%) 207 (72.9) 203 (71.5)
Brain metastases, n (%) 31 (10.9) 29 (10.2)

KEYNOTE-598: Response
Pembrolizumab + Ipilimumab Pembrolizumab + Placebo
Outcome
(n = 284) (n = 284)
ORR, % (95% CI) 45.4 (39.5-51.4) 45.4 (39.5-51.4)
Best response, n (%)
 CR
 PR 13 (4.6) 8 (2.8)
 SD 116 (40.8) 121 (42.6)
 PD 70 (24.6) 73 (25.7)
 Not evaluable 51 (18.0) 44 (15.5)
 Not available 6 (2.1) 6 (2.1)
28 (9.9) 32 (11.3)
DoR*
 Median, mos 16.1 17.3
 12-mo rate, % 60.9 65.8
*Reported using 129 for each arm.

KEYNOTE-598: OS and PFS
Pembrolizumab + Pembrolizumab +
Outcome Ipilimumab Placebo HR (95% CI)
(n = 284) (n = 284)
Median OS, mos 21.4 21.9
 12-mo rate, % 63.6 67.9
1.08 (0.85-1.37; P = .74)
 Patients with event, % 48.2 47.5
 RMST at 24 mos, mos 16.09 16.61
 RMST at maximum time, mos 18.76 19.32
Median PFS, mos 8.2 8.4
 12-mo rate, % 41.3 42.1 1.06 (0.86-1.30; P = .72)
 Patients with event, % 66.2 64.8

KEYNOTE-598: Safety
Treatment Related*† Immune Mediated*‡
AE, n (%) Pembro + Ipi Pembro + Pbo Pembro + Ipi Pembro + Pbo
(n = 282) (n = 281) (n = 282) (n = 281)
Any grade 215 (76.2) 192 (68.3) 126 (44.7) 91 (32.4)
Grade 3-5 99 (35.1) 55 (19.6) 57 (20.2) 22 (7.8)
Serious AEs 78 (27.7) 39 (13.9) 54 (19.1) 20 (7.1)
AEs leading to death 7 (2.5) 0 6 (2.1) 0
AEs leading to treatment discontinuation
 Ipilimumab or placebo only 17 (6.0) 9 (3.2) 5 (1.8) 3 (1.1)
 Both drugs 54 (19.1) 21 (7.5) 34 (12.1) 12 (4.3)
*Months on ipi or pbo: 5.6 vs 8.8; mos on pembro: 6.3 vs 9.7. †Treatment-related AEs of greater risk in the pembro + ipi arm included
rash (17.4% vs 10.7 %), pneumonitis (9.9 % vs 4.3%), increased ALT (8.2% vs 3.9%), and increased AST (7.8% vs 3.2%). ‡Immune-
mediated AEs of greater risk in the pembro + ipi arm included pneumonitis (12.8 % vs 5.3%) and colitis (6.4% vs 1.1%).
 Median no. of cycles with pembrolizumab + ipi vs pembrolizumab + pbo: 10 vs 15 mos
Nivolumab + Ipilimumab vs Nivolumab in Previously
Treated Metastatic EGFR-Mutant NSCLC
 Randomized, open-label, phase II study
Stratified by PD-L1 TPS Blood draw and CT scan 24 wks Blood draw and CT
(< 1% vs ≥ 1%) and brain every 6 wks scan every 12 wks
metastasis (yes vs no)
For 2 yrs
Nivolumab 3 mg/kg Q2W
Patients with advanced
Ipilimumab 1 mg/kg Q6W
EGFR-mutant NSCLC who failed
(n = 16) Trial terminated
1 prior EGFR TKI and ≤ 1 prior Crossover
chemotherapy; ECOG PS 0-2; allowed early due to
treated or stable brain Nivolumab 3 mg/kg Q2W if PD futility
metastases allowed (n = 15)
(N = 31)
Baseline tissue 12 wks Tissue biopsy Exome 12 wks PD: Tissue biopsy
biopsy sequencing RNA-seq and blood draw
 Primary endpoint: ORR  Secondary endpoints: PFS, OS, DoR, toxicity, salvage capability
of crossover to combination therapy, biomarker analyses
Lai. WCLC 2020. Abstr OA01.06. Slide credit: clinicaloptions.com

Nivolumab + Ipilimumab vs Nivolumab in
EGFR-Mutant NSCLC: Baseline Characteristics
Nivolumab + Ipilimumab Nivolumab Total Population
Characteristic (n = 16) (n = 15) (N = 31)
Median age, yrs (range) 59.1 (39.3-79.8) 70.7 (50.8-80.2) 62.6 (39.3-80.2)
Female, n (%) 8 (50.0) 4 (26.7) 12 (38.7)
Current/former smoker, n (%) 3 (18.8) 3 (20.0) 6 (19.3)
PD-L1 status, n (%)
 < 1% 8 (50.0) 6 (40.0) 14 (45.2)
 ≥ 1% 8 (50.0) 8 (53.3) 16 (51.6)
 Indeterminate 0 1 (6.7) 1 (3.2)
EGFR mutation, n (%)

 Exon 19 del 11 (68.8) 9 (60.0) 20 (64.5)
 L858R 5 (31.2) 5 (33.3) 10 (32.3)
 Other (A763_Y764insFQEA) -- 1 (6.7) 1 (3.2)
Presence of T790M, n (%) 9 (56.2) 5 (33.3) 14 (45.2)
Brain metastasis, n (%) 9 (56.2) 7 (46.7) 16 (51.6)

EGFR-Mutant NSCLC: Efficacy
Nivolumab + Total  5 patients attained clinical benefit
Efficacy Ipilimumab Nivolumab Population
Outcome
(n = 16)
(n = 15)
(N = 31) (PR or ongoing PR/SD at 6 mos)
Best overall ‒ All had EGFR exon 19 del
response, n (%)
 PR 1 (6.3) 0 1 (3.2) ‒ 4 of 5 were T790M negative
 SD 6 (37.5) 6 (40.0) 12 (38.7)
 PD 9 (56.3) 8 (53.3) 17 (54.8)  6 patients had shrinkage of biopsied
Median PFS, mos
1.22 (1.15-NE) 1.31 (1.22-NE) 1.31 (1.15-2.53) lesions
(95% CI)
6-mo PFS, % ‒ 5 developed intracranial disease/brain
8.9 (1.5-54.4) 8.3 (1.3-52.6) 9.0 (2.5-31.8) metastasis during treatment, leading to
(95% CI)
failure
 3 patients crossed over from nivolumab
alone to nivolumab + ipilimumab
‒ None achieved response after
crossover

EGFR-Mutant NSCLC: Biomarker Analyses
 PD-L1 status did not correlate with response to immune checkpoint inhibition
 TMB did not correlate with response to immune checkpoint inhibition
‒ Low TMB observed in 13 evaluable patients (median TMB: 3.34 mutations/Mb)
‒ No patient with clinical benefit had TMB ≥ 10 mutations/Mb
 GEP did not correlate with response to immune checkpoint inhibition
‒ Only 2 of 24 evaluable samples (8.3%) had high GEP at baseline
 GEP analysis of paired biopsy samples (n = 8) showed that patients with clinical
benefit had:
‒ Immunologically hot tumors at baseline and/or on treatment
‒ Lower numbers of suppressive MDSCs at baseline and on treatment

EGFR-Mutant NSCLC: Safety
Total Population (N = 31)  71% of total population received an EGFR
Treatment-Related
AEs, n (%) Any Grade Grade 3 TKI immediately before starting study
immunotherapy
Any 23 (74.2) 2 (6.0)
Immune related ‒ No major safety concerns with transition to
 Skin 11 (35.5) -- immune checkpoint inhibition
 Endocrine 4 (12.9) 1 (3.2)
 Gastrointestinal 3 (9.6) --  Similar incidence of any-grade treatment-
 Hepatic 3 (9.6) --
 Pulmonary 1 (3.2) -- related AEs with nivo + ipi vs nivo alone:
 Musculoskeletal -- 1 (3.2) 80% vs 75%
 2 grade 3 toxicities, both in nivo + ipi arm
‒ Type 1 diabetes mellitus
‒ Myositis
 1 pneumonitis event (grade 1) in nivo arm

EMPOWER-Lung 1: Exploratory Analysis of Outcomes by
PD-L1 Expression
 In phase III EMPOWER-Lung 1 trial, first-line cemiplimab monotherapy showed superior median OS and PFS, higher ORR and
longer DoR vs standard chemotherapy in advanced NSCLC patients with PD-L1 ≥ 50% [1]
‒ Exploratory analysis examined clinical outcomes by PD-L1 expression level in prespecified PD-L1 ≥ 50% cohort [2,3]
Until PD or 108 wks
Exploratory Analysis Cohort[2,3]
PD: May continue  Testing acording to
Patients with Cemiplimab 350 mg Q3W cemiplimab + 4 instructions for use at
treatment naive advanced Until PD or 108 wks cycles chemotherapy entry (n = 475)*
NSCLC, PD-L1 ≥ 50%, no
 Testing not according to
EGFR/ALK/ROS1 mutations,
PD: Crossover instructions; PD-L1 ≥ 50%
ECOG PS 0/1
Chemotherapy 4-6 cycles allowed to on retest (n = 88)
(N = 710)[1-3]
investigator’s choice cemiplimab
Total PD-L1 ≥ 50% cohort
Stratified by histology and monotherapy
n = 563†
geographical region
(Europe, Asia, ROW)
 Primary endpoints: OS and PFS[1-3]  Secondary endpoints: ORR, DoR, HRQoL, and safety[1-3]
*Enrolled after August 2018 and not subject to PD-L1 retesting because initial test performed according to the assay's instructions for use.
†
Prespecified cohort consisting of patients with testing according to instructions and patients with PD-L1 ≥ 50% on retest.
1. Sezer. ESMO 2020. Abstr LBA52. 2. Kilickap. WCLC 2020. Abstr OA01.03. 3. Sezer. Lancet. 2021;397:592. Slide credit: clinicaloptions.com
EMPOWER-Lung 1: Baseline Characteristics for
PD-L1 Analysis
PD-L1 Tested at Study Entry All PD-L1 50%
Characteristic Cemiplimab Chemotherapy Cemiplimab Chemotherapy
(n = 238) (n = 237) (n = 283) (n = 280)
Median age, yrs (range) 64 (31.0-79.0) 64 (40.0-84.0) 63 (31.0-79.0) 64 (40.0-84.0)
 ≥ 65 yrs of age, n (%) 108 (45.4) 118 (49.8) 126 (44.5) 133 (47.5)
Male, n (%) 207 (87.0) 194 (81.9) 248 (87.6) 231 (82.5)
Region: Europe/Asia/other, % 73.5/12.2/14.3 75.1/11.0/13.9 76.0/11.0/13.1 77.1/10.4/12.5
ECOG PS 0/1, % 27.3/72.7 25.7/74.3 27.2/72.8 26.8/73.2
Histology: squamous/nonsquamous, % 42.0/58.0 41.1/58.6 43.1/56.9 43.2/56.8
Brain metastases, % 11.8 13.9 12.0 12.1
Stage at screening: locally advanced/metastatic, % 13.4/86.6 13.9/86.1 15.9/84.1 15.0/85.0
PD-L1 expression tertile
 ≥ 90% 33.6 34.2 34.6 33.6
 > 60% to < 90% 31.9 30.4 31.4 32.1
 ≥ 50% to ≤ 60% 34.5 35.4 33.9 34.3
Kilickap. WCLC 2020. Abstr OA01.03. Slide credit: clinicaloptions.com

EMPOWER-Lung 1: Responses by PD-L1 Expression Level
 PD-L1 expression levels correlate with tumor responses
Objective Response Rate
39.5% 38.8%
45 35.3% (95% CI: (95% CI: Tumor Size Reduction
(95% CI: 28.4-51.4) 28.1-50.3) 0
40 29.2-41.7) 28.0%
(LOCF)
35 (95% CI:
-10
Median % Δ in
Tumor Size (LOCF)

30 18.7-39.1) 21.4% Chemotherapy PD-L1 ≥ 50%
Median % Δ in
17.7% (95% CI: 16.7%
Size %
25 14.8%
(95% CI: 13.2-31.7) (95% CI: -20 Chemotherapy PD-L1 ≥ 50% and ≤ 60%
TumorORR,
20 13.1-23.2) (95% CI:

8.9-27.3)
7.9-24.4)
15 -30 Cemiplimab PD-L1 ≥ 50%
10 Cemiplimab PD-L1 > 60% and < 90%
5 -40
0 Cemiplimab PD-L1 ≥ 90%
≥ 50% ≥ 50% to ≤ 60% ≥ 60% to < 90% ≥ 90% -50
Overall PD-L1 Expression Tertile 0 3 6 9 12 15 18 21 24 27 30
Cemiplimab PD-L1 ≥ 50% Chemotherapy PD-L1 ≥ 50% Mos
Cemiplimab PD-L1 ≥ 50% and ≤ 60% Chemotherapy PD-L1 ≥ 50% and ≤ 60%
Cemiplimab PD-L1 > 60% and < 90% Chemotherapy PD-L1 > 60% and < 90%
Cemiplimab PD-L1 ≥ 90% Chemotherapy PD-L1 ≥ 90%
Kilickap. WCLC 2020. Abstr OA01.03. Reproduced with permission. Slide credit: clinicaloptions.com
EMPOWER-Lung 1 in PD-L1 ≥ 50% NSCLC: Efficacy
 Cemiplimab monotherapy: superior median OS/PFS vs chemotherapy in PD-L1 ≥ 50% subpopulation
PD-L1 Tested at Study Entry Cemiplimab (N=475) Chemotherapy (N=475)
All PD-L1 ≥ 50% Cemiplimab (N=563) Chemotherapy (N=563)
Median, Mos (95% CI) HR (95% CI) Median, Mos (95% CI) HR (95% CI)
OS NR (NE-NE) vs 12.1 (10.2-17.5) 0.57 (0.40-0.80) PFS 6.3 (4.5-8.5) vs 5.6 (4.3-6.2) 0.60 (0.47-0.77)
NR (17.9-NE) vs 14.2 (11.2-17.5) 0.57 (0.42-0.77) 8.2 (6.1-8.8) vs 5.7 (4.5-6.2) 0.54 (0.43-0.68)
1.0 1.0
PFS Probability
0.8 0.8
OS Probability
12-Mo PFS, % (95% CI)

39.3 (31.6-47.0) vs 6.9 (3.0-12.9)
0.6 0.6 40.7 (33.7-47.5) vs 7.1 (3.6-12.1)
0.4 12-Mo OS, % (95% CI)

0.4
71.5 (63.7-77.9) vs 50.8 (41.8-59.1)
0.2 72.4 (65.6-78.1) vs 53.9 (46.2-61.1) 0.2
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32
Patients at Risk, n Mos Mos
Cemiplimab 238 200 165 141 120 76 53 26 14 0 0 0 0 0 0 0 0 238 181 130 93 67 38 24 10 4 0 0 0 0 0 0 0 0
Chemotherapy 237 200 163 123 98 62 36 20 8 0 0 0 0 0 0 0 0 237 183 128 84 33 15 5 1 1 0 0 0 0 0 0 0 0
Cemiplimab 283 244 203 177 154 103 83 55 42 24 18 15 10 6 3 1 0 283 221 162 123 92 59 43 28 20 14 11 9 5 3 0 0 0
Chemotherapy 280 239 198 153 125 87 57 41 25 15 11 6 4 2 1 0 0 280 220 157 104 42 20 8 4 3 0 0 0 0 0 0 0 0
EMPOWER-Lung 1: Survival by PD-L1 Expression Level
 PD-L1 expression levels correlate with survival outcomes and cemiplimab therapy
Cemiplimab PD-L1 ≥ 90%
OS Cemiplimab PD-L1 > 60% and < 90% PFS
1.0 Cemiplimab PD-L1 ≥ 50% and ≤ 60%
1.0
0.8 Chemotherapy PD-L1 ≥ 90% 0.8

Tumor Size (LOCF)
OS Probability
PFS Probability
Chemotherapy PD-L1 > 60% and < 90%
Median % Δ in
0.6 Chemotherapy PD-L1 ≥ 50% and ≤ 60% 0.6
0.4 0.4
0.2 0.2
0 0
0 2 4 6 8 10 12 14 16 18 0 2 4 6 8 10 12 14 16 18
Mos Mos
Median, Mos (95% CI) HR (95% CI) Mos
Median, Mos (95% CI) HR (95% CI)
Cemiplimab (N = 238) Chemotherapy (N = 237) Cemiplimab (N = 238) Chemotherapy (N = 237)
≥ 90% NR (13.4-NE) vs 13.3 (10.2-NE) 0.54 (0.27-1.10) ≥ 90% 12.7 (9.8-13.4) vs 6.1 (4.2-6.2) 0.33 (0.19-0.58)
> 60 to < 90% NR (NE-NE) vs 14.2 (9.6-17.5) 0.49 (0.26-0.92) > 60 to < 90% 6.2 (4.2-8.4) vs 4.3 (4.1-5.9) 0.57 (0.38-0.85)
≥ 50% and ≤ 60% NR (13.2-NE) vs 11.7 (8.3-NE) 0.74 (0.44-1.24) ≥ 50% and ≤ 60% 4.3 (2.8-5.2) vs 6.0 (4.4-6.2) 0.89 (0.61-1.29)
EMPOWER-Lung1 PD-L1 Analysis:
Safety in All Treated Patients
Cemiplimab Chemotherapy Cemiplimab Chemotherapy
AE, % AE, %
(n = 355) (n = 342) (n = 355) (n = 342)
Grade Any ≥3 Any ≥3 Grade Any ≥3 Any ≥3
Treatment-emergent 88.2 37.2 94.2 48.5 Treatment-emergent 88.2 37.2 94.2 48.5
 Led to d/c 6.5 4.2 4.1 2.3
Anemia 14.6 3.4 50.0 16.4  Led to death 9.6 9.6 9.1 9.1
Decreased appetite 11.8 0.6 18.4 0.3
Treatment-related 57.5 14.1 88.6 39.2
Fatigue 10.1 1.1 17.0 1.5  Led to d/c 5.1 2.5 3.5 2.3
 Led to death 2.5 2.5 2.0 2.0
Pneumonia 9.3 4.8 10.8 5.6
Constipation 7.6 0 15.2 0 Immune-related 17.5 3.7 2.3 0.3
 Led to d/c 2.5 1.4 0 0
Nausea 6.2 0 28.4 1.2  Led to death 0.3 0.3 0 0
Vomiting 4.2 0 14.3 1.2
Thrombocytopenia 2.0 0 15.2 8.2
Neutropenia 1.7 0.6 18.4 10.2
Decreased platelets 1.4 0 10.5 3.5  Median duration of exposure: 27.3 wks in
Alopecia 1.1 0 24.0 0.6 cemiplimab arm and 17.7 wks in chemotherapy
Peripheral neuropathy 0.8 0.3 10.8 0.3 arm
Decreased neutrophils 0.6 0.3 12.3 5.3
Kilickap. WCLC 2020. Abstr OA01.03. Slide credit: clinicaloptions.com
POPLAR/OAK: Comutations in DDR Pathways and
Response to Atezolizumab in NSCLC
 Exploratory analysis[1] assessed predictive value of comutations in DDR pathways for
response to atezolizumab among previously treated NSCLC patients in the phase II
POPLAR[2] and phase III OAK[3] trials
 Genetic alterations, blood tumor mutational burden assessed with Foundation One NGS
assay
‒ Analyzed 29 genes in 7 DDR pathways
‒ Deleterious mutations determined based on nonsense mutations, splice site alterations, manual
review of missense mutations
 Comutation-positive status defined as deleterious alterations in ≥ 2 DDR pathways or
deleterious alteration in 1 DDR pathway AND missense mutations in other DDR pathways
‒ 853 treated trial participants had evaluable NGS data; 49 identified with comutations
(30 treated with atezolizumab, 19 treated with docetaxel)
1. Nie. WCLC 2020. Abstr OA07.03. 2. Fehrenbacher. Lancet. 2016; 387:1837. 3. Rittmeyer. Lancet. 2016;389:255. Slide credit: clinicaloptions.com
POPLAR/OAK Analysis of DDR Comutations and
Atezolizumab Response: Baseline Characteristics
Comutation Comutation Comutation Comutation
Characteristic Positive Negative Characteristic Positive Negative
(n = 49) (n = 804) (n = 49) (n = 804)
Median age, yrs (range) 62 (57-68) 63 (57-70) PD-L1
 TC0-2 or IC0-2 81.8 82.8
Female, % 32.7 38.6  TC3 or IC3 18.2 17.2
ECOG PS, %
0 Treatment, %
28.6 33.6
1 71.4 66.4  Atezolizumab 61.2 49.6
 Docetaxel 38.8 50.4
Smoking history, %
 Never Median SLD, mm (IQR)* 92 (57-144) 72 (45-105)
75.5 84.3
 Former or current 24.5 15.7 Median metastatic sites, n (IQR)† 3 (2.5-4) 3 (2-4)
Histology, % Median blood TMB (mut/Mb)‡ 20 7
 Nonsquamous 69.4 70.1 (13.5-29.5) (3-15)
 Squamous 30.6 29.9
*Difference in comutation status: P = .006. †Difference in comutation
status: P = .026. ‡Difference in comutation status P < .001.
Nie. WCLC 2020. Abstr OA07.03. Slide credit: clinicaloptions.com

POPLAR/OAK Analysis of DDR Comutations and
Atezolizumab Response: Response and Survival
Atezolizumab Docetaxel
Outcome, % Comutation Comutation Comutation Comutation
n Positive n Negative n Positive n Negative
Durable clinical benefit (PFS ≥ 6 mos) 30 56.7 399 30.6 19 21.1 405 28.1
ORR 30 26.7 365 14.8 17 11.8 352 15.6
Comutation Positive Comutation Negative
Interaction
Survival Atezolizumab Docetaxel Atezolizumab Docetaxel P Value
(n = 30) (n = 19) (n = 399) (n = 405)
Median PFS, mos (95% CI) 6.9 (1.0-12.8) 3.3 (2.6-3.9) 2.7 (2.2-3.1) 3.6 (3.0-4.2)
.010
HR (95% CI) 0.40 (0.21-0.75) 0.95 (0.82-1.11)
12-mo PFS, % 28.9 5.3 17.2 10.2
Median OS, mos (95% CI) 14.9 (9.7-20.0) 6.2 (3.6-8.9) 12.5 (10.1-15.0) 9.1 (8.3-10.0)
.014
HR (95% CI) 0.30 (0.15-0.58) 0.70 (0.59-0.83)
12-mo OS, % 63.3 21.1 50.8 36.3
Nie. WCLC 2020. Abstr OA07.03. Slide credit: clinicaloptions.com

Key Immunotherapy Studies in NSCLC: Summary
 KRAS and TP53 mutations and response to ICI: TP53/KRAS comutations associated with better PFS
with ICI vs CT and was independent of TMB, PD-L1 expression, clinicopathology status, or
immunotherapy-related mutations[1]
 KEYNOTE-598: adding ipi to pembrolizumab did not improve efficacy as first-line therapy and was
associated with higher toxicity; pembro remains the SoC in patients with TPS ≥ 50%[2]
 Nivo ± ipi in EGFR-mutant NSCLC: ICI did not confer clinical benefit in patients with EGFR TKI-
resistant NSCLC; PD-L1, TMB, and GEP did not predict response to ICI, and ICI post EGFR TKI did not
lead to undue toxicity or major safety concerns[3]
 EMPOWER-Lung 1: in the exploratory analysis, benefit with cemiplimab was incrementally
associated with increasing PD-L1 expression levels, including for PFS and OS, and a larger reduction
in tumor volume[4]
 DDR comutations and atezolizumab response: atezolizumab monotherapy was associated with
better response, PFS, and OS, in patients with comutation status; additional studies warranted[5]
1. Li. WCLC 2020. Abstr OA07.06. 2. Boyer. WCLC 2020. Abstr PS01.09. 3. Lai. WCLC 2020. Abstr OA01.06.
4. Kilickap. WCLC 2020. Abstr OA01.03. 5. Nie. WCLC 2020. Abstr OA07.03. Slide credit: clinicaloptions.com
Early-Stage NSCLC
ADAURA: Adjuvant Osimertinib vs Placebo in
Resected EGFR-Mutated NSCLC
 Global, randomized, double-blind phase III trial (data cutoff: 1/17/2020)[1]
‒ IDMC recommended early unblinding due to efficacy; at time of unblinding, trial had completed enrollment
and all patients had ≥ 1 yr of follow-up  Primary endpoint: investigator-
Stratified by stage (IB vs II vs IIIA), assessed DFS in patients with
Patients with completely EGFR mutation (ex19del vs L858R), stage II/ IIIA disease
resected stage IB/II/IIIA primary race (Asian vs non-Asian)
nonsquamous NSCLC with ‒ Primary endpoint met
negative margins; with lower rate of disease
primary nonsquamous NSCLC Osimertinib 80 mg QD
(n = 339) Until 3 yrs, recurrences for adj
with EGFR ex19del or L858R*; osimertinib vs placebo
recurrence, or
aged ≥ 18 yrs (≥ 20 yrs in (HR: 0.17)[1]
d/c criterion
Japan/Taiwan); WHO PS 0/1;
Placebo QD met†
brain imaging done;  Exploratory endpoints: HRQoL,
(n = 343)
adj CT permitted;
maximum time from surgery to
DFS outcomes with or without
randomization: 10 wks without *Confirmed centrally using tissue. †Follow-up: until recurrence, postoperative chemotherapy
adj CT, 26 wks with adj CT Wks 12 and 24, then Q24W to 5 yrs, then yearly; after outcomes after adj
(N = 682)[1-4] recurrence, Q24W for 5 yrs, then yearly. osimertinib[2,4]
1. Wu. NEJM. 2020;383:1711. 2. Wu. WCLC 2020. Abstr OA06.04. 3. NCT04351555. 4. Majem. WCLC 2020. Abstr OA06.03. Slide credit: clinicaloptions.com
ADAURA: Baseline Characteristics
Characteristic, % Osimertinib (n = 339) Placebo (n = 343)
Men/women, % 32/68 28/72
Smoker/nonsmoker,* % 32/68 25/75
Asian/non-Asian, % 64/36 64/36
WHO PS 0/1, % 64/36 64/36
Brain imaging: MRI/CT/neither, % 54/45/< 1 48/52/0
AJCC stage at diagnosis (7th edition): IB/II/IIIA, % 32/34/35 32/34/34
Adenocarcinoma/other histology,† % 96/4 97/3
EGFR ex19del/L858R,‡ % 55/45 55/45
Prior adjuvant chemotherapy, % 60 60
*Former smoker: osimertinib, n = 104; placebo, n = 83. Current smoker: osimertinib, n = 4; placebo, n = 3. Never smoker: osimertinib, n = 231;
placebo, n = 257. †Includes bronchial gland carcinoma (NOS): osimertinib, n = 1; placebo, n = 2; malignant adenosquamous carcinoma: osimertinib,
n = 4; placebo, n = 5; other: osimertinib, n = 8; placebo, n = 4. ‡Centrally assessed at randomization.
Wu. WCLC 2020. Abstr OA06.04. Slide credit: clinicaloptions.com

ADAURA: Receipt of Adjuvant Chemotherapy
 410/682 (60%) patients in the Characteristic, % n Received Adjuvant CT
trial received adjuvant CT AJCC stage at diagnosis (7th
edition)*
 IB 216 26
‒ Median duration: 4 cycles  II 231 71
 IIIA 235 80
 All but 1 patient (409/410) Age
received platinum-based CT  < 70 yrs 509 66
 ≥ 70 yrs 173 42
 Adjuvant CT use more common in: WHO PS
0 434 60
‒ Stage II/IIIA vs IB disease 1 248 60
Enrollment region
‒ Patients aged < 70 vs ≥ 70 yrs  Asia† 414 65
 Outside of Asia‡ 268 53
‒ Patients enrolled in Asia *Includes only patients who received platinum-based chemotherapy (n = 409).
†
Japan: n = 71; China: n = 106; Asia non-Japan, non-China: n = 91. ‡Enrolled in
Europe, Australia, United States, Canada, or Brazil.
ADAURA: DFS With/Without Adjuvant Chemotherapy,
by Disease Stage
Median DFS, Mos (95% CI) Osimertinib Placebo HR (95% CI)
Overall population
 With adjuvant CT NR (38.8-NC) [n = 203] 22.1 (17.4-32.9) [n = 207] 0.16 (0.10-0.26)
 Without adjuvant CT NR (NC-NC) [n = 136] 33.1 (22.6-NC) [n = 136] 0.23 (0.13-0.40)
Stage IB
 With adjuvant CT NR (33.0-NC) [n = 28] 48.2 (21.0-48.2) [n = 30] NC (NC-NC)
 Without adjuvant CT NR (NC-NC) [n = 78] NR (NC-NC) [n = 76] 0.38 (0.15-0.88)
Stage II
 With adjuvant CT NR (NC-NC) [n = 81] 29.4 (22.1-NC) [n = 85] 0.15 (0.06-0.32)
 Without adjuvant CT NR (27.7-NC) [n = 37] 22.1 (10.8-NC) [n = 33] 0.20 (0.07-0.52)
Stage IIIA
 With adjuvant CT 38.8 (34.3-NC) [n = 94] 12.9 (10.9-19.4) (n = 92) 0.13 (0.06-0.23)
 Without adjuvant CT 38.6 (38.6-NC) [n = 21] 11.2 (8.2-21.9) (n = 27) 0.10 (0.02-0.29)
 Rates of DFS events in osimertinib arm with and without adjuvant CT comparable in overall population
(11% vs 11%)

ADAURA HRQoL: SF-36 Compliance and Baseline Scores
 HRQoL measured with SF-36 at BL, Wk 12, Wk 24, and Q24W until treatment ended
‒ Features 2 summary scores, PCS and MCS, each consisting of 4 health domains
 ≥ 85% of eligible patients in osimertinib and placebo arms completed SF-36 at all time
points throughout the study
‒ Only 12% and 10% of patients in osimertinib and placebo arms, respectively, had completed
study treatment (3 yrs) at data cutoff
 BL PCS and MCS T-scores comparable between arms (range: 46-47) and only slightly lower
than general population mean (0.3-0.4 SD below normative mean)
 BL health domain T-scores comparable between arms; most were comparable with general
population mean (± 0.3 SD of normative mean), except for Role-Physical, Social
Functioning, and Role-Emotional (0.4-0.9 SD below normative mean)
Majem. WCLC 2020. Abstr OA06.03. Slide credit: clinicaloptions.com

ADAURA HRQoL: Adjusted Mean Change in
SF-36 T-Scores
 SF-36 component scores maintained over time in osimertinib arm, with no clinically
meaningful differences compared with placebo
MMRM Adjusted Mean Change From BL (95% CI)
Clinically Meaningful
SF-36 Component
Osimertinib Placebo Osimertinib vs Placebo Change*
Summary score
 PCS 1.13 (0.54 to 1.72) 2.31 (1.70 to 2.91) -1.18 (-2.02 to -0.34) ±2
 MCS 1.34 (0.60 to 2.08) 2.68 (1.92 to 3.44) -1.34 (-2.40 to -0.28) ±3
Health domain
 Physical functioning
 Role-physical 0.53 (-0.10 to 1.16) 1.38 (0.74 to 2.03) -0.86 (-1.76 to 0.04) ±3
 Bodily pain 2.67 (1.91 to 3.43) 4.47 (3.69 to 5.25) -1.80 (-2.90 to -0.71) ±3
 General health 1.66 (0.91 to 2.40) 2.22 (1.45 to 2.99) -0.57 (-1.64 to 0.50) ±3
 Vitality -0.41 (-1.12 to 0.31) 1.09 (0.36 to 1.83) -1.50 (-2.53 to -0.47) ±2
 Social functioning 0.98 (0.22 to 1.74) 2.91 (2.13 to 3.69) -1.93 (-3.02 to -0.84) ±2
 Role-emotional 2.77 (2.06 to 3.49) 3.88 (3.14 to 4.62) -1.11 (-2.13 to -0.08) ±3
 Mental health 1.05 (0.22 to 1.87) 2.51 (1.66 to 3.36) -1.46 (-2.65 to -0.28) ±4
1.17 (0.44 to 1.90) 2.05 (1.30 to 2.80) -0.88 (-1.92 to 0.17) ±3
*As defined by 3rd edition SF-36 scoring manual.
ADAURA: Deterioration of SF-36 Components
 > 80% of patients in both arms Time to Deterioration for
HR (95% CI)
did not experience clinically Osimertinib vs Placebo
meaningful deterioration in Summary score

 PCS 1.17 (0.82-1.67)
PCS or MCS  MCS 0.98 (0.70-1.39)
 Among patients who did Health domain*

 Bodily pain
experience deterioration,  General health 0.92
 Mental health 1.15
no differences in time to  Physical functioning 1.14
deterioration observed between  Role-emotional 1.18
 Role-physical 1.02
osimertinib and placebo  Social functioning 1.19
 Vitality 0.68
1.18
*95% CI values not provided, but all intervals crossed 1.

ITACA: Tailored vs Standard Adjuvant Chemotherapy in
Completely Resected Stage II-IIIA NSCLC
 Randomized, multi-national, open-label,
active-controlled phase III trial Paclitaxel (n = 137)
Profile 1
High
Cisplatin doublet, investigator choice (n = 127)
TS mRNA
High*‡ expression
Profile 2
Adults with completely Pemetrexed (n = 35)
resected (R0) stage II-IIIA Low
NSCLC, ECOG PS 0/1, ECCR1 Stratification by Cisplatin doublet, investigator choice (n = 41)
mRNA disease stage and
interval of 45-60 days
smoking status
between surgery and start expression
Profile 3
Cisplatin/Gemcitabine (n = 85)
of chemotherapy High
(N = 690) TS mRNA Cisplatin doublet, investigator choice (n = 98)
Low†‡
expression
Cisplatin/Pemetrexed (n = 87)
Profile 4
*Cisplatin not allowed in tailored arms. †Cisplatin allowed in tailored arms. Low
‡
High ECCR1 or TS mRNA expression defined as ≥ median value as assessed in Cisplatin doublet, investigator choice (n = 80)
previous pilot study; with cutoff for ERCC1 = 1.42, and TS = 0.50.
 Primary endpoint: OS  Secondary endpoints: RFS, toxicity, treatment compliance and

correlation of ERC1 and TS mRNA with protein
Novello. WCLC 2020. Abstr PS01.04. Slide credit: clinicaloptions.com
ITACA: Baseline Characteristics
Characteristic Tailored Therapy (n = 344) Standard Therapy (n = 346)
Median age, yrs 65 64
Male, % 70 68
Current/former/never smoker, % 54/34/12 48/41/11
ECOG PS 0/1, % 76/24 78/22
Stage II/IIIA, % 60/40 58/42
Histology, %
 Adenocarcinoma 59 59
 Squamous cell carcinoma 35 34
 Large cell carcinoma 3 5
 Other 3 2
Type of surgery, %
 Lobectomy* 83 76
 Pneumonectomy 17 14
*Including also bilobectomy and sleeve lobectomy.

ITACA: Treatment Received
Profile 1 Profile 2 Profile 3 Profile 4
Overall
(ECCR1 High, TS High) (ECCR1 High, TS low) (ECCR1 Low, TS High) (ECCR1 Low, TS Low)
Treatment, %
Tailored Standard Tailored Standard Tailored Standard Tailored Standard Tailored Standard
(n = 137) (n = 127) (n = 35) (n = 41) (n = 85) (n = 98) (n = 87) (n = 80) (n = 344) (n = 346)
Cisplatin +
 Vino 0 35 0 32 0 39 0 34 0 36
 Gem 0 46 0 34 98 49 0 49 24 46
 Doce 0 7 0 15 0 5 0 4 0 7
 Pem 0 0 3 0 0 1 100 5 26 2
 NS 0 6 0 17 0 6 0 8 0 8
Pac alone 98 5 3 0 0 0 0 0 39 0
Pem alone 1 0 94 2 1 0 0 0 10 0
None 0 0 0 0 1 0 0 0 1 0
Other 1 1 0 0 0 0 0 0 0 0
 Patients in the tailored- and standard-therapy arms received a median of 4 cycles (range: 1-4) of tx

ITACA: RFS and OS (ITT Analysis)
RFS OS
1.00 1.00
HR: 0.94 (95% CI: 0.74-1.20) HR: 0.76 (95% CI: 0.55-1.04)
RFS Probability
OS Probability
0.75 0.75
0.50 0.50
0.25 Median RFS, Mos 0.25 Median OS, Mos

Tailored therapy 64.4 Tailored therapy 96.4
Standard therapy 41.5 Standard therapy 83.5
0 0
Patients at
0 12 24 36 48 60 72 84 96 Patients at
0 12 24 36 48 60 72 84 96
Risk, n Mos Risk, n Mos
Tailored 334 208 126 92 70 44 31 18 8 Tailored 344 239 156 108 78 49 35 20 8
Standard 346 201 128 93 67 40 29 14 8 Standard 346 221 155 110 74 48 33 17 8
 Median follow-up: 28.2 mos (IQR: 9.9-55.8)  Study underpowered on final OS analysis based on
only 46% of expected events
Novello. WCLC 2020. Abstr PS01.04. Reproduced with permission. Slide credit: clinicaloptions.com
ITACA: Adverse Events (PP Analysis)
Grade 3/4 AE, n (%) Tailored Therapy Standard Therapy Grade 3/4 AE, n (%) Tailored Therapy Standard Therapy
Any 110 (32.6) 155 (45.9) Decreased appetite 2 (0.6) 1 (0.3)

Neutropenia 45 (13.4) 64 (18.9) Dyspnea 2 (0.6) 1 (0.3)
Leukopenia 13 (3.9) 45 (13.3) Mucositis 2 (0.6) 0
Thrombocytopenia 11 (3.3) 26 (7.7) Asthenia 1 (0.3) 5 (1.5)
Nausea 13 (3.9) 15 (4.4) Stomatitis 1 (0.3) 0
Fatigue 9 (2.7) 5 (1.5) Constipation 1 (0.3) 0
Vomiting 7 (2.1) 6 (1.8) Tinnitus/vertigo 0 1 (0.3)
Alopecia 7 (2.1) 0
Diarrhea 5 (1.5) 1 (0.3)  Grade 3/4 toxicity significantly less likely
Anemia 3 (0.9) 9 (2.7)
to occur with tailored vs standard tx
Myalgia 3 (0.9) 2 (0.6) ‒ OR: 0.57 (95% CI: 0.42-0.78; P < .001)
Hyperglycemia 3 (0.9) 1 (0.3)

Midtreatment PET/CT-Guided Adaptive RT in Locally
Advanced NSCLC (RTOG 1106)
 Multicenter, randomized phase II trial
Stratified by GTV
(200 cc) MLD (14 Gy)
Concurrent CRT to FDG PET/CT Adaptive CRT to MLD

Patients with inoperable
ED2 = 50 Gy in 17-21 20 Gy in 2.4-3.5 Gy/fx for 10 fxs
or unresectable
fractions* to a total of 66-100 Gy ED2/30 fxs
stage III NSCLC; FDG PET/CT-based RT plan
medically fit for 2:1
to 74 Gy ED2
concurrent CRT
Concurrent CRT 50 Continue Concurrent CRT to a
(N = 132)
Gy in 25 fractions total of 60 Gy ED2/30 fxs or
(ED2 = 50 Gy)* MLD of 20 Gy
*FDG PET/CT at 40-50 Gy ED2
for all patients.
 Primary endpoint: 2-yr local-regional  Key secondary endpoints: reduction in tumor

control rate per central review volume, adaptive RT dose escalation and RT plan
compliances, local regional PFS, OS, toxicity
Kong. WCLC 2020. Abstr OA02.04. NCT01507428. Slide credit: clinicaloptions.com

Phase II of PET/CT Adaptive RT: Efficacy Summary
 Minimum follow-up: 3.6 yrs
‒ 7 of 84 patients in adaptive RT arm did not receive protocol RT (no RT, n = 5; no adaptive RT, n = 2)
‒ Numerically higher local-regional/in-field local control with adaptive RT vs RT
Outcome Adaptive RT (n = 84) Standard RT (n = 43) P Value
Local-regional control by central review
 Fail events, n 31 15 --
 Median LRPF, mos (95% CI) 28.4 (19.1-NR) 27.5 (14.3-NR) .6585
 2-yr LRF rate, % 54.6 59.5 --
Local-regional control by site
In-field local tumor control by site
PFS  Fail events, n 67 31

 Median PFS, mos (95% CI) 13.2 (10.0-16.5) 12.2 (7.8-21.8) .5896
OS  Fail events, n 51 26
 Median OS, mos (95% CI) 31.2 (21.5-46.8) 35.5 (21.8-49.0) .7950
Kong. WCLC 2020. Abstr OA02.04. Slide credit: clinicaloptions.com

Phase II of PET/CT Adaptive RT: Safety Summary
Adaptive RT (n = 80) Standard RT (n = 42)
AE, n (%)
Grade 1/2 Grade 3/4 Grade 5 Grade 1/2 Grade 3/4 Grade 5
Overall highest grade 18 (22.5) 57 (71.3) 5 (6.3) 9 (21.4) 27 (64.3) 2 (4.8)
Blood and lymphatic system disorders 42 (52.6) 9 (11.3) 0 16 (38.1) 4 (9.5) 0
Anemia 41 (51.3) 8 (10.1) 0 18 (42.9) 2 (4.8) 0
Disseminated intravascular coagulation 0 0 0 0 1 (2.4) 0
Febrile neutropenia 0 1 (1.3) 0 0 1 (2.4) 0
Thoracic AE, n (%) Adaptive RT (n = 80) Standard RT (n = 42)

Any grade ≥ 2 AE 78 (97.5) 37 (88.1)
Grade ≥ 2 esophagitis 34 (42.5) 13 (31.0)
Grade ≥ 2 respiratory, thoracic, and
35 (43.8) 19 (45.2)
mediastinal disorders
Grade ≥ 2 cardiac disorders 4 (5.0) 2 (4.8)
Kong. WCLC 2020. Abstr OA02.04. Slide credit: clinicaloptions.com

Advances in the Treatment of Early-Stage NSCLC:
Summary
 ADAURA: like previously reported in primary analysis, patients treated with chemotherapy
after adjuvant osimertinib had improved DFS[1] and HRQoL[2]
‒ DFS benefit with osimertinib vs placebo observed regardless of whether patients did or did not
receive adjuvant CT across all disease stages
‒ HRQoL maintained during adjuvant osimertinib despite prolonged treatment, with no clinically
meaningful differences vs placebo
 ITACA: there was no statistically significant trend for benefit in OS or RFS for adjuvant
tailored CT vs standard CT using ECCR1 of TS mRNA expression[3]
‒ Customized treatment improved toxicity without compromising antitumor activity
 RTOG 1106: midtreatment PET/CT-guided adaptive RT did not meaningfully affect local-
regional control, PFS, or OS, but increased infield local-regional control by 11% and infield
primary tumor control by 17%[4]
1. Wu. WCLC 2020. Abstr OA06.04. 2. Majem. WCLC 2020. Abstr OA06.03. 3. Novello. WCLC 2020. Abstr PS01.04.
4. Kong. WCLC 2020. Abstr OA02.04. Slide credit: clinicaloptions.com
Small-Cell Lung Cancer
RESILIENT Part 1: Liposomal Irinotecan in SCLC After
First-line Platinum
 Randomized, open-label, single-arm, dose-exploration/expansion phase II
study
Dose Exploration* Dose Exploration/
Patients aged ≥ 18 yrs with
Expansion†
limited- or extensive-stage
SCLC who progressed Liposomal Irinotecan Liposomal Irinotecan
85 mg/m2 IV‡ Q2W 70 mg/m2 IV‡ Q2W Until PD or
on/after platinum-based unacceptable
6-wk cycles 6-wk cycles
first-line chemotherapy; toxicity
(n = 5) (n = 25)
ECOG PS 0/1; adequate organ
*4 patients experienced DLTs, and enrollment into dose expansion was initiated. †2 patients
function; prior developed DLTs and enrollment into dose expansion cohort was completed. ‡Patients received
immunotherapy allowed IV infusion over 90 minutes.
 Primary endpoints: safety/tolerability, recommended dose for part 2

 Key secondary endpoints: ORR, PFS, OS
Paz-Ares. WCLC 2020. Abstr FP10.04. NCT03088813. Slide credit: clinicaloptions.com
RESILIENT Part 1: Baseline Characteristics
Liposomal Irinotecan Liposomal Irinotecan All Patients
Characteristics
85 mg/m2 (n = 5) 70 mg/m2 (n = 25) (N = 30)
Median age, yrs (range) 62.0 (59-72) 59.0 (48-73) 61.5 (48-73)
Male, n (%) 3 (60.0) 9 (36.0) 12 (40.0)
White race, n (%) 5 (100) 25 (100) 30 (100)
Disease status, n (%)
 Locally advanced 0 2 (8.0) 2 (6.7)
 Metastatic 5 (100) 23 (92.0) 28 (93.3)
ECOG PS, %
 0* 1 (20.0) 3 (12.0) 4 (13.3)
 1† 4 (80.0) 22 (88.0) 26 (86.7)
Best response to prior therapies, n (%)
 CR 0 1 (4.0) 1 (3.3)
 PR 2 (40.0) 16 (64.0) 18 (60.0)
 SD 1 (20.0) 2 (8.0) 3 (10.0)
 PD 2 (40.0) 3 (12.0) 5 (16.7)
 Unknown 0 3 (12.0) 3 (10.0)
*Defined as patients who fully active. †Defined as patients with restricted activity.
Paz-Ares. WCLC 2020. Abstr FP10.04. Slide credit: clinicaloptions.com

RESILIENT Part 1: Efficacy
Liposomal Irinotecan Liposomal Irinotecan All Patients
Outcome 85 mg/m2 (n = 5) 70 mg/m2 (n = 25) (N = 30)
Best overall response, n (%)

 CR 0 1 (4.0) 1 (3.3)
 PR 2 (40.0) 10 (40.0) 12 (40.0)
 SD 1 (20.0) 7 (28.0) 8 (26.7)
 PD 1 (20.0) 5 (20.0) 6 (20.0)
 Not evaluable 1 (20.0) 2 (8.0) 3 (10.0)
ORR, % (95% CI) 40.0 (5.27-85.34) 44.0 (24.40-65.07) 43.3 (25.46-62.57)

Median DoR, mos (95% CI) 8.80 (4.11-NE) 2.99 (2.37-7.03) 3.78 (2.43-7.03)
Median PFS, mos (95% CI) -- 3.98 (1.45-4.24) --
Median OS, mos (95% CI) -- 8.08 (5.16-9.82) --

RESILIENT Part 1: Safety
Liposomal Irinotecan Liposomal Irinotecan
Characteristics All Patients (N = 30)
85 mg/m2 (n = 5) 70 mg/m2 (n = 25)
Duration of treatment, wks, mean (SD) 12.3 (9.19) 17.7 (14.94) 16.8 (14.17)
Total dose received, mg, median (range) 687.0 (160.0-1109.4) 714.0 (148.0-2295.8) 696.0 (148.0-2295.8)
Any TEAE, n (%) 5 (100) 25 (100) 30 (100)

 Leading to discontinuation/dose reduction 1 (20.0)/4 (80.0) 2 (8.0)/7 (28.0) 3 (10.0)/11 (36.7)
Any treatment-related TEAE, n (%) 5 (100) 24 (96.0) 29 (96.7)

Any treatment-related serious TEAE, n (%) 2 (40.0) 3 (12.0)* 5 (16.7)
Grade ≥ 3 TRAE or TEAE, n (%)

5 (100) 10 (40.0) 15 (50.0)
 Any 3 (60.0) 5 (20.0) 8 (26.7)
 Diarrhea 1 (20.0) 4 (16.0) 5 (16.7)
 Neutropenia 0 2 (8.0)* 2 (6.7)
 Abdominal sepsis 0 2 (8.0) 2 (6.7)
 Anemia 0 2 (8.0) 2 (6.7)
 Asthenia 0 2 (8.0) 2 (6.7)
 Thrombocytopenia 1 (20.0) 1 (4.0) 2 (6.7)
 Fatigue 1 (20.0) 1 (4.0) 2 (6.7)
 Hypokalemia 1 (20.0) 1 (4.0) 2 (6.7)
 Hypomagnesemia
*Abdominal sepsis related to treatment led to death in 2 patients.

Efficacy and Safety of Lurbinectedin + Irinotecan in
Relapsed SCLC
 Open-label, multicohort* phase Ib/II study
‒ Current analysis includes 21 SCLC patients from the phase II expansion in solid tumors
Phase Ib Dose Escalation: Cohort A Phase II Expansion

Patients with
advanced SCLC; 1 Lurbinectedin Day 1 + Lurbinectedin 2 mg/m2 Day 1 +
RD
or 2 prior lines of Irinotecan 75 mg/m2 Days 1, 8 IV Q3W Irinotecan 75 mg/m2 Days 1, 8 +
chemotherapy; (n = 39) G-CSF (n = 21)
ECOG PS 0/1
(N = 150) *Other phase Ib cohorts: cohort B ( n = 23) and cohort C (n = 3) dose-escalation ongoing.
 Primary endpoints: MTD, RD

 Key secondary endpoints: safety, PK, efficacy
Ponce-Aix. WCLC 2020. Abstr OA11.04. NCT02611024. Slide credit: clinicaloptions.com
Lurbinectedin + Irinotecan in Relapsed SCLC:
Characteristic Patients (n = 21) Characteristic Patients (n = 21)
Median age, yrs (range) 61 (52-74) Median sum longest diameters, mm 86 (19-180)
(range)
Men/women, % 48/52 CNS metastases, % 24
ECOG PS, % PCI, % 48
0 24
1 76 Median previous lines of treatment, n
(range) 1 (1-2)
LDH > ULN. % 76 62
 1 line, %
38
Limited/extensive stage, % 19/81  2 lines, %
CR/PR 71
Ex-lung sites, % Best response to 
90  SD 5
 Lymph nodes previous platinum, 19
 Liver 48  PD
38 % 5
 Adrenal  Unknown
 Bone 38
Median CTFI, mos 3.2
Bulky disease  < 90 days 38
29 62
(1 lesion > 50 mm), %  > 90 days
Ponce-Aix. WCLC 2020. Abstr OA11.04. Slide credit: clinicaloptions.com

Lurbinectedin + Irinotecan in Relapsed SCLC: Efficacy
CTFI Treatment Setting
All Patients
Outcome ≥ 90 Days < 90 Days Second Line Third Line
(n = 21)
(n = 13) (n = 8) (n = 13) (n = 8)
Median number of cycles, n (range) 8+ (1-20) 10+ (6-20) 6+ (1-8) 8+ (3-21) 8+ (1-18)
ORR (PR), % 62 69 50 77 38
CBR (PR + SD > 4 mos), % 81 92.3 62.5 92.3 62.5
DCR (PR + SD), % 90 100 75 100 75
6.7+ 7.5+ 3.7+ 6.7+ 3.0+
Median DoR, mos (95% CI)
(3.0-NR) (3.0-NR) (2.8-3.7) (3.0-NR) (3.0-NR)
Median PFS, mos (95% CI) 6.2+ 8.1+ 4.8+ 8.5+ 4.2+
(4.3-8.5) (4.3-NR) (0.7-5.0) (4.8-NR) (0.7-7.2)

Lurbinectedin + Irinotecan in Relapsed SCLC: Safety
Patients (n = 21) Outcome, n (%) Patients (n = 21)
TRAE and Laboratory
Abnormalities, %00 Grade 1/2 Grade 3/4 Any AE 21 (100)
AE Grade ≥ 3 AE 16 (76.2)
 Fatigue 66.7 23.8*
 Nausea 57.1 -- Serious AE 6 (28.5)
 Vomiting 38.1 4.8
 Diarrhea 33.3 28.6† Related AEs leading to
 Constipation 19 -- 0
death
 Abdominal pain 4.8 --
 Anorexia 52.4 -- Related AEs leading to
 Febrile neutropenia -- 9.5 0
treatment d/c
Laboratory abnormalities 6 (28.6)
Dose delay
 Anemia 81 19
(treatment related)
 Neutropenia 33.3 61.9‡
 Thrombocytopenia 66.7 9.5
Dose reduction 11 (52.4)
 ALT elevation 57.1 4.8
 AST elevation 61.9 4.8
RBC transfusion 7 (33.3)
*1 event per patient (n = 5). †All grade 3; 1 event per patient, except 1 patient with
CAFE 2 events of 1 day duration each. ‡6 of 21 patients with grade 4 neutropenia.
AMG 757, a Half-life Extended DLL3-Directed Bispecific
Antibody, in Patients With R/R SCLC
 International, open-label, first-in-human, dose-exploration/dose-expansion
phase I trial (data cutoff: Nov 3, 2020)
Patients with SCLC that
progressed/recurred after
Dose Exploration
≥ 1 platinum-based CT,
previously treated with ≥ 1 line AMG 757 0.003-30 mg IV Q2W
of systemic tx, ≥ 1 measurable with/without step dose To dose expansion
lesion, ECOG PS 0-2, adequate (n = 1-4 per dose cohort)
organ function, no untreated or Antitumor activity assessed every 7 or 9 wks
symptomatic CNS mets
(N = 52)
 Primary endpoints: safety/tolerability, MTD or RP2D

 Secondary endpoints: PK, antitumor activity
Owonikoko. WCLC 2020. Abstr OA11.03. NCT03319940. Slide credit: clinicaloptions.com

AMG 757 in R/R SCLC: Baseline Characteristics
Characteristic, n (%) Patients (N = 52)
Median age, yrs (range) 64 (32-80)
Smoking status
 Current 8 (15)
 Former 36 (69)
ECOG PS 0/1 51 (98)
Median no. prior lines of tx (range) 2 (1-6)
 1-2, n (%) 39 (75)
 ≥ 3, n (%) 13 (25)
Prior anti–PD-(L)1 23 (44)
Extensive-stage disease at diagnosis 50 (96)
Brain mets 13 (25)
Liver mets 25 (48)
Owonikoko. WCLC 2020. Abstr OA11.03. Slide credit: clinicaloptions.com

AMG 757 in R/R SCLC: Safety (Primary Endpoint)
Patients (N = 52) Worst-Grade CRS per Patients
AE, n (%) Lee 2014 Criteria, n (%) (N = 52)
All Grades Grade ≥ 3
Grade 1 17 (33)
Any TEAE 51 (98) 27 (52) Grade 2 5 (10)
Any TRAE 41 (79) 12 (23) Grade 3 1 (2)
Grade 4 0
TRAE in ≥ 10% of patients 23 (44) 1 (2)
 CRS 10 (19) 0
 Pyrexia 7 (14) 0
 Fatigue  CRS generally reversible, manageable with
5 (10) 1 (2)
 Anemia 5 (10) 0 supportive care/prophylactic corticosteroids
 Nausea
‒ Associated with fever with/without
tachycardia, nausea
 1 DLT observed (grade 5 pneumonitis)
‒ Usually occurred in cycle 1 without recurrence
 1 discontinuation due to TRAE in later cycles
‒ None led to discontinuations
Owonikoko. WCLC 2020. Abstr OA11.03. Slide credit: clinicaloptions.com
AMG 757 in R/R SCLC: Antitumor Activity
100 PD
Best Percentage Change From
Baseline in Sum of Diameters
PD
Patients
80 Response per mRECIST v1.1
(n = 51†)
60 PD
PD PD PD
40
PD PD
PD PD PD
PD PDPD
Confirmed PR, n (%) 7 (14)
PDPD PD
20 NE SD PD
SD
0
SD PD SD SD
Confirmed PR by target dose,
SDPD PD n/N (%)
-20 SD  0.3 mg 1/12 (8)
-40 SDɅ PRPD
SD  1.0 mg 1/8 (13)
PR PRSDɅ
-60 PR PR
PR PR SDɅ  3.0 mg 3/9 (33)
-80
0.003 mg 0.01 mg 0.03 mg 0.1 mg 0.3 mg PR**
 10.0 mg 2/10 (20)
1 mg 3 mg* 10 mg* 30 mg*
-100
Patients with Target Lesions and Evaluable Postbaseline Assessment, Including Unconfirmed PR, n (%) 1 (2)‡
Sum of Diameters (n = 42)
SD, n (%) 11 (22)
PR**, unconfirmed PR; SD^, initial PR not confirmed on subsequent scan; NE, PD in DCR, % 37
post-baseline scan and went off study without confirmation scan. *Step dosing.
†
Includes those treated with ≥ 1 dose of AMG 757 and with follow-up ≥ 8 wks.
‡
At target dose of 30 mg.
 Antitumor activity observed with AMG 757 during dose exploration

Owonikoko. WCLC 2020. Abstr OA11.03. Reproduced with permission. Slide credit: clinicaloptions.com
AMG 757 in R/R SCLC: Treatment Duration, DoR
6 Mos
Outcome Patients
Completed ≥ 6 mos of
10/52 (20)
treatment, n/N (%)
Patients with confirmed PR n=7

 Still receiving treatment
with ongoing response, n 4
First response (PR or better)  Median TTR, mos 1.8
Disease progression  Median DoR, mos 6.2
Death
0.003 mg  Median f/u, mos 11.5
0.01 mg
0.03 mg
0.1 mg
0.3 mg
1.0 mg
Unconfirmed PR† 3.0 mg*
10.0 mg*
30.0 mg*
0 20 40 60 80
Wks of Treatment *Step dosing. †No confirmation scan performed by cutoff.
Owonikoko. WCLC 2020. Abstr OA11.03. Reproduced with permission. Slide credit: clinicaloptions.com
Key Studies in SCLC: Summary
 RESILIENT part 1: data suggest liposomal irinotecan at the recommended dose of 70 mg/m2
exhibited promising efficacy and safety profile consistent with previous findings[1,2]
‒ ORR: 44%; median PFS: 3.98 mos; median OS: 8.08 mos
‒ Notable grade ≥ 3 TRAE: diarrhea, anemia, fatigue, hypokalemia, and hypomagnesemia
 Phase I/II of lurbinectedin + irinotecan in relapsed SCLC: according to investigators, the

combination of lurbinectedin and irinotecan showed activity in relapsed SCLC, including in
poor prognosis subgroups; toxicity is transient and manageable[3]
‒ Notable AEs included: fatigue, diarrhea, anemia, neutropenia, and thrombocytopenia
 Phase I trial of AMG 757 half-life extended bispecific: based on this recent report, AMG 757
exhibited favorable safety and durable response[4]
‒ Grade 3 TRAE in 23% of patients and only 1 patient discontinued treatment due to TRAE; CRS primarily
grade 1 or 2 (grade 3 in 1 patient)
1. Paz-Ares. WCLC 2020. Abstr FP10.04. 2. Paz-Ares. WCLC 2029. Abstr PL02.11.
3. Ponce-Aix. WCLC 2020. Abstr OA11.04. 4. Owonikoko. WCLC 2020. Abstr OA11.03. Slide credit: clinicaloptions.com
Malignant Mesothelioma
CONFIRM: Nivolumab vs Placebo in Relapsed
Malignant Mesothelioma
 Randomized, placebo-controlled phase III trial
Stratified by histology (epithelioid vs nonepithelioid)
Patients with malignant Nivolumab 240 mg IV on Day 1 Q2W

mesothelioma who (n = 221) Until PD, unacceptable
received > 1 prior line of 2:1 toxicity, withdrawal,
therapy; ECOG PS 0/1 Placebo 240 mg IV on Day 1 Q2W or 12 mos
(N = 332) (n = 111)
 Coprimary endpoints: OS, PFS (investigator reported)

 Secondary endpoints: RECIST-determined PFS, ORR, HRQoL (EQ-5D), safety
Fennell. WCLC 2020. Abstr PS01.11. Slide credit: clinicaloptions.com

CONFIRM: Baseline Characteristics
Nivolumab Placebo
Median age, yrs (IQR) 70 (65-74) 71 (65-76)
Male, n (%) 167 (76) 86 (77)
ECOG PS 0, n (%) 44 (20) 22 (20)
PD-L1 TPS* ≥ 1% (positive), n (%) 56 (37) 24 (29)
Epithelioid histology, n (%) 195 (88) 98 (88)
Pleural involvement, n (%) 211 (95) 105 (95)
Line of treatment, n (%)
 Second line 63 (29) 37 (33)
 Third line 124 (56) 66 (59)
*22C3 anti-PD-L1 antibody.

CONFIRM: Coprimary Endpoints (OS and Investigator-
Assessed PFS)
Nivolumab Placebo
Efficacy Outcome (n = 221) (n = 111) HR (95% CI) P Value
Median OS, mos 9.2 6.6 0.72 .018
 12-mos OS, % 39.5 26.9 (0.55-0.94)
Median PFS, mos 3.0 1.8 0.61
< .001
 12-mos PFS, % 14.5 4.9 (0.48-0.77)

CONFIRM: OS by PD-L1 Status and Histology
OS by PD-L1 Status Nivolumab Placebo HR (95% CI) P Value
PD-L1 Positive (n = 56) (n = 24)
Median OS, mos (95% CI) 8.0 (7.1-12.2) 8.7 (5.1-15.1) 0.95 (0.51-1.76) .864
 12-mos OS, % (95% CI) 38.6 (25.1-51.8) 43.6 (21.6-63.8)
PD-L1 Negative (n = 94) (n = 60)
Median OS, mos (95% CI) 9.0 (6.6-11.1) 6.4 (4.5-8.5)
0.74 (0.51-1.08) 0.115
 12-mos OS, % (95% CI) 36.6 (26.4-46.7) 26.0 (15.1-38.3)
OS by Histology Nivolumab Placebo HR (95% CI) P Value

Epithelioid (n = 195) (n = 98)
Median OS, mos (95% CI) 9.4 (7.7-10.9) 6.6 (5.0-8.0)
0.71 (0.53-0.95) .021
 12-mos OS, % (95% CI) 40.0 (32.6-47.3) 26.7 (17.5-36.8)
Nonepithelioid (n = 26) (n = 13)
Median OS, mos (95% CI) 5.9 (3.6-18.4) 6.7 (1.8-NA)
0.79 (0.35-1.79) .572
 12-mos OS, % (95% CI) 34.6 (15.8-54.3) 30.8 (9.5-55.4)

CONFIRM: Safety Summary
Nivolumab Placebo
AEs, n (%) (n = 221) (n = 111)
Any Grade Grade ≥ 3 Any Grade Grade ≥ 3
Any AE 207 (94) 99 (45) 104 (94) 47 (42)
Serious AEs 90 (41) 80 (36) 49 (44) 43 (39)
 No. of patients received further immunotherapy treatment: 3 (1.4%) with

nivolumab vs 14 (12.6%) with placebo
 Median (IQR) treatment duration: 84 (30-168) days with nivolumab vs 43 (29-88)
days with placebo
 Deaths related to serious AEs: 5 with nivolumab vs 4 with placebo

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CCO Conference Highlights From the

2020 World Conference on Lung Cancer

CCO Independent Conference Coverage*

Slide credit: clinicaloptions.com

 These slides may not be published, posted online, or used in

Previous systemic therapies, n (%)

Li. WCLC 2020. Abstr PS01.07. Slide credit: clinicaloptions.com

Li. WCLC 2020. Abstr PS01.07. Slide credit: clinicaloptions.com

Li. WCLC 2020. Abstr PS01.07. Slide credit: clinicaloptions.com

Patients ≥ 18 yrs of age with

 Primary endpoint: PFS  Secondary endpoints: OS, ORR, PRO, QoL,

NCT04303780. Slide credit: clinicaloptions.com

 Baseline characteristics similar between

Risk With EGFR Exon20ins vs Risk With EGFR Exon20ins vs Percentage

Sabari. WCLC 2020. Abstr OA04.04. Slide credit: clinicaloptions.com

*Excludes infusion-related reactions.

 Safety data cutoff: June 8, 2020

Sabari. WCLC 2020. Abstr OA04.04. Slide credit: clinicaloptions.com

Helical region (762-766)

40 Not detected by ctDNA

PD: Pre Post data cutoff

Zhou. WCLC 2020. Abstr OA04.03. Slide credit: clinicaloptions.com

Zhou. WCLC 2020. Abstr OA04.03. Slide credit: clinicaloptions.com

Target Lesion Diameter (%)

Change From BL in Sum of

 In PPP cohort, 82% of patients  In EXCLAIM cohort, 80% of

PFS (N = 114) DoR (n = 30)

DoR Probability (%)

PFS (N = 96) DoR (n = 22)

DoR Probability (%)

*Full analysis set data.

Nakagawa. WCLC 2020. Abstr OA04.05. Slide credit: clinicaloptions.com

Nakagawa. WCLC 2020. Abstr OA04.05. Slide credit: clinicaloptions.com

 Primary endpoints: MTD, safety,  Secondary endpoints: efficacy and PK

Spira. WCLC 2020. Abstr OA03.03. NCT03401385. Slide credit: clinicaloptions.com

Spira. WCLC 2020. Abstr OA03.03. Slide credit: clinicaloptions.com

Spira. WCLC 2020. Abstr OA03.03. Slide credit: clinicaloptions.com

 Consistent PK throughout 3 treatment cycles at each dose

Spira. WCLC 2020. Abstr OA03.03. Slide credit: clinicaloptions.com

 Current analysis evaluated ORR, PFS, OS in KRAS-WT, KRAS-mut, TP53-WT,

Li. WCLC 2020. Abstr OA07.06. Slide credit: clinicaloptions.com

3DMed 37 Anti–PD-1/PD-L1 First to subsequent Real world ORR, PFS, OS

Li. WCLC 2020. Abstr OA07.06. Slide credit: clinicaloptions.com

Li. WCLC 2020. Abstr OA07.06. Slide credit: clinicaloptions.com

TP53 + KRAS 76 50.0 10.48 13 7.7 2.86

Li. WCLC 2020. Abstr OA07.06. Slide credit: clinicaloptions.com

*Assessed centrally using the PD-L1 IHC 22C3 pharmDx assay.

 Primary endpoints: OS and PFS per RECIST v1.1 by BICR

Characteristic Pembrolizumab + Ipilimumab Pembrolizumab + Placebo

Boyer. WCLC 2020. Abstr PS01.09. Slide credit: clinicaloptions.com

*Reported using 129 for each arm.

Boyer. WCLC 2020. Abstr PS01.09. Slide credit: clinicaloptions.com

Boyer. WCLC 2020. Abstr PS01.09. Slide credit: clinicaloptions.com

Lai. WCLC 2020. Abstr OA01.06. Slide credit: clinicaloptions.com

EGFR mutation, n (%)

Lai. WCLC 2020. Abstr OA01.06. Slide credit: clinicaloptions.com

Lai. WCLC 2020. Abstr OA01.06. Slide credit: clinicaloptions.com

Lai. WCLC 2020. Abstr OA01.06. Slide credit: clinicaloptions.com

 1 pneumonitis event (grade 1) in nivo arm

Lai. WCLC 2020. Abstr OA01.06. Slide credit: clinicaloptions.com

Kilickap. WCLC 2020. Abstr OA01.03. Slide credit: clinicaloptions.com

Tumor Size (LOCF)

20 13.1-23.2) (95% CI:

12-Mo PFS, % (95% CI)