1. KEYNOTE-012: Durable Efficacy With Pembrolizumab in PD-L1–Positive Gastric Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*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.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. KEYNOTE-012: Gastric Cancer Cohort Study Design
Multicenter, multicohort open-label phase Ib trial
Endpoints: Association of clinical response with PD-L1 expression
Assessment of response every 8 wks by RECIST v.1
Assessment of PD-L1 expression by immunohistochemistry
Discontinue treatment
Pts with PD-L1–positive recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction; ECOG PS 0-1; no active brain metastases
(N = 39) CR
Pembrolizumab
10 mg/kg IV q2w
PR, SD
Pembrolizumab 10 mg/kg IV q2w for 24 mos or until progression or intolerable toxicity
Confirmed
progressive
disease
Discontinue treatment
CR, complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; IV, intravenous; PR, partial response; q2w, every 2 weeks; RECIST, response evaluation criteria in solid tumors; SD, stable disease.
Bang YJ, et al. ASCO Abstract 4001.

3. KEYNOTE-012: Baseline Characteristics
Pt Characteristics: Gastric Cancer Cohort (N = 39)
Male, n (%)
28 (72)
Median age, yrs (range)
63 (33-78)
Race, n (%)
White
Asian
19 (49)
ECOG PS, n (%) 1
17 (44)
22 (56)
Prior gastrectomy, n (%)
20 (51)
No. of prior therapies for advanced disease, n (%)
≤ 1
≥ 2
Unknown
9 (23)
26 (67)
4 (10)
ECOG PS, Eastern Cooperative Oncology group performance status.
Bang YJ, et al. ASCO Abstract Reprinted with permission.

4. KEYNOTE-012: Response
Pembrolizumab therapy associated with PR in 13 of 39 pts by investigator review and 8 of 36 pts by central review
53% of pts had decrease in lesion size
Median time to response: 8 wks
4 of 8 responses ongoing at time of data cutoff
Median response duration: 40 wks (range: 20+ to 48+)
Outcomes
Response
Investigator Review
(n = 39)
Central Review
(n = 36)
ORR, % (95% CI)
33 (19-50)
22 (10-39)
Best response, n (%) CR PR
13 (33)
8 (22) SD
3 (8)
5 (14) PD
23 (59)
19 (53)
No assessment
1 (3)
Not determined
CR, complete response; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Bang YJ, et al. ASCO Abstract Reprinted with permission.

5. KEYNOTE-012: PFS and OS 6-mo PFS rate: 26%
100
100 90 90 80 80 70 70 60 60
PFS (%) 50
OS (%) 50 40 40 30 30 20 20 10 10 2 4 6 8 10 12 14 2 4 6 8 10 12 14 16
NR, not reached; OS, overall survival; PFS, progression-free survival.
Mos
Mos
Pts at Risk, n
Pts at Risk, n 36 14 12 9 7 5 1 36 31 25 22 18 15 7 5
6-mo PFS rate: 26%
Median PFS: 1.9 mos (95% CI: )
6-mo OS rate: 66%
Median OS: 11.4 mos (95% CI: 5.7-NR)
Bang YJ, et al. ASCO Abstract Reprinted with permission.

6. PD-L1 Expression as Continuous Variable vs Efficacy
KEYNOTE-012: Association Between PD-L1 Expression and Clinical Response
Association noted between PD-L1 expression and efficacy in this small sample
PD-L1 expression was assessed using IHC assay using 22C3 antibody
Both PD-L1 positive tumor cells and PD-L1 positive immune cells were identified
Data suggest low cutoff sufficient to detect most responders
PD-L1 Expression as Continuous Variable vs Efficacy
One-Sided P Value
Central review (N = 35)
ORR
PFS
.082
.269
Investigator review (N = 38)
.120
.237
OS (N = 38)
.010
ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
Bang YJ, et al. ASCO Abstract Reprinted with permission.

7. KEYNOTE-012: Treatment Exposure and Response Duration
Median response duration: 40 wks (range: 20-48)
Median time to response: 8 wks
4 of 8 responses ongoing at time of data cutoff (March 23, 2015)
Partial response Progressive disease
Progressive disease after non-progressive disease
Last pembrolizumbab dose
Pembrolizumab treatment ongoing 8 16 24 32 40 48 56 64
Time, weeks
Patients with measurable disease per RECIST v1.1 by central review at baseline who had ≥ postbaseline assessment (n=35).
Bang YJ, et al. ASCO Abstract Reprinted with permission.

8. KEYNOTE-012: Treatment-Related AEs
Few pts with AEs grade ≥ 3
Toxicity mainly as previously seen with pembrolizumab
No treatment-related deaths
Colitis, hepatitis, autoimmune thyroiditis in 1 pt each
All grade 1 or 2
2 pts discontinued therapy
Hypothyroidism, n = 1
Pneumonitis, n = 1
Pembrolizumab-Associated AE (N = 39), n (%)
Any toxicity
Grade 3/4
26 (67)
5 (13)
Fatigue, any
Grade 3
7 (18)
2 (5)
Hypothyroidism, any
1 (3)
Pruritus
Arthralgia
4 (10)
Hyperthyroidism
3 (8)
Nausea
Peripheral neuropathy, any
Grade 3 pemphigoid
Grade 4 pneumonitis
AE, adverse event.
Bang YJ, et al. ASCO Abstract Reprinted with permission.

9. KEYNOTE-012: Investigator Conclusions
Pembrolizumab shows durable efficacy in treatment-experienced pts with advanced PD-L1–positive gastric cancer
In this preselected pt population, association noted between PD-L1 expression and efficacy
ORR: 22% (central review)
Median duration of response: 40 wks
Median OS: 11 mos
Safety and efficacy similar with pembrolizumab in other tumor types
Manageable toxicity with no new events observed
Other phase I and II trials ongoing in pts with advanced gastric cancer
ORR, overall response rate; OS, overall survival.
Bang YJ, et al. ASCO Abstract 4001.

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