Prior results from the global, phase 2 KEYNOTE-059 study (NCT02335411) demonstrated manageable safety and promising antitumor activity for pembro alone and pembro + chemo in pts with G/GEJ cancer.
Pts with recurrent or metastatic G/GEJ adenocarcinoma were enrolled. Pts were enrolled in cohorts 1 and 2 regardless of tumor PD-L1 expression; only pts with PD-L1-positive tumors (combined positive score of ≥ 1% using the PD-L1 IHC 22C3 pharmDx assay) were enrolled in cohort 3. Cohort 1 pts received pembro alone after ≥2 prior lines of therapy. Cohort 2 pts received pembro + cisplatin (80 mg/m2 day 1) + 5-fluorouracil (800 mg/m2 days 1-5 Q3W) or capecitabine (in Japan only, 1000 mg/m2 twice daily) as first-line. Cohort 3 pts received pembro alone as first-line. In all cohorts, pembro was given at 200 mg Q3W for up to 2 years. Primary end points were safety (all) and ORR by RECIST v1.1 by central review (cohorts 1 and 3); key secondary end points were ORR (cohort 2) and DOR by RECIST v1.1, PFS, and OS.
At data cutoff (Apr 21, 2017), median (range) follow-up was 6 (1-25), 14 (2-24), and 18 (2-21) months for cohorts 1 (259 pts), 2 (25 pts) and 3 (31 pts), respectively. Confirmed ORR (95% CI) was 12% (8-17) overall, 16% (11-23) in PD-L1-positive, and 6% (3-13) in PD-L1-negative tumors in cohort 1. Confirmed ORR was 60% (39-79) overall, 73% (45-92) in PD-L1-positive, and 38% (9-76) in PD-L1-negative tumors in cohort 2. In cohort 3, confirmed ORR (95% CI) was 26% (12-45). Median PFS (95% CI) was 2 (2-2), 7 (6-11), and 3 (2-6) months in cohorts 1, 2, and 3, respectively. Median OS (95% CI) in months was 6 (4-7), 14 (9-not estimable), and not reached (9-21) in cohorts 1, 2, and 3, respectively. In cohorts 1, 2 and 3, grade 3-5 treatment-related adverse event (TRAE) incidence was 46 (18%), 19 (76%), and 7 (23%), respectively. In cohort 1, TRAEs led to discontinuation in 7 pts (3%) and death in 2 pts (1%); in cohort 2, TRAEs led to discontinuation in 3 pts (12%); in cohort 3, TRAEs led to death in 1 pt (3%).
These updated results show manageable safety and promising antitumor activity for pembro alone and pembro + chemo in pts with advanced G/GEJ cancer.
Clinical trial identification
Legal entity responsible for the study
Merck & Co, Inc.
Merck & Co, Inc.
Z.A. Wainberg: Consultant for Genetech, Array, Sirtex, Novartis, and Five Prime Therapeutics. S. Jalal: Research funding: AstraZeneca. K. Muro: Research funding: Shionogi & Co, MSD K.K., Daiichi Sankyo, Kyowa Hakko Kirin,. Gilead Sciences Honoraria: Chugai Pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan K.K., Merck Serono, Taiho, Yakult Honsha. T. Doi: Advisory board: Lilly, Chugai Pharma, Kyowa Hakko, Kirin, Novartis, MSD, Daiichi Sankyo, Amgen Research funding: Taiho, Novartis, Merck Serono, Astellas, MSD, Janssen Pharma, Behringer Ingelheim, Takeda, Pfizer, Lilly, Sumitomo Group, Chugai Pharma, Bayer, Kyowa Hakko, Kirin, Daiichi Sankyo, Celegene. D.V. Catenacci: Advisory board: Merck, BMS, Lilly, Genentech Honoraria: Merck, BMS, Lilly, Genentech Travel expenses, including accommodations: Merck, BMS, Lilly, Genentech. R. Geva: Advisory board: Bayer, MSD, Novartis Honoraria: BMS, Lilly, Medison, Roche, Novartis, Janssen Travel expenses: Roche, BMS. G. Ku: Advisory board member: Merck Research funding: Merck (to institution) Travel expenses: Merck J. Bleeker: Travel expenses: Merck & Co., Inc. Consultant fee: BMS. Y-J. Bang: Advisory board: AstraZeneca, Novartis, Roche, Genentech, MSD, Pfizer, Bayer, BMS, Eli Lilly, Merck Serano, FivePrime, Merrimack, Taiho, Ono, ADC Therapeutics, GreenCross, Samyang Biopharm Research funding: AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serano, Bayer, GSK, BMS, Pfizer, Eli Lilly, Boeringer-Ingelheim, MacroGenics, Boston Biomedical, FivePrime, CKD, Ono, Otsuka, Taiho, Takeda, BeiGene, Hanmi, Green Cross, Curis. H. Hara: Research funding to institution: AstraZenaca, Chugai Pharma, Merck Serono, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Boehringer Ingelheim, Dainippon Sumitomo Pharma, Daiichi Sankyo, Lilly Honoraria: Chugai Pharma, Taiho Pharmaceuticals, Merck Serono, Yakult Honsha, Lilly. M. Savage, J. Wang, M. Koshiji, R. Dalal: Employment: Merck & Co., Inc. C.S. Fuchs: Advisory board: Eli Lilly, Entrinsic Health, Genentech, Merck, Gilead, Sanofi, Dicerna, Five Prime Therapeutics, Merrimack, Bayer, Agios, Taiho. All other authors have declared no conflicts of interest.