IMMUNOTHERAPY:

A NEW ERA IN CANCER

THERAPY

Dr. W MOUKADEM
20/10/2017
 Evolution of Cancer Therapy

Historical1,2 1990s1,3 Today4

RATIONAL USE OF
CHEMOTHERAPY
MULTIPLE MODALITIES
TARGETED THERAPY
Targets rapidly dividing cells
Can leverage strengths of
(cell cycle)
each approach

G2/M
Checkpoint M

G2 G1 G0

Mutation

G1/S
Checkpoint

Cell cycle image reprinted with permission from Samarasinghe B. The hallmarks of cancer: 2 – insensitivity to antigrowth signals. Scientific
American website. http://blogs.scientificamerican.com/guest-blog/the-hallmarks-of-cancer-2-insensitivity-to-antigrowth-signals/. Accessed 8 June
2016. Multiple modalities image adapted with permission from Hanahan D, Weinberg RA. Cell. 2011;144(5):646–674.
1. American Cancer Society. A History of Cancer. http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/index?sitearea. Accessed 18 January 2016. 2.
Samarasinghe B. The hallmarks of cancer: 2 – insensitivity to antigrowth signals. Scientific American website. http://blogs.scientificamerican.com/guest-
blog/the-hallmarks-of-cancer-2-insensitivity-to-antigrowth-signals/. Accessed 8 June 2016. 3. Boolell V et al. Cancers (Basel). 2015;7(3):1815–1846.
4. Hanahan D, Weinberg RA. Cell. 2011;144(5):646–674.
The Role of the Immune System in
Advanced Cancer
 Antitumor Immune Response

T-cell–mediated immune response1,2

Tumor- Antitumor effector
specific mechanisms
antigens
Dendritic cell

Tumor cell Naïve cytotoxic Activated cytotoxic Tumor cell

T cell T cell

• The body’s immune response can detect and destroy

tumor cells through activated T cells and other
mechanisms1
• Tumor cells express multiple antigens that are not
expressed in normal tissue2

Image adapted from Chen DS et al. Immunity. 2013;39(1):1–10. Reprinted with permission from Elsevier.

1. May KF Jr et al. In: Prendergast GC et al. Cancer Immunotherapy. 2nd ed. Philadelphia, PA: Elsevier; 2013:101–113.
2. Chen DS et al. Immunity. 2013;39(1):1–10.
 Evading Immune Destruction
Is a Hallmark of Cancer1

Emerging Hallmarks
Activated
Tumor cells can T cells Tumor cells can
reprogram cellular evade detection and
metabolism to gain destruction by the
energy immune system

TUMOR
Tumor cells invade and
Tumor cells divide
metastasize to other
without control
tissues
Tumor cells
sustain
Tumor cells Tumor cells encourage
proliferative
evade growth growth of new blood
signaling
suppressors Tumor cells vessels
resist cell death

Established Hallmarks
Image from Hanahan D, Weinberg RA. Cell. 2011;144(5):646–674. Reprinted with permission from Elsevier.

1. Hanahan D, Weinberg RA. Cell. 2011;144(5):646–674.

Tumors Exploit Immune Checkpoint Pathways
as One Mechanism of Immune Evasion

• Normal immune Immune checkpoint receptors2

checkpoint pathway =
elaborate series of
cellular interactions that
prevent excessive T-cell
activity1
• T-cell responses are
regulated by a number
of activating and
inhibitory interactions1

Abs = antibodies; BTLA = B and T lymphocyte attenuator; CD = cluster of differentiation; CTLA-4 = cytotoxic T lymphocyte-associated protein-4; GITR = glucocorticoid
induced tumor necrosis factor-related protein; HVEM = herpes virus entry mediator; LAG-3 = lymphocyte-activation gene 3; PD-1 = programmed death receptor-1; TIM-
3 = T-cell immunoglobulin domain and mucin domain-3; VISTA = V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation.
Image reprinted with permission from Mellman I et al. Nature. 2011;480(7378):480–489.

1. Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.

2. Mellman I et al. Nature. 2011;480(7378):480–489.
 In Advanced Cancer, the PD-1 Pathway May
Be Exploited to Evade the Immune Response1,2
Antigen Antigen

TCR MHC TCR MHC

PD-L1 PD-L1
PD-1 PD-1

PD-L2
PD-L2

Activated cytotoxic Inactivated cytotoxic

Tumor cell/APC Tumor cell/APC
T cell T cell

• Emerging research has identified PD-1 as a key immune checkpoint pathway

involved in inhibiting the T-cell–mediated immune response
• Tumor cells can downregulate T-cell activity by exploiting the PD-1
checkpoint
pathway through expression of the PD-1 ligands, PD‐L1 and PD‐L2
• PD-L1 and PD-L2 engage the PD-1 receptor on T cells to inactivate them, which
may allow tumor cells to evade the immune response
APC = antigen-presenting cell; MHC = major histocompatibility complex; NSCLC = non‒small cell lung cancer; PD-1 = programmed death receptor-1;
PD-L1 = programmed death ligand 1; PD-L2 = programmed death ligand 2; TCR = T-cell receptor.
Image adapted with permission from Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.
1. Keytruda Lebanon Summary of Product Characteristics July 2017 2. Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.
About KEYTRUDA™ (Pembrolizumab)
 KEYTRUDA™ (Pembrolizumab)1–3

• KEYTRUDA is a high-affinity antibody against PD-1, which

exerts dual ligand blockade of the PD-1 pathway,
including PD-L1 and PD-L2, on antigen-presenting or
tumor cells.

Mouse variable (CDR) sequences

Variable grafted onto human framework Variable

Constant Constant

Parental antibody MK-3475

Mouse IgG1 Human IgG4
KD: ~28 pM KD: ~29 pM
IC50: ~800 pM IC50: ~600 pM
EC50: ~118 pM EC50: ~70 pM

CDR = complementarity-determining region; EC50 = half maximal effective concentration; IC50 = half maximal inhibitory concentration;
IgG1 = immunoglobulin G1; IgG4 = immunoglobulin G4; PD-1 = programmed death receptor-1; PD-L1 = programmed death ligand 1;
PD-L2 = programmed death ligand 2.
1. Keytruda Lebanon Summary of Product Characteristics July 2017
2. Hamid O et al. N Engl J Med. 2013;369(2):134–144.
3. US Food and Drug Administration. Center For Drug Evaluation and Research: BLA 125514 Pharmacology Review(s). 28 February 2014.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125514Orig1s000PharmR.pdf. Accessed 17 May 2016.
 PD-1 Receptor Blockade With
KEYTRUDA™ (Pembrolizumab)1,2
Antigen

MHC
TCR

KEYTRUDA

PD-1 PD-L1
PD-1 PD-L1

PD- PD-L2
Inactivated
Activated
Tumor cell
cytotoxic T cell L2

• By inhibiting the PD-1 receptor from binding to its ligands,

KEYTRUDA reactivates tumor-specific cytotoxic T lymphocytes
in the tumor microenvironment and reactivates antitumor
immunity.2

MHC = major histocompatibility complex; PD-1 = programmed death receptor-1; PD-L1 = programmed death ligand 1; PD-L2 = programmed death
ligand 2; TCR = T-cell receptor.
1. Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.
2. Keytruda Lebanon Summary of Product Characteristics July 2017
PD-L1 Expression Matters
 PD-L1 Expression Testing Determines Patients
Most Likely to Benefit From KEYTRUDA™
(pembrolizumab)1
A validated PD-L1 IHC test has been developed to optimally
determine PD-L1 expression status.2
•PD-L1 expression level is measured using TPS, the percentage of tumor cells
staining for PD-L1 (0%–100%).3,4
•PD-L1 expression level can be interpreted as no expression (TPS <1%), any
expression (TPS 1%–100%), or high expression (TPS 50%–100%).3,4
Examples of Staining Results4
<1% 1% 50% 100%

No PD-L1 expression
High PD-L1 expression
Any PD-L1 expression

Stains are 20× magnification; reproduced with permission of Dako Denmark A/S, a subsidiary of Agilent Technologies, Inc., Santa Clara, California, USA.
All rights reserved.
IHC = immunohistochemistry; PD-L1 = programmed death ligand 1; TPS = tumor proportion score.
1. Herbst RS et al. Lancet. 2016;387(10027):1540–1550. 2. Dolled-Filhart M et al. Arch Pathol Lab Med. 2016;140(11):1243–1249.
3. PD-L1 IHC 22C3 pharmDx IVD [package insert]. Dako. P03951_04/SK00621-5/2016.10. 4. Dako Denmark A/S. PD-L1 IHC 22C3 pharmDxTM Interpretation Manual.
 KEYTRUDA™ (pembrolizumab):
Indication and Usage
Melanoma
 For the treatment of patients with unresectable or
metastatic melanoma. (1.1)
Non-Small Cell Lung Cancer (NSCLC)
 as a single agent for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression
[(Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor
aberrations. (1.2)
 as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as
determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with
EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations
prior to receiving KEYTRUDA. (1.2)
 in combination with pemetrexed and carboplatin, as first-line treatment of patients with metastatic nonsquamous NSCLC.
This indication is approved under accelerated approval based on tumor response rate and progression-free survival.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the
confirmatory trials. (1.2)
Head and Neck Squamous Cell Cancer (HNSCC)
 for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing
chemotherapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued
approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. (1.3)
Classical Hodgkin Lymphoma (cHL)
 for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after 3 or more prior lines of
therapy. This indication is approved under accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in
the confirmatory trials. (1.4)
Urothelial Carcinoma
 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-
containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration
of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in
confirmatory trials. (1.5)
 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or
following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-
containing chemotherapy. (1.5)

ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; PD-L1 = programmed death ligand 1.
1. Keytruda Lebanon Summary of Product Characteristics July 2017
Keytruda in Non Small Cell
Lung Cancer

1
 Global Incidence of Lung Cancer

Worldwide Incidence of Lung Cancer (2012)

• Lung cancer for Men and Women
Global Region Estimated Estimated
– Most common cancer Incidence2,a Mortality3,a
in the world for several (%) (%)
decades1 Northern America 68.4 53.5
– 1.8 million new cases Northern Europe 60.0 52.3
estimated in 2012 Southern Europe 58.2 50.6
(12.9% of the total)1 Australia/New Zealand 48.8 36.1
– Most common cause Asia 24.6 22.0
of death from cancer Caribbean 22.6 21.0
worldwide (1.59 million
South America 16.0 14.0
deaths, 19.4% of the
Central America 6.7 6.0
total)1
Africa 2.8 2.5
aCrude and age-standardized rates per 100,000.2,3

1. GLOBOCAN 2012: Cancer fact sheet: lung cancer. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed July 31, 2015.
2. GLOBOCAN 2012: Lung – Estimated incidence, all ages: both sexes. http://globocan.iarc.fr/old/summary_table_site- html.asp?
selection=15110&title=Lung&sex=0&type=0&window=1&africa=1&america=2&asia=3&europe=4&oceania=5&build=6&sort=0&submit=%C2%A0Execute%C2%A0.
Accessed July 31, 2015.
3. GLOBOCAN 2012: Lung – Estimated mortality, all ages: both sexes. http://globocan.iarc.fr/old/summary_table_site- html.asp?
selection=15110&title=Lung&sex=0&type=1&window=1&africa=1&america=2&asia=3&europe=4&oceania=5&build=6&sort=0&submit=%C2%A0Execute.
Accessed July 31, 2015.
 Unmet Needs for Treatment
of Advanced NSCLC

NSCLC Stage Distribution 5-Year Observed Survival Rate

in the United States1,a in the United States2,b
100
90

Localized 80

19% 70
60
49%
45%
Distant 50

55% Regional 40
30% 31%
24% 30
20 14%
10 5%
1%
0
Unstaged IA IB IIA IIB IIIA IIIB IV
3%
Stage
Based on United States Surveillance, Epidemiology, and End Results (SEER) data from 2005–2011.
a

Based on survival rates published in 2007. The data were calculated from the National Cancer Institute’s SEER database, based on people who were diagnosed with
b

NSCLC between 1998–2000.

NSCLC = non–small cell lung cancer.

1. Howlader N et al. SEER Cancer Statistics Review, 1975-2012. National Cancer Institute. Bethesda, MD,
http://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data submission, posted to the SEER website, April 2015
2. American Cancer Society. Lung Cancer (Non-Small Cell).
rates. Accessed October 27, 2015.
http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-
 Current Treatment Overview
of Advanced NSCLC
Chemotherapy Targeted Therapy Immune Checkpoint Inhibitors
G2/M
Checkpoint M

G2 G1
G0

Mutation

G1/S
Checkpoint

Standard of Care EGFR/ALK+ Patients 2L All-Comers or PD-L1+

Patients
• Used across all lines of • Mutational status rates and • Indications/approvals vary by
therapy1 testing vary by market/region market/region
• Commonly used agents: (1L) • Commonly used agents: • Agents: nivolumab
platinum doublets, (2L) single- erlotinib, gefitinib, afatinib (all-comers), pembrolizumab
agent docetaxel, pemetrexed, (EGFR+), crizotinib, ceritinib (PD-L1+)6,7
gemcitabine1 (ALK+)1 • New to market; target
• Backbone of therapy for • Improved outcomes in patients immunosuppressive
patients with lung cancer2 with mutations3–5 mechanisms8
ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; NSCLC = non–small cell lung cancer; PD-1 = programmed death receptor-1; PD-L1 = programmed death ligand 1.
Cell cycle image reprinted with permission from Samarasinghe B. The hallmarks of cancer: 2 – insensitivity to antigrowth signals. Scientific American website.
http://blogs.scientificamerican.com/guest-blog/the-hallmarks-of-cancer-2-insensitivity-to-antigrowth-signals. Immune checkpoint inhibitors image adapted from Chen DS et al. Immunity.
2013;39(1):1–10. Reprinted with permission from Elsevier.
1.Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2016. © 2016 National Comprehensive Cancer
Network, Inc. All rights reserved. Accessed 14 January 2016. To view the most recent and complete version of the guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE
CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN® content are trademarks owned by the National Comprehensive Cancer Network, Inc.
2. Carrizosa DR et al. Oncology (Williston Park). 2013;27(5):396-404. 3. Kwak EL et al. N Engl J Med. 2010;363(18):1693–1703. 4. Maemondo M et al. N Engl J Med. 2010;362(25):2380–
2388.
5. Zhou C et al. Lancet Oncol.
Oncol. 2011;12(8):735–742.
2015;42(Suppl 6. Keytruda SmPC Lebanon July 2017 7. OPDIVO US Prescribing Information. Princeton, NJ: Bristol-Myers Squibb; January 2016.
2):S11–S18.
 KEYNOTE-024:Study of
KEYTRUDA vs chemotherapy in
first-line treatment of patients
with NSCLC with TPS ≥50%1

1.Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYNOTE-024: KEYTRUDA™ (Pembrolizumab) vs
Chemotherapy - Study Design1

• Randomized, open-label, multicenter trial of patients with

previously untreated metastatic NSCLC whose tumors expressed
high levels of PD-L1 (TPS ≥50%)1
Patient Key Eligibility
Criteria KEYTRUDA 200 mg Treatment continued
until disease
every 3 weeks
• Stage IV NSCLC Tumor progression or
(n=154) unacceptable toxicity
• PD-L1 TPS ≥50% response
• No prior systemic R assessed
treatment for 1:1 at
metastatic NSCLC Investigator’s choice 9-week Patients on
• No EGFR or ALK intervals chemotherapy
platinum-containing
genomic tumor who experienced
chemotherapy
aberrations PD were offered
• ECOG PS 0 or 1 (n=151) KEYTRUDA

• Primary end point was progression-free survival (PFS) as assessed by blinded

independent central review using RECIST v1.1.1
• Secondary end points were overall survival (OS) and objective response rate
(ORR) as assessed by blinded independent central review using RECIST v1.1.1
ALK = anaplastic lymphoma kinase; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth
factor receptor; NSCLC = non–small cell lung cancer; PD = progressive disease; PD-L1 = programmed death ligand 1; R = randomized;
RECIST = Response Evaluation Criteria in Solid Tumors version 1.1; TPS = tumor proportion score.
1. Reck M et al. N Engl J Med. 2016;375(14):1–11.
 KEYNOTE-024: KEYTRUDA™ (pembrolizumab)
vs Chemotherapy PFS (Primary End Point)1
• Superior PFS with KEYTRUDA 200 mg Q3W vs chemotherapy
(HR 0.50, 95% CI, 0.37–0.68; P<0.001) in patients with PD-L1 TPS ≥50%
– 50% reduction in risk of disease progression or death with KEYTRUDA vs
chemotherapy1
Kaplan-Meier Estimates of PFS in ITT Population
100
HR Median, mo 6-mo rate
90 Treatment Arm (95% CI) (95% CI) (95% CI)
KEYTRUDA 0.50 (0.37–0.68) 10.3 (6.7– 62.1%
80
(n=154) P<0.001 NR) (53.8–
6.0 69.4)
70 Chemotherapy
–
(n=151) (4.2–6.2) 50.3%
(41.9–
60
PFS (%)

58.2)

50

40

30

20

10

0
0 3 6 9 12 15 18
No. at risk Time, months
KEYTRUDA 200 mg Q3W 154 104 89 44 22 3 1

Chemotherapy 151 99 70 18 9 1 0
CI = confidence interval; HR = hazard ratio; ITT = intent-to-treat; mo = month; NR = not reached; PD-L1 = programmed death ligand 1;
PFS = progression-free survival; Q3W = every 3 weeks; TPS = tumor proportion score.
1. Reck M et al. N Engl J Med. 2016;375(14):1–11.
 KEYNOTE-024: KEYTRUDA™ (pembrolizumab)
vs Chemotherapy OS (Secondary End Point)1
• Superior OS with KEYTRUDA 200 mg Q3W vs chemotherapy
(HR 0.60, 95% CI, 0.41–0.89; P=0.005) in patients with PD-L1 TPS ≥50%
– 40% reduction in risk of death with KEYTRUDA vs
chemotherapy

Kaplan-Meier
100 Estimates of OS in ITT Population1,2

90 80%

80

70
72%
60
OS (%)

50

40
HR (95% CI) Median, mo 6-mo rate
30 (95% CI) (95% CI)
Treatment Arm 0.60 (0.41–
0.89) Not reached 80.2%
20 KEYTRUDA
P=0.005 (72.9–
(n=154)
85.7)
10 Chemotherapy – Not reached
72.4%
(n=151)
(64.5–
0 78.9)
0 3 6 9 15 18 21
12
No. at risk
KEYTRUDA 200 mg Q3W 154 Time, months
136 121 82 39 11
2 0
Chemotherapy 151 123 106 64 34 7 1 0
CI = confidence interval; HR = hazard ratio; ITT = intent-to-treat; mo = month; OS = overall survival; PD-L1 = programmed death ligand 1;
Q3W = every 3 weeks; TPS = tumor proportion score.
1. Reck M et al. N Engl J Med. 2016;375(14):1–11. 2. Keytruda Summary of Product Characteristics Lebanon July 2017
 KEYNOTE-024: KEYTRUDA™ (Pembrolizumab)
vs Chemotherapy ORR (Secondary End Point)1

• ORR was greater with KEYTRUDA 200 mg Q3W vs chemotherapy in

patients with PD-L1 TPS ≥50%.1

100
44.8%
50 (n=69/154)
45
95% CI: 36.8–53.0
40
27.8%
ORR (%)

35 (n=42/151)
30 95% CI: 20.8–35.7
25
20
15
10
5
0
KEYTRUDA Chemotherapy
200 mg Q3W

• Median duration of response was not reached (range, 1.9+ to 14.5+ months) in
the KEYTRUDA group vs 6.3 months (range, 2.1+ to 12.6+ months) in the
chemotherapy group.1
CI = confidence interval; ORR = objective response rate; PD-L1 = programmed death ligand 1; Q3W = every 3 weeks; TPS = tumor
proportion score.
1. Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYNOTE-024: KEYTRUDA™ (pembrolizumab) vs
Chemotherapy Crossover and Follow-Up

• Survival was longer with KEYTRUDA despite the low number of

deaths observed and the potentially confounding effect of
crossover from the chemotherapy to the KEYTRUDA group.1
– 43.7% of patients from the chemotherapy group crossed over to the
KEYTRUDA group.
– Of the patients who crossed over, 57.6% were still receiving
KEYTRUDA at the time of data cutoff (9 May 2016).
• Median duration of follow-up was 11.2 months (range, 6.3–19.7
months).1
– 48.1% of patients in the KEYTRUDA group and 10.0% of patients in
the chemotherapy group were still receiving assigned treatment.

Q3W = every 3 weeks.

1. Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYTRUDA™ (pembrolizumab):
Summary and Conclusions

• KEYTRUDA is the only anti–PD-1 approved for first-line treatment of

patients with metastatic NSCLC with high PD-L1 expression
(TPS ≥50%).1
• In the KEYNOTE-024 study, superior OS was observed with KETYRUDA
vs chemotherapy in patients with PD-L1 TPS ≥50%.1
– 40% reduction in risk of death with KEYTRUDA 200 mg Q3W vs
chemotherapy (HR 0.60, 95% CI, 0.41–0.89; P=0.005)
– 43.7% of patients in the chemotherapy arm crossed over to receive
KEYTRUDA after disease progression.
• Superior PFS was also observed with KEYTRUDA vs chemotherapy in
patients with PD-L1 TPS ≥50%.1
– 50% reduction in risk of disease progression or death with KEYTRUDA
200 mg Q3W vs chemotherapy (HR 0.50, 95% CI, 0.37–0.68; P<0.001)
• Immune-mediated AEs occurred with KEYTRUDA; most were Grade 1 or
2, and none led to death.1
Continued on next slide
AE = adverse event; CI = confidence interval; HR = hazard ratio; NSCLC = non–small cell lung cancer; OS = overall survival; PD-1 =
programmed death receptor-1; PD-L1 = programmed death ligand 1; PFS = progression-free survival; Q3W = every 3 weeks; TPS = tumor
proportion score.
1. Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYTRUDA™ (Pembrolizumab): Only Single Agent
Anti–PD-1 to Show Unprecedented Survival in
First-line NSCLC With High PD-L1 Expression1

• The KEYNOTE-024 study of KEYTRUDA vs chemotherapy in first-

line treatment of patients with NSCLC with TPS ≥50% met its
primary end point: KEYTRUDA was superior compared with
chemotherapy for both the primary end point (PFS) and secondary
end point (OS).1

• Based on these results, an independent Data Monitoring

Committee (DMC) recommended that the trial be stopped, and
that patients receiving chemotherapy be offered the opportunity to
receive KEYTRUDA.1

NSCLC = non–small cell lung cancer; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival; TPS = tumor
proportion score.
1.Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 National Comprehensive Cancer Network®
(NCCN®) Recommendation

First-line Therapy1

PD-L1 expression positive

Pembrolizumab2
(≥50%) and EGFR, ALK,
(category 1)
ROS1 negative or unknown

• The NCCN panel recommends Pembrolizumab (KEYTRUDA®) as

category 1 for first-line treatment of patients with metastatic non-
squamous or squamous NSCLC whose tumors are PD-L1–positive
(TPS ≥50%) and EGFR-, ALK-, and ROS1-negative or unknown.1

ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; NSCLC = non–small cell lung cancer;
PD-L1 = programmed death ligand 1; ROS1 = ROS proto-oncogene 1, receptor tyrosine kinase; TPS = tumor proportion score.
1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non–Small Cell Lung Cancer V.3.2017.
© 2016 National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed 23 November 2016. To view the most recent and complete
version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other
NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.
2. Reck M et al. N Engl J Med. 2016;375(14):1–11.
 KEYNOTE-024: KEYTRUDA™ (pembrolizumab) vs
Chemotherapy Immune-mediated AEs1,a

10
Immune-mediated AEs
9.1 occurred with KEYTRUDA
9
7.8 • Most were Grade 1 or 2
8
• No Grade 5 events
Grade Grade
Incidence (%)

7
6
5.8 1-2 ≥3

5 4.5
3.9 3.9
4
3 2.6 2.6
1.9 1.9
2
1.3
1 0.6 0.6
0.6 0.6 0.6 0.6 0.6 0.6
0 0 0 0 0
0

aThe immune-mediated events, both those that were and those that were not attributed to study treatment by the investigator, are listed in
descending order of frequency in the KEYTRUDA group. In addition to specific preferred terms, related terms are also included.
AE = adverse event; T1DM = type 1 diabetes mellitus.
1. Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYNOTE-024: KEYTRUDA™ (pembrolizumab) vs
Chemotherapy Treatment-Related AEs1,a–c
50
Grade Grade
45 43.3 44 1–2 ≥3
40
KEYTRUDA
Chemotherapy
Incidence (%)

35

30 28.7
26
25 22.7
19.3 20
20

15 14.3 13.3 13.3

9.7 10.4 10.4
10 9.1
5.2 5.3
5 3.3 3.9 2.6
2 1.9 2.7 1.3
0 1.3 0 0.6 0 0.6 0.7 0 0
0

Continued on next slide

aAssessed in the as-treated population. The as-treated population included all patients who received at least one dose of a trial treatment. For the
patients in the chemotherapy group who crossed over to the KEYTRUDA group after disease progression, only events that occurred during
treatment with the assigned chemotherapy regimen are included. bEvents were attributed to treatment by the investigator and are listed as indicated
by the investigator on the case-report form. Although decreased neutrophil count and neutropenia may reflect the same condition, they were listed
by the investigators as two distinct events; this is also the case for decreased platelet count and thrombocytopenia. cEvents are listed in descending
order of frequency in the total population.
AE = adverse event.
1. Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYNOTE-024: KEYTRUDA™ (pembrolizumab) vs
Chemotherapy Treatment-Related AEs1,a–c (continued)
50
Grade Grade
45 1–2 ≥3
40
KEYTRUDA
Chemotherapy
Incidence (%)

35

30

25

20

15 13.3
11.3 12 12 11.3
10 10.7 10
10
6 5.3
5 3.9 4
2.6 1.3 1.9 2
0 0 0 0 0 0 0.7 0 0 0.6 0 0.6 0 0
0
0 0

aAssessed in the as-treated population. The as-treated population included all patients who received at least one dose of a trial treatment. For the
patients in the chemotherapy group who crossed over to the KEYTRUDA group after disease progression, only events that occurred during
treatment with the assigned chemotherapy regimen are included. bEvents were attributed to treatment by the investigator and are listed as indicated
by the investigator on the case-report form. Although decreased neutrophil count and neutropenia may reflect the same condition, they were listed
by the investigators as two distinct events; this is also the case for decreased platelet count and thrombocytopenia. cEvents are listed in descending
order of frequency in the total population.
AE = adverse event.
1. Reck, Martin, et al. "Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer." N Engl J Med 2016.375 (2016): 1823-1833.
 KEYNOTE-021G: KEYTRUDA™ (pembrolizumab) +
Chemotherapy vs Chemotherapy Study Design

• Randomized, controlled, phase 2 study, Naïve NSCLC non

Squamous, Irrelevant of PDL1
Patient Key Eligibility
Criteria 4 cycles:
Pembrolizumab 200 mg /30 min, +
• No previous systemic treatment for Pemetrexed 500 mg/m /10 min+
Maintenance:
histologically or cytologically
Carboplatin area under curve 5 mg/mL per Pembro izumab200mg/ 24mo
confirmed non-squamous
• Stage IIIB or IV NSCLC min/15–60 min IV Q3W Pemetrexed Indefinitely
• Absence of targetable EGFR N=60
mutations or ALK translocations.
• ECOG PS of 0 or 1 1:1
R
• At least one measurable lesion 1:1
assessed per RECIST version 1.120 4 cycles:
by the investigator
• Provision of a tumor biopsy sample Pemetrexed 500 mg/m /10 min+ Carboplatin area
for assessment of PD-L1 expression under curve 5 mg/mL per min/15–60 min IV Q3W
N=63

• Primary end point was objective response rate (ORR) defined as the percentage of
patients with radiologically confirmed complete or partial response according to
RECIST version 1.1 assessed by masked, independent central review
• Secondary end points were overall survival (OS) , Progression free survival (PFS) and
Safety as assessed by blinded independent central review using RECIST v1.1.1

1. Langer, Corey J., et al. "Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort
of the open-label KEYNOTE-021 study." The lancet oncology 17.11 (2016): 1497-1508.
 KEYNOTE-021G: KEYTRUDA™ (Pembrolizumab) +
Chemotherapy vs Chemotherapy: Primary End Point ORR1

1. Langer, Corey J., et al. "Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell
lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study." The lancet oncology 17.11 (2016): 1497-1508.
 KEYNOTE-021G: KEYTRUDA™ (Pembrolizumab) +
Chemotherapy vs Chemotherapy PFS (Secondary End Point)1

Progression-free survival 1
• Significantly longer with Pembrolizumab
plus chemotherapy compared with
chemotherapy alone (HR 0·53 [95% CI 0·31–
0·91]; p=0·010)

• Median progression-free survival was 13·0

months (95% CI 8·3 to not reached) for
Pembrolizumab plus chemotherapy and 8·9
months (4·4–10·3) for chemotherapy alone.

• Estimated 6-month progression-free

survival was 77% (95% CI 64–86) for
Pembrolizumab plus chemotherapy and
63% (49–74) for chemotherapy

Figure 3: Kaplan-Meier estimates of progression-free survival (A) and overall survival (B)
Progression-free survival assessed per Response Evaluation Criteria In Solid Tumors version 1.1 by masked, independent central radiology review in the intention-to-treat population.

1. Langer, Corey J., et al. "Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised,
 KEYTRUDA™ (pembrolizumab):
Summary and Conclusions1

• KEYTRUDA is the only anti–PD-1 approved for first-line treatment of

patients with metastatic NSCLC non squamous irrelevant of PDL1
Expression2.
• In the KEYNOTE-021G study, superior ORR was observed with
KETYRUDA + Chemotherapy vs chemotherapy in patients.
• 55% vs 29% (95%CI, P value 0.0016)1
• Superior PFS was also observed with KEYTRUDA + Chemotherapy vs
chemotherapy in patients irrelevant of PDL1 expression.1
– Median progression-free survival in the Pembrolizumab plus chemotherapy
group was 13·0 months (95% CI 8·3 to not reached).

1. Langer, Corey J., et al. "Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell
lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study." The lancet oncology 17.11 (2016): 1497-1508.
2. Keytruda Lebanon Summary of Product Characteristics July 2017
Keynote 21 G: Carboplatin and Pemetrexed with or without
Pembrolizumab for advanced, non-squamous non-small-cell lung cancer:
a randomised, phase 2 cohort of the open-label KEYNOTE-021 study

• The KEYNOTE-021G study of KEYTRUDA vs chemotherapy in

first-line treatment of patients with Non Squamous NSCLC
regardless of TPS met its primary end point: KEYTRUDA+
Carboplatin + Pemetrexed was superior compared with
chemotherapy for both the primary end point (ORR) and
secondary end point (PFS), (DOR), (OS).1
• Combination of Pembrolizumab, Carboplatin, and Pemetrexed
could be an effective and tolerable first-line treatment option for
patients with advanced non-squamous NSCLC.

NSCLC = non–small cell lung cancer; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival; TPS =
tumor proportion score.
1.Langer, Corey J., et al. "Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2
cohort of the open-label KEYNOTE-021 study." The lancet oncology 17.11 (2016): 1497-1508.
 Clinical Trials Evaluating KEYTRUDATM
(pembrolizumab)

KEYNOTE-010: Study of KEYTRUDA

Versus Docetaxel in Patients With Previously
Treated Advanced NSCLC Whose
Tumors Express PD-L1.

1. Herbst RS et al. Lancet. 2016;387(10027):1540–1550.

 KEYNOTE-010: KEYTRUDATM (Pembrolizumab) vs
Docetaxel Study Design1,2

• Multicenter, open-label, phase 2/3 trial of patients with previously treated advanced
NSCLC and PD-L1-positive tumors randomized to receive either single-agent
KEYTRUDA or docetaxel
Patients (N=1033)
KEYTRUDA
• Advanced NSCLC 2 mg/kg
• PD-L1 TPS ≥1% every 3 weeks
(n=344)
• Confirmed PD after ≥2 cycles
platinum-doublet chemotherapy and Treatment until
if appropriate, targeted therapy for KEYTRUDA
disease
ALK or EGFR mutations R 10 mg/kg
progression or
• ECOG performance status 0-1 1:1:1 every 3 weeks
(n=346)
unacceptable
• No active brain metastases toxicity
• No active autoimmune disease
Docetaxel
• No receipt of >30 Gy of thoracic 75 mg/m2
radiation within the prior 26 weeks every 3 weeks
• No ILD or pneumonitis requiring (n=343)
systemic steroids

• Co-primary outcomes: Overall survival (OS) and progression-free survival (PFS) both in
the total population (TPS ≥1%) and in patients with TPS ≥50%
• Secondary outcomes: Overall response rate, duration of response
ALK = anaplastic lymphoma kinase; ECOG = Eastern Cooperative Oncology Group; EGFR = epidermal growth factor receptor; ILD = interstitial lung disease; NSCLC = non–small cell lung
cancer; PD = progressive disease; PD-L1 = programmed death ligand 1; TPS = tumor proportion score.
1. Herbst RS et al. Lancet. 2016;387(10027):1540–1550
2. Keytruda Lebanon Summary of Product Characteristics July 2017
 KEYNOTE-010: KEYTRUDATM (pembrolizumab) vs Docetaxel
Overall Survival (Co-primary End Point)a
• OS was significantly improved with KEYTRUDA 2 mg/kg Q3W vs
docetaxel in patients with any level of positive PD-L1 expression1,2
PD-L1 TPS ≥1% PD-L1 TPS ≥50%
KEYTRUDA Docetaxel KEYTRUDA Docetaxel
2 mg/kg Q3W 75 2 mg/kg Q3W 75
100 Median OS 10.4 mo mg/m
8.5 mo
2 100 Median OS 14.9 mo mg/m 2
8.2 mo
90 (95% CI) (9.4–11.9) (7.5–9.8) 90 (95% CI) (10.4–NR) (6.4–10.7)
HR (95% CI) 0.71 (0.58–0.88); P<0.001 80 HR (95% 0.54 (0.38–0.77); P<0.001

Overall Survival (%)

80
Overall Survival (%)

CI)
70 70
60 60
43% 50
50
40 40
30 35% 30
20 20
10 10
0 0
0 5 10 12 15 20 25 0 5 10 15 20 25
Number at risk Time (months) Number at risk
Time (months)
KEYTRUDA 2 mg/kg Q3W 344 259 115 49 12 0 KEYTRUDA 2 mg/kg Q3W 139 110 51 20 3 0
Docetaxel 75 mg/m2 343 212 79 33 1 0 Docetaxel 75 mg/m2 152 90 38 19 1 0

For KEYTRUDA 10 mg/kg Q3W (TPS≥1%), 1-year estimated OS For KEYTRUDA 10 mg/kg Q3W (TPS≥50%), median OS was 17.3
was 52%, median OS was 12.7 mo (95% CI: 10.0–17.3), and mo (95% CI: 11.8–NR), and HR was 0.50 (95% CI, 0.36–0.70;
HR P<0.001) vs docetaxel
was 0.61 (95% CI, 0.49–0.75; P<0.001) vs docetaxel
aIn intent-to-treat population. At the cutoff date of September 30, 2015, median follow-up was 13.1 months.1
CI = confidence interval; HR = hazard ratio; NR = not reached; mo = months; OS = overall survival; PD-L1 = programmed death ligand 1; Q3W = every 3 weeks; TPS = tumor proportion score.
Graphs adapted from Herbst RS et al. Lancet. 2016;387(10027):1540–1550. Reprinted with permission from Elsevier.
1. Herbst RS et al. Lancet. 2016;387(10027):1540–1550. 2.Keytruda Lebanon Summary of Product Characteristics July 2017
 KEYTRUDATM (pembrolizumab):
Overall Summary and Conclusions: KEYNOTE-010
• Superior OS vs docetaxel in patients with previously treated advanced
NSCLC with positive PD-L1 expression (TPS ≥1)1
– 1-year estimated OS rate of 43% with KEYTRUDA 2 mg/kg Q3W vs 35% with
docetaxel

• Higher OS associated with higher levels of PD-L1 expression

(TPS ≥50%)1
• PFS was not significant for KEYTRUDA 2 mg/kg Q3W vs docetaxel in
patients with TPS ≥1% but was significant vs docetaxel in patients with
TPS ≥50%.1
• Most of the common AEs in KEYNOTE-010 were Grade 1 or 2.
– The most common AEs for KEYTRUDA 2 mg/kg Q3W occurring in ≥10% of patients
in any
group were decreased appetite, fatigue, and nausea.1
– The most common immune-mediated AEs for KEYTRUDA 2 mg/kg Q3W
were hypothyroidism, pneumonitis, and hyperthyroidism.1

AE = adverse event; NSCLC = non–small cell lung cancer; OS = overall survival; PD-L1 = programmed death ligand 1; Q3W = every 3 weeks; PFS = progression-free
survival; TPS = tumor proportion score.

1. Herbst RS et al. Lancet. 2016;387(10027):1540–1550.

Keytruda:

Treatment Option in the Management

of Metastatic Urothelial Malignancies

1
 Bladder Cancer: Highly Incident and Prevalent
Worldwide

Global Cancer Incidence1 Global 5-year Cancer Prevalence1

(5.8%)
(13.0%)

(19.2%)
(35.3%)
(11.9%) (35.2%)

Bladder Cancer
(9.7%) (4.1%)
Bladder Cancer (10.9%)
(3.1%) Lung
(1.4%)
Breast
(3.2%) (7.8%) Colorectum (11.9%)
Prostate
Stomach (4.7%)
(3.8%) (6.8%)
(5.6%) Liver (4.8%) (2.0%)
Cervix uteri
Esophagus
Bladder
Other and unspecified

1. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Population fact sheet: World (both sexes).
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed February 2016.
 Bladder Cancer: 5th Most Common Solid Tumor in
the US

Common types of cancer Estimated new cases 2016 (US)1

Breast cancer (female) 246,660
Lung and bronchus cancer 224,390
Prostate cancer 180,890
Colon and rectum cancer 134,490
Bladder cancer 76,960
Melanoma of the skin 76,380
Non-Hodgkin lymphoma 72,580
Thyroid cancer 64,300
Kidney and renal pelvis cancer 62,700
Leukemia 60,140

1. National Cancer Institute. SEER stat fact sheets: bladder cancer. http://seer.cancer.gov/statfacts/html/urinb.html. Accessed February 2017.
 Bladder Cancer Is Associated With Significant
Cancer-related Mortality
An estimated 165,084 deaths due to bladder cancer occurred in 2012 worldwide1

Estimated age-standardized incidence and mortality rates: both sexes Mortality

Breast
1,589,925 (19.4%)
Prostate

Lung 2,788,798 (34.0%)

521,907 (6.4%)
Colorectum

Cervix uteri 693,933 (8.5%)

165,084 (2.0%)
Stomach 307,481 (3.7%)
400,169 (4.9%)
Liver 265,672 (3.2%) 723,073 (8.8%)

Corpus uteri 745,533 (9.1%)

Ovary

Oesophagus Lung Breast Colorectum

Bladder Prostate Stomach Liver

Cervix uteri Oesophagus Bladder
Non-Hodgkin lymphoma
Other and unspecified
Leukaemia

Kidney
Incidence
Pancreas Mortality

0 10 20 30 40 50
ASR (W) rate per 100,000
ASR = age-standardized rate.
1. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Population fact sheet: World (both sexes).
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed February 2016.
KEYNOTE - 52

KEYTRUDA for the treatment of patients with

locally advanced or metastatic urothelial carcinoma
who are not eligible for cisplatin-containing
chemotherapy.
 KN-052 Study Design

Patients (N=350)
• Advanced urothelial cancer
• No prior chemotherapy for
metastatic disease
• ECOG PS 0-2
• Ineligible for cisplatin based Primary endpoints
Pembrolizumab • ORR in all patients
on ≥1 of the following: 200 mg
‒ CrCl <60 mL/min • ORR in patients with
Q3W
‒ ECOG PS 2 PD-L1-positive Tu
‒ ≥ Grade 2 neuropathy or
hearing loss
‒ NYHA class III CHF

First 100 patients included in the planned interim analysis:

• Evaluate ORR
• Determine the PD-L1-high expression cut point
CHF = congestive heart failure; CrCl = creatinine clearance; ECOG PS = Eastern Cooperative Oncology Group performance status; NYHA = New York Heart Association; ORR = objective response rate; PD-L1 =
programmed death ligand 1; Q3W = every 3 weeks.
1. Balar A, et al. Presented at ESMO 2016; Abstract LBA32_PR.
 KEYNOTE-052: Baseline Characteristics
N=370 N=370
Characteristic n (%) Treatment n (%)
Age, median (range), years 74 (34-94)
Previous adjuvant/neoadjuvant 36 (10)
<65 years 68 (18) platinum-based chemotherapy
≥65 years 302 (82) Reason for cisplatin ineligibility
Male 286 (77) ECOG PS 2 120 (32)
ECOG performance status Renal dysfunction 182 (49)
0 80 (22)
1 133 (36) ECOG performance status 2 and renal 35 (10)
dysfunction
2 156 (42)
Other reasons 33 (9)
Primary tumor location
Upper tract (renal pelvis/ureter) 69 (19)
Lower tract (bladder/urethra) 300 (81)

Metastases location, n (%) 315 (85)

ECOG = Eastern Cooperative Oncology Group.

Lymph node only 51 (14) †1 patient had an ECOG performance status of 3.

‡Primary tumor location was unknown for 1 patient.

Visceral disease a
315 (85) §Metastases location was not reported for 4 patients.

║ Adjuvant platinum-based chemotherapy following radical cystectomy or neoadjuvant platinum-based chemotherapy with recurrence

>12 months from completion of therapy was allowed.

††Renal dysfunction was defined as creatinine clearance <60 mL/min.

‡‡Other reasons include New York Heart Association Class III heart failure, grade ≥2 peripheral neuropathy, and grade ≥2 hearing loss.
1. Powles T et al. Presented at EAU 2017. Poster 170 Data cutoff date: September 1, 2016
KN-052: Maximum Change From Baseline in Target Lesions

58% of patients had a reduction

in tumour size from baseline

1. Powles T et al. Presented at EAU 2017. Poster 170 Data cutoff date: September 1, 2016
KN-052 Duration of response

• Median time to
response:
2 months (range,
0.2–5 months)

• Median duration of
response (DoR):
NR (range, 9–NR
months)

• 83% of all
responses
ongoing

1. Powles T et al. Presented at EAU 2017. Poster 170 Data cutoff date: September 1, 2016
Median follow-up duration was 5 months (range, 0.1-17 months)
 Confirmed ORR per RECIST v1.1 by Central Imaging
Vendor Review Based on Combined Positive Score ≥10%

1. Powles T et al. Presented at EAU 2017. Poster 170 Data cutoff date: September 1, 2016
Best percentage change from baseline per RECIST v1.1 by
central imaging

72% of patients with CPS ≥10% and 71% of those with CPS ≥10% enrolled at least
4 months at data cutoff experienced a reduction in tumor size from baseline

1. Powles T et al. Presented at EAU 2017. Poster 170 Data cutoff date: September 1, 2016
Summary

First-line Pembrolizumab demonstrated clinically meaningful

antitumor activity in:

1. Cisplatin-ineligible patients with advanced urothelial cancer

24% of all patients and 27% of those enrolled at least 4 months before
data cut-off responded to treatment

2. The PD-L1 high cut point was determined to be CPS ≥10%.

Higher response rates were observed in these patients. ORR was 48%
for those with CPS≥10% enrolled at least 4 months before data cutoff
83% of responses were ongoing as of the data cutoff
No new safety signals for Pembrolizumab were identified
 KEYNOTE-045

Pembrolizumab as Second-Line Therapy for

Advanced Metastatic Urothelial Carcinoma

Bellmunt, Joaquim, Guru Sonpavde, Ronald De Wit, Toni K. Choueiri, Arlene Seifker-Radtke, Elizabeth R. Plimack, Nicole M.
Lewis et al. "KEYNOTE-045: randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for
previously treated metastatic urothelial cancer." J Clin Oncol 33 (2015).
 KEYNOTE-045: KEYTRUDA™ (pembrolizumab)
vs Chemotherapy Study Design1

Randomized, open-label, multicenter trial, phase 3, patients with

advanced urothelial cancer that recurred or progressed after platinum-
based chemotherapy to receive Pembrolizumab

Patient Key Eligibility

Criteria
Intravenous infusions Treatment continued
until disease
Key Eligibility Criteria of KEYTRUDA 200 mg
•Urothelial carcinoma of the
progression or
renal pelvis, ureter, bladder,
Q3W (n=270) unacceptable toxicity
or urethra
R or for up to 24
•Transitional cell
1:1 months
predominant
Paclitaxel 175 mg/m2 Q3W
•PD after 1-2 lines of OR
Patients on
platinum-based chemo or Docetaxel 75 mg/m2 Q3W chemotherapy who
recurrence within 12 mo of
perioperative platinum-based
OR experienced PD
Vinflunine 320 mg/m2 Q3W were offered
therapy
(N= 272)
•ECOG PS 0-2 KEYTRUDA
•Provision of tumor sample
for biomarker assessment

Key End Points

Primary: OS and PFS in total and PD-L1 CPS ≥10% populations
Secondary: ORR and DOR in total and PD-L1 CPS ≥10% populations; Safety in
total population

CPS =Combined proportion score.

1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of Pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for
previously treated metastatic urothelial cancer." J Clin Oncol 33 (2015).
 KEYNOTE-045: KEYTRUDA™ (pembrolizumab)
vs Chemotherapy OS (Primary End Point)1
• 27% reduction in the risk of death with
KEYTRUDATM vs chemotherapy (HR=0.73; 95%
CI, 0.59–0.91; P=0.002).
–Number of deaths observed in each arm:
155/270 (57%) with KEYTRUDA vs
179/272 (66%) with chemotherapy 1

• The median overall survival was 10.3 mo

(95% CI, 8.0 to 11.8) in the Pembrolizumab
group, as compared with 7.4 mo (95% CI,
6.1 to 8.3) in the chemotherapy group 1

• 44% 1-year estimated OS rate with

KEYTRUDA vs 31% with chemotherapy. 1
PD-1 = programmed death receptor-1.

Image from Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously
treated metastatic urothelial cancer." J Clin Oncol 33 (2015).
1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated
metastatic urothelial cancer." J Clin Oncol 33 (2015).
 KEYNOTE-045: KEYTRUDA™ (pembrolizumab)
vs Chemotherapy ORR (secondary End Point)1
• Superior ORR with KEYTRUDA 200 mg Q3W vs chemotherapy
(In the total population, the objective response rate was significantly higher in the
Pembrolizumab group (21.1%; 95% CI, 16.4 to 26.5) than in the chemotherapy group
(11.4%; 95% CI, 7.9 to 15.8) (P = 0.001)

Superior overall response rate vs chemotherapy in second line

21%

21%
(95% CI, 16–27) CI = confidence interval;
KEYTRUDA 200 mg Q3W HR = hazard ratio;

ORR WITH 7%
11%
KEYTRUDA CR (95% CI, 8–16)
Chemotherapy

3% CR
14% PR
8% PR

P=0.001
CR = complete response; PR = partial response.

1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of Pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated
metastatic urothelial cancer." J Clin Oncol 33 (2015).
 KEYNOTE-045: Time to Response & Duration of
Response

Image from Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously
treated metastatic urothelial cancer." J Clin Oncol 33 (2015).
1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated
metastatic urothelial cancer." J Clin Oncol 33 (2015).
 Duration of response with KEYTRUDA vs
chemotherapy

Duration of response with KEYTRUDA vs chemotherapy

At the time of data cutoff, 41 of 57 patients (72%) with a response in the Pembrolizumab
group and 11 of 31 (35%) with a response in the chemotherapy group continued to have a
response.

• 68% of patients responding to KEYTRUDA had a response duration of ≥12

months vs 35% of patients responding to chemotherapy based on Kaplan-
Meier estimates. 1
• Median DOR had not been reached with KEYTRUDA at the time of
analysis (range: 1.6+ to 15.6+ months).
• Median DOR with chemotherapy was 4.3 months at the time of analysis
(range: 1.4+ to 15.4+ months).
• The median follow-up time was 10.3 months.

1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of Pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated
metastatic urothelial cancer." J Clin Oncol 33 (2015).
 Keynote 045 Conclusion1-2

• Phase 3 trial stopped early.

SUPERIOR • 27% reduction in the risk of death with KEYTRUDA™ vs

OS chemotherapy (HR=0.73; 95% CI, 0.59–0.91; P=0.002) 1

• 10.3-month (95% CI, 8.0–11.8) median OS with KEYTRUDA
vs 7.4 months (95% CI, 6.1–8.3) with chemotherapy 1
• PFS: There was no statistically significant difference in PFS
with KEYTRUDA vs chemotherapy (HR=0.98; 95% CI, 0.81–1.19;
P=0.416).1
• 44% 1-year estimated OS rate with KEYTRUDA vs 31% with
chemotherapy. 1

SUPERIOR • 21% (95% CI, 16–27) ORR with KEYTRUDA vs 11%

(95% CI, 8–16)
ORR with chemotherapy (P=0.001) 1
At the time of data cut-off 72% of patients with response
in the Pembrolizumab arm, and 35% with a response in
the chemotherapy arm continued to have response1.
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial
carcinoma who have received platinum-containing chemotherapy. 2

Most of the immune-mediated adverse reactions were Grade 1 or 2

• Adverse reactions occurring in patients with locally advanced or mUC were generally similar to those
occurring in patients with melanoma or NSCLC.

Recommended dosing: 200-mg fixed dose administered as an intravenous infusion over 30

minutes Q3W until disease progression or unacceptable toxicity 2

For patients with locally advanced or mUC, PD-L1 testing is not needed prior to use of KEYTRUDA2.
1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of Pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated
metastatic urothelial cancer." J Clin Oncol 33 (2015).
2. Keytruda Lebanon Summary of Product Characteristics July 2017
 KEYTRUDA™ (pembrolizumab): in Patients with advanced urothelial
carcinoma that progresses after platinum-based chemo-therapy & have a
poor prognosis and limited treatment options.

• The KEYNOTE-045 study of KEYTRUDA vs chemotherapy in second-

line treatment of patients with mUC met its primary end point:
• KEYTRUDA was superior compared with
chemotherapy for both the primary end point (OS) & (PFS) and
secondary end point (ORR) & (DOR)1.

• Based on these results, Pembrolizumab resulted in significantly longer

overall survival — by approximately 3 months than the investigator’s
choice of paclitaxel, docetaxel, or vinflunine and was associated with a
higher rate of objective response and a lower rate of treatment-related
adverse events than chemotherapy as second-line therapy in patients
with advanced urothelial carcinoma that progressed during or after
platinum-based chemotherapy, regardless of tumor PD-L1 expression
status.
• mUC: Metastatic urothelial Carcinoma OS: Overall Survival

• PFS: Progression free Survival ORR: Overall Response Rate DOR: Duration of Response

1. Bellmunt, Joaquim, et al. "KEYNOTE-045: randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously
treated metastatic urothelial cancer." J Clin Oncol 33 (2015).
 HEAD and Neck

KEYTRUDATM (Pembrolizumab)

as a Treatment Option in the

Management of Head & Neck Cancers
Global Incidence of Head & Neck Cancers1

• Global Incidence and Mortality of HNC

600,000
• 513,104
500,000

400,000

300,000 • 284,555

173,224
200,000
• 91,110
100,000

0
Men Women

•Incidence •Mortality

Globally, men are nearly 3 times more likely to have HNC than women

• 1. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/old/factsheet.asp. Accessed July 7, 2015.
 Epidemiology HNC (Oral Cavity and Pharynx)
Location, Site, and 5-Year Survival1

HNC Stage at Diagnosis HNC by Primary Site

Larynx 29%
Metastatic
18%
Regional
47% Oral Cavity (Lip,
Tongue) 46%
Paranasal or
Other2%
Unknown
5%

Pharynx (Hy-
Localized popharynx
31% Oropharynx,
Nasopharynx)
22%

5-year Relative Survival

83%

62%

38%

Localized Regional Metastatic

• 1. National Cancer Institute. SEER Cancer Statistics Review. http://seer.cancer.gov/statfacts/html/oralcav.html. Accessed July 10, 2015.
 A Multidisciplinary Approach Is Key
to Management of HNC
• Tumor Board/ Conference
• “HNC is such a specific disease where
• Radiation
you need a multidisciplinary approach, • Speech and
even early on. I think only the large
Oncologist/ • Typically held weekly
Swallowing Specialist Radiologist • Forum for open discussion
centers will have a HNC tumor board.”
about individual patient
• (Med Onc KOL, US) management
• More common in tertiary
care setting than
community
– Community hospitals

Patient more likely to have

general tumor boards
• Nurse Practitioner rather than HNC-
specific
• Surgeona
• (H&N/ENT/
Maxillofacial/Dental) • Other potential members
of
• Plastic surgeon
tumor board
• Gastroenterologist
• Nutritionist
• Psychologist (esp. EU)
• Dentist
• Key management decision • Social Worker
makers are shown in red; this
changes according to disease site
and stage.
• Pathologist • Medical
Oncologist
• a
Surgeon is likely to be the first point of referral in tertiary care setting.
•ENT = ear, nose and throat; EU = European Union; H&N = head and neck; HNC = head and neck cancer; JPN = Japan;
KOL = key opinion leader; Med = medical; Onc = oncologist.
• Maxillofacial mentioned in EU and dental surgeons mentioned in JPN; both specialize in oral cavity surgery. Surgeon plays key role in managing HNC I
•n JPN where medical oncology is an emerging specialty.
 HNSCC Treatment Overview1

• • Locoregionally • Recurrent/
Early
Advanced Metastatic HNC

• Definitive CRT

•
• Surgery • CT
− Platinum + RT

1st Line
• RT − Cetuximab/RT • Platinum + 5-FU +/-
cetuximab
• Surgery + RT/CRT

• 2nd Line +
• CT (single agent)
• Taxane
• MTX
• Cetuximab

• Other CT

•
(single agent)

3rd Line
• Gemcitabine
• Capecitabine
• Vinorelbine

• CT = computed tomography; CRT = chemoradiotherapy; HNC = head and neck cancer; HNSCC = head and neck
squamous cell carcinoma; MTX = methotrexate;
R/M = recurrent and/or metastatic; RT = radiotherapy.
• 1. Adapted from Cohen. Presented at: New Horizons in Immuno-therapy for HNC, OR 2015.
 Clinical Trials Evaluating KEYTRUDATM
(pembrolizumab)

• KEYNOTE-0121: Safety and clinical activity of

Pembrolizumab for treatment of recurrent or
metastatic squamous cell carcinoma of the head
and neck: an open-label, multicenter, phase 1b
trial.

1-Seiwert, Tanguy Y., et al. "Safety and clinical activity of Pembrolizumab for
treatment of recurrent or metastatic squamous cell carcinoma of the head and
neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial." The lancet
oncology 17.7 (2016): 956-965
 KEYTRUDATM (pembrolizumab):
Indication and Usage1

KEYTRUDA is indicated for the treatment of patients

with recurrent or metastatic HNSCC
with disease progression on or after platinum-
containing chemotherapy.
This indication is approved under accelerated
approval based on tumor response rate and durability
of response.

1. Keytruda Summary of Product Characteristics Lebanon July 2017.

 Safety and clinical activity of Pembrolizumab for treatment
of recurrent or metastatic squamous cell carcinoma of the
head and neck (KEYNOTE-012): an open-label, multicenter,
phase 1b trial1
• This study was an open-label, multicenter, phase 1b trial of patients with recurrent or
metastatic squamous cell carcinoma of the head and neck.
• Patients received Pembrolizumab 10 mg/kg intravenously every 2 weeks. .

• Recurrent/ metastatic squamous

cell carcinoma of the head and neck
• PD-L1 TPS ≥1%
• Measurable disease (RECIST v1.1)
Treatment until
• ECOG performance status 0-1 KEYTRUDA
disease
• provision of tumor tissue for PD-L1 10 mg/kg
progression or
expression analyses, HPV status, every 2 weeks
(n=60)
unacceptable
and biomarker assessment. toxicity
• No active brain metastases
• No active autoimmune disease
• No ILD or pneumonitis requiring
systemic steroids

Response assessment: Every 8 weeks

Primary end points: ORR (RECIST v1.1, central imaging vendor), safety
Secondary end points: ORR (investigator), PFS, OS, response duration, ORR in HPV+ patients §
1. Seiwert, Tanguy Y., et al. "Safety and clinical activity of Pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an

open-label, multicentre, phase 1b trial." The lancet oncology 17.7 (2016): 956-965 .
 Results 1

• The proportion of patients with an overall response (confirmed per central imaging review)
was 18% (8 of 45;95% CI 8–32).

• Median time to response was 8 weeks (95% CI 7–17) and the median duration of response
was 53 weeks (13 to not reached).

• Median progression-free survival was 2 months (95% CI 2–4) in the full analysis set
population (n=56).

• Median overall survival was 13 months (95% CI 5 to not reached) in the ITT population
(n=61)

• Median OS was not reached for HPV-positive patients (8 to not reached), and 8 months (4
to not reached) for HPV-negative patients

• Patient survival at 12 months is 51%

1 Seiwert, Tanguy Y., et al. "Safety and clinical activity of Pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck
(KEYNOTE-012): an open-label, multicenter, phase 1b trial." The lancet oncology 17.7 (2016): 956-965.
 Results :Overall Survival (%) 1

• Median overall survival was 13 months (95% CI 5 to not reached) in the ITT population (n=61)
• Median overall survival was not reached for HPV-positive patients (8 to not reached), and 8 months (4
to not reached) for HPV-negative patients.
• Patient survival at 12 months is 51%
1 Table from Seiwert, Tanguy Y., et al.et al. The lancet oncology 17.7 (2016): 956-965.
1 Seiwert, Tanguy Y., et al. "Safety and clinical activity of Pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-
label, multicenter, phase 1b trial." The lancet oncology 17.7 (2016): 956-965.
ITT: Intent to Treat
 Conclusion1

In summary, Pembrolizumab showed clinically significant activity in patients with heavily

pretreated squamous cell carcinoma of the head and neck irrespective of HPV status.

Thus Pembrolizumab might represent a new treatment approach for patients with squamous
cell carcinoma of the head and neck.

1. Seiwert, Tanguy Y., et al. "Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label,
multicentre, phase 1b trial." The lancet oncology 17.7 (2016): 956-965
PEMBROLIZUMAB IN
METASTATIC MELANOMA
 KEYNOTE-002

7
Pembrolizumab Versus Ipilimumab in Patients With Ipilimumab-
Naive Advanced Melanoma: Updated Efficacy and Safety of the
Phase 3 KEYNOTE-006 Study

Jacob Schachter, 1 Caroline Robert, 2 Georgina V. Long, 3 Ana Arance, 4 Jean-Jacques Grob, 5 Laurent Mortier, 6 Adil Daud, 7 Matteo S. Carlino, 8 Catriona
McNeil, 9 Michal Lotem, 10 James Larkin, 11 Paul Lorigan, 12 Bart Neyns, 13 Christian U. Blank, 14 Omid Hamid, 15 Shailender Bhatia, 16 Honghong Zhou, 17 Scot
Ebbinghaus, 17 Nageatte Ibrahim, 17 Antoni Ribas 18
1
Ella Lemelbaum Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel; 2Gustave Roussy, Villejuif, France, and Université Paris-Sud, Paris-
Sud, France; 3Melanoma Institute Australia, The University of Sydney, and Mater Hospital, Sydney, Australia; 4Hospital Clinic and Translational Genomics
and Targeted Therapeutics in Solid Tumors (IDIBAPS), Barcelona, Spain; 5Hôpital de la Timone, Marseille, France; 6Université Lille, CHRU LILLE, Lille,
France; 7University of California, San Francisco, San Francisco, CA, USA; 8Westmead and Blacktown Hospitals, The University of Sydney, and Melanoma
Institute Australia, Sydney, Australia; 9Chris O’Brien Lifehouse, Royal Prince Alfred Hospital, and Melanoma Institute Australia, Camperdown, Australia;
10
Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel; 11 The Royal Marsden Hospital, London, UK; 12 University of
Manchester and The Christie NHS Foundation Trust, Manchester, UK; 13 Universitair Ziekenhuis Brussel, Brussels, Belgium; 14 The Netherlands Cancer
Institute, Amsterdam, Netherlands; 15 The Angeles Clinic and Research Institute, Los Angeles, CA, USA; 16 University of Washington, Seattle, WA, USA;
17
Merck & Co., Inc., Kenilworth, NJ, USA; 18 University of California, Los Angeles, Los Angeles, CA, USA

Presented at the Society for Melanoma Research 2015 Congress;

November 18-21, 2015; San Francisco, California, USA
Study Design
Progression-Free Survival

With 6 months of additional follow-up, pembrolizumab continued to provide superior

PFS compared with ipilimumab ( P < 0.0001), with no difference in PFS between
pembrolizumab schedules
Progression-Free Survival (RECIST v1.1, central review)
Tumor Response (RECIST v1.1, central review)
 Conclusions

At IA2, pembrolizumab demonstrated superior OS over ipilimumab 1 and, as

reported here, continued to demonstrate superior PFS and ORR over
ipilimumab, with no difference between pembrolizumab schedules
Responses continued to be durable in all treatment arms
The incidence of grade 3-5 treatment-related AEs remained lower for
pembrolizumab compared with ipilimumab, despite the longer treatment
duration for pembrolizumab
Results support pembrolizumab as a new standard of care in patients with
advanced melanoma not previously treated with ipilimumab

1. Robert C et al. N Engl J Med. 2015;372:2521-2532.

 KEYTRUDATM (Pembrolizumab)

as a Treatment Option in the Management

of Classical Hodgkin lymphoma
 Hodgkin Disease: Epidemiology

• Epidemiology in the US1,2

– In 2014, ~9,190 people will be
diagnosed with HD1
– 10% to 15% of cases in children and teenagers2 HD: New Cases/Year
• Approximately 1,180 deaths/year1 6,000
5,070
– Females: 5101 5,000

New Diagnoses
4,120
4,000
– Males: 670 1
3,000
• Survival rates2
2,000
– 1 year: 92%2
1,000
– 5 years: 85%2 0
Males Females
– 10 years: 80%2

1. Siegel R et al. CA Cancer J Clin. 2014;64(1):9-29. 2. American Cancer Society. What are the key statistics of HD? http://www.cancer.org/cancer/hodgkindisease/detailedguide/hodgkin-
disease-key-statistics. Accessed September 29, 2014.
 5-Year Relative Survival1

100 Survival by Stage at Diagnosis

90.8 92.1
90
80.7
80 76.2
70
Percent (%)

60
50
40
30
20
10
0
Localized Regional Distant Unstaged
1.National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER) stat fact sheets: Hodgkin disease.
http://seer.cancer.gov/statfacts/html/hodg.html. Accessed September 30, 2014.
 Clinical Trials Evaluating
KEYTRUDATM (Pembrolizumab)

Phase II Study of the Efficacy and Safety of

Pembrolizumab for Relapsed/Refractory Classic
Hodgkin Lymphoma: Keynote 087
Robert Chen, Pier Luigi Zinzani, Michelle A. Fanale, Philippe Armand,
Nathalie A. Johnson, Pauline Brice, John
Radford, Vincent Ribrag, Daniel Molin, Theodoros P. Vassilakopoulos,
Akihiro Tomita, Bastian von Tresckow,
Margaret A. Shipp, Yinghua Zhang, Alejandro D. Ricart, Arun Balakumaran,
Craig H. Moskowitz, for the
KEYNOTE-087 Investigators
 KEYNOTE-087 Study design1

• KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) is a multicenter, single-arm

phase II study of Pembrolizumab in three cohorts of patients with rrHL.

• Cohorts were defined based on lymphoma progression after (1) ASCT and subsequent
BV; (2) salvage chemotherapy and BV, and thus ineligible for ASCT because of chemo-
resistant disease; and (3) ASCT but had not received BV after transplantation.

Patients in cohort could have received BV as part of primary treatment or as salvage

treatment or could have been BV naïve.

1. Chen, Robert W., et al. "Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study." (2016): 7555-7555.
 Efficacy1

Table from 1. Chen, Robert W., et al. "Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study." (2016): 7555-7555.
1. Chen, Robert W., et al. "Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study." (2016): 7555-7555.
 Efficacy1

• At 6 months, the OS rate was 99.5%, and the PFS rate was 72.4%.

• Thirty-one patients (75.6%) had a response ≥ 6 months.

• Median OS was not reached, with only four deaths occurring.

• the 9-month OS and PFS rates were 97.5% and 63.4%, respectively.

1. Chen, Robert W., et al. "Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study." (2016): 7555-7555.
 Conclusions1

• Pembrolizumab monotherapy demonstrates a high level of clinically relevant anti-tumor

activity in subjects with rrcHL including the achievement of a complete response in more

than one fifth of subjects

• The ORR, including CR, observed with pembrolizumab in heavily pretreated subjects is

clinically meaningful

• The duration of response has not been reached in this study, with a range of 0.0+ to 8.3

months

• These results demonstrate consistent and clinically meaningful activity of pembrolizumab

200mg Q3W in heavily pretreated subjects with rrcHL

1. Chen, Robert W., et al. "Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study." (2016): 7555-7555.
 KEYTRUDATM (Pembrolizumab): Indication and
Usage1

Keytruda is indicated for the treatment of adult and pediatric patients with refractory
cHL, or who have relapsed after 3 or more prior lines of therapy.
This indication is approved under accelerated approval based on
tumor response rate and durability of response.
Continued approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials.

1. Keytruda Lebanon Summary of Product Characteristics July 2017

Keytruda Highlights
Non-Small Cell Lung Cancer

First Line Combination Key-021G

{Keytruda+Carbo+Pem} vs {Carbo+Pem}
PFS: 13mo vs 8.9mo HR: 0.53
ORR: 55% vs 29%
OS: NR
DOR: NR

First Line Monotherapy Key-024

Keytruda vs Chemotherapy
PFS: 10.3mo vs 6mo HR: 0.5
OS: NR HR: 0.6
ORR: 45% vs 28%
Around 47% of chemo patients crossed over to Pembro Arm

Second Line Monotherapy Key-010

Keytruda Vs Docetaxel
OS: 10.4mo vs 8.2mo HR:0.7
ORR: 18% vs 9%
Metastatic Urothelial Carcinoma

First Line Cisplatin Ineligible Patient Key-052

Single arm Phase 2 trial
ORR Total Population: 24%
ORR after 4 month on keyrtuda: 27%
58% of patients had a reduction in tumour size from baselin
Second Line Key-045
Keytruda vs Chemotherapy
OS: 10.3mo vs 7.4mo HR:0.73
ORR: 21.7%
CR: 7%
Head and Neck

Second Line for treatment of recurrent or metastatic squamous cell carcinoma of the head and
neck:Key-012

The proportion of patients with an overall response (confirmed per central imaging review)
was 18% (8 of 45;95% CI 8–32).

Median time to response was 8 weeks (95% CI 7–17) and the median duration of response
was 53 weeks (13 to not reached).

Median progression-free survival was 2 months (95% CI 2–4) in the full analysis set
population (n=56).

Median overall survival was 13 months (95% CI 5 to not reached) in the ITT population (n=61)

Median OS was not reached for HPV-positive patients (8 to not reached), and 8 months (4 to
not reached) for HPV-negative patients

Patient survival at 12 months is 51%

Metastatic Melanoma

1st line Monotherapy : Keynote 006

OS: 55% vs 43% ipilimumab (at 2 years)
ORR: 36% vs 12% ipilimumab
PFS: 38% vs 17% ipilimumab (at 1 year)

2nd line Monotherapy : Keynote 002:

PFS: 22% vs 0.6% chemo (at 2 years)
ORR: 28% vs 4% chemo
OS: 38% vs 27% chemo (at 2 years)
cHL

3rd line and above for Relapsed/Refractory Classic Hodgkin Lymphoma: Key-087
ORR: 70%
CR: 22%
Only drug approved for pediatric use (2mg/kg dose q3 weeks up to
maximum of 200mg q3 weeks)
THANK YOU