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.

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 2015. Abstract 4001.

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 2015. Abstract 4001. Reprinted with permission.

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 2015. Abstract 4001. Reprinted with permission.

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: 1.8-3.5) 6-mo OS rate: 66% Median OS: 11.4 mos (95% CI: 5.7-NR) Bang YJ, et al. ASCO 2015. Abstract 4001. Reprinted with permission.

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 2015. Abstract 4001. Reprinted with permission.

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 2015. Abstract 4001. Reprinted with permission.

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 2015. Abstract 4001. Reprinted with permission.

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 2015. Abstract 4001.

Go Online for More CCO Coverage of ASCO 2015! Short slidesets of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in: Gastrointestinal cancers Lung cancer Hematological malignancies Immunotherapy Genitourinary cancer clinicaloptions.com/oncology