1. KEYNOTE-059 (Cohort 1): Pembrolizumab Monotherapy in Previously Treated Advanced Gastric or GEJ Adenocarcinoma
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
GEJ, gastroesophageal junction.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Pembrolizumab for Pretreated Advanced Gastric or GEJ Adenocarcinoma: Background
PD-L1 overexpression a feature of gastric cancers[1-3]
Pembrolizumab: humanized anti–PD-1 IgG4-κ mAb; blocks PD-1 interaction with its ligands PD-L1/2[4]
Phase Ib KEYNOTE-012: manageable toxicity, 22% ORR in pts with advanced PD-L1+ gastric cancer[5]
Current analysis reports data from phase II KEYNOTE-059 of pembrolizumab with focus on cohort 1 (pts with advanced gastric/GEJ cancer and ≥ 2 prior lines of therapy who received pembrolizumab monotherapy)[6]
GEJ, gastroesophageal junction.
1. Kim JW, et al. Gastric Cancer. 2016;19: Qing Y, et al. Drug Des Devel Ther. 2015;9:
3. Dong M, et al. Hum Pathol. 2016;53: Pembrolizumab [package insert]. 5. Muro K, et al. Lancet Oncol. 2016;17: Fuchs CS, et al. ASCO Abstract 4003.
Slide credit: clinicaloptions.com

3. KEYNOTE-059: Study Design
Open-label, multicohort phase II study
Primary endpoints: ORR, safety; secondary endpoints: DoR, PFS, OS
Exploratory biomarker endpoints: efficacy by MSI, GEP
Cohort 1
≥ 2 prior lines of CT
Pembrolizumab
200 mg Q3W
Pts with recurrent or metastatic gastric or GEJ adenocarcinoma; ECOG PS 0/1; HER2/neu negative*; no prior PD-1/PD-L1 tx, systemic steroids, autoimmune disease, ascites, or CNS mets
(N = 259)
Tx continued for 24 mos or until PD, intolerable toxicity, or withdrawal of consent; survival follow-up until study end, death, or withdrawal
Pembrolizumab 200 mg Q3W +
Cisplatin 80 mg/m2 Q3W +
5-FU 800 mg/m2 Q3W or
Capecitabine 1000 mg/m2 BID Q3W
Cohort 2
No prior tx
Cohort 3
No prior tx, PD-L1+
Pembrolizumab
200 mg Q3W
5-FU, 5-fluorouracil; CNS, central nervous system; CT, chemotherapy; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; GEJ, gastroesophageal junction; mets, metastases; GEP, gene expression profile; MSI, microsatellite instability; PD, progressive disease; PS, performance status; tx, treatment.
*HER2/neu positive allowed in cohort 1 if prior trastuzumab administered.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract 4003.

4. KEYNOTE-059 (Cohort 1): Baseline Characteristics
All Pts
(N = 259)
Median age, yrs (range)
62 (24-89)
Male, n (%)
198 (76.4)
Geographic region, n (%)
United States
East Asia
Other
124 (47.9)
34 (13.1)
101 (39.0)
ECOG PS, n (%) 1
107 (41.3)
151 (58.3)
Primary tumor location, n (%)
Gastric
GEJ
125 (48.3)
133 (51.4)
Characteristic, n (%)
All Pts
(N = 259)
Prior therapies 2 3
≥ 4
134 (51.7)
75 (29.0)
50 (19.3)
Prior surgery for gastric cancer
66 (25.5)
HER2 positive
63 (24.3)
PD-L1 expression
Positive*
Negative
148 (57.1)
109 (42.1)
CPS, combined positive score; ECOG, Eastern Cooperative Oncology Group; GEJ, gastroesophageal junction; PS, performance status.
*CPS ≥ 1% where CPS is (PD-L1 staining cells/total tumor cells) x 100.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract 4003.

5. KEYNOTE-059 (Cohort 1): Response
Median follow-up: 5.8 mos (range: mos)
Confirmed Response, % (95% CI)
All Pts (N = 259)
ORR
11.6 ( ) CR
2.3 ( ) PR
9.3 ( ) SD
16.2 ( ) PD
56.0 ( )
DCR*
27.0 ( )
DCR, disease control rate; PD, progressive disease; SD, stable disease.
*CR + PR + SD ≥ 2 mos.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract 4003.

6. KEYNOTE-059 (Cohort 1): Safety
TRAE Occurring in > 5% of Pts, %
All Pts (N = 259)
Any Grade
Grade 3/4
Fatigue
18.9
2.3
Pruritus
8.9
Rash
8.5
0.8
Hypothyroidism
7.7
0.4
Decreased appetite
7.3
Anemia
6.9
2.7
Nausea
Diarrhea
6.6
1.2
Arthralgia
5.8
irAE Occurring in > 1% of Pts, %
All Pts (N = 259)
Any Grade
Grade 3/4
Any
17.8
4.6
Hypothyroidism
8.9
0.4
Hyperthyroidism
3.5
Colitis
2.3
1.2
Pneumonitis
1.9
0.8
Thyroiditis
1.5
Infusion reaction
Severe skin reaction*
D/c, discontinued; irAE, immune-related adverse event; TRAE, treatment-related adverse event.
*Includes erythema multiforme, jaundice, rash, maculopapular rash.
Systemic corticosteroids for irAEs: n = 13.
Treatment interruption due to irAEs: n = 10.
D/c for TRAEs: abnormal hepatic function, bile duct stenosis, n = 1 each.
Grade 5 TRAEs: acute kidney injury, pleural effusion, n = 1 each.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract 4003.

7. PD-L1 and Third Line of Therapy
KEYNOTE-059 (Cohort 1): Response by PD-L1 Expression and Line of Therapy
Confirmed Response, % (95% CI)
PD-L1
Line of Therapy
PD-L1 and Third Line of Therapy
Positive
(n = 148)
Negative
(n = 109)
Third
(n = 134)
≥ Fourth
(n = 125)
(n = 75)
(n = 58)
ORR
15.5
( )
6.4
( )
16.4
( )
( )
22.7
( )
8.6
( ) CR
2.0
( )
2.8
( )
3.0
( )
1.6
( )
2.7
( )
3.4
( ) PR
13.5
( )
3.7
( )
13.4
( )
4.8
( )
20.0
( )
5.2
( )
DCR*
33.1
( )
19.3
( )
31.3
( )
22.4
( )
38.7
( )
( )
DCR, disease control rate; SD, stable disease.
*CR + PR + SD ≥ 2 mos.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract 4003.

8. KEYNOTE-059 (Cohort 1): Maximum Change From Baseline in Target Lesion Size
120
PD-L1 positive
PD-L1 negative
PD-L1 expression unknown
Pts With Reduction, %
All pts*
42.4
PD-L1 positive
47.3
PD-L1 negative
36.3
100 80 60
*Included pts with measurable disease at BL and ≥ 1 post-BL assessment (n = 223). 40 20
Change From BL (%)
-20
BL, baseline
-40
-60
-80
-100
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract Reproduced with permission.

9. KEYNOTE-059 (Cohort 1): Depth and Duration of Response
Treatment Exposure and Duration of Response
Longitudinal Change From BL in Tumor Size Among Responders (n = 30) 20
Treatment discontinued
Treatment ongoing
-20
Change From BL (%)
Confirmed Responders (n = 30)
-40
CR PR PD
Death
Ongoing pembrolizumab treatment
-60
-80
BL, baseline; DoR, duration of response; PD, progressive disease.
-100 2 4 6 8 10 12 14 16 18 20 22 24 2 4 6 8 10 12 14 16 18 20 22 24
Mos Since First Dose
Mos Since Treatment Initiation
Outcome
All Pts*
PD-L1+
PD-L1-
Median DoR, mos (95% CI)
8.4 (1.6+† to 17.3+)
16.3 (1.6+ to 17.3+)
6.9 (2.4 to 7.0+)
*Included pts with measurable disease at BL and ≥ 1 post-BL assessment (n = 30). †No PD at last disease assessment.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract Reproduced with permission.

10. KEYNOTE-059 (Cohort 1): SurvivalOS
PFS
All Pts (N = 259)
Median OS, mos (95% CI)
5.6 ( )
12-mo OS rate, %
23.4
All Pts
(N = 259)
Median PFS, mos (95% CI)
2.0 ( )
100
100 80 80 60 60
OS (%)
PFS (%) 40 40 20 20 2 4 6 8 10 12 14 16 18 20 22 2 4 6 8 10 12 14 16 18 20 22
Mos
Mos
Pts at risk, n
Pts at risk, n
259
199
144
112 87 51 27 22 12 7 2
259
136 51 34 22 17 4 2 2 2
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract Reproduced with permission.

11. KEYNOTE-059 (Cohort 1): Exploratory Analyses
Confirmed Response, % (95% CI)
MSI-High
(n = 7)
Non–MSI-High
(n = 167)
ORR
57.1
( )
9.0
( ) CR
14.3 ( )
2.4 ( ) PR
42.9 ( )
6.6 ( )
DCR*
71.4 ( )
22.2 ( )
0.5
0.0
18-Gene T-Cell−Inflamed GEP Score
-0.5
Nonresponder
Responder
*CR + PR + SD ≥ 2 mos.
DCR, disease control rate; GEP, gene expression profile; MSI, microsatellite instability; SD, stable disease.
MSI assessed in 174 pts
MSI-high: 4.0%
18-gene T-cell–inflamed GEP score, assessed in 144 pts, associated with significantly improved response to pembrolizumab (P = .014)
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract Reproduced with permission.

12. KEYNOTE-059 (Cohort 1): Conclusions
In pts with advanced gastric/GEJ cancer and ≥ 2 prior therapies, pembrolizumab well tolerated with promising antitumor activity, durable responses
ORR: 11.6%; higher in PD-L1+ vs PD-L1- tumors (15.5% vs 6.4%) and MSI-high vs non–MSI-high tumors (57.1% vs 9.0%)
Study investigators suggest pembrolizumab as potential therapeutic option for this pt population
Pembrolizumab in earlier-line therapy and in chemotherapy combinations under investigation for advanced gastric/GEJ cancer in ongoing randomized trials
GEJ, gastroesophageal junction; MSI, microsatellite instability.
Slide credit: clinicaloptions.com
Fuchs CS, et al. ASCO Abstract 4003.

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