Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)
Summary
The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in combination with chemotherapy (Cisplatin combined with 5-Fluorouracil \[FP regimen\] or oxaliplatin combined with capecitabine \[CAPOX regimen\]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of human epidermal growth factor receptor 2 (HER2) negative advanced gastric or GEJ adenocarcinoma in adult participants. The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS). Once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and enrolled in an extension study (Keynote 587; NCT03486873) to continue protocol-defined assessments and treatment.
Timeline
- Start
- 2018-11-08
- Primary completion
- 2022-10-03
- Completion
- 2025-03-03
Outcome
Met primary endpoint
registry analysis (superiority test); Pembrolizumab + Chemotherapy (FP or CAPOX Regimen) vs Placebo + Chemotherapy (FP or CAPOX Regimen); p <0.0001 NCT03675737 ↗
registry Hazard Ratio (HR) 0.78 (95% CI 0.70 to 0.87); Log Rank NCT03675737 ↗
registry Hazard Ratio (HR) 0.74 (95% CI 0.65 to 0.84); Log Rank NCT03675737 ↗
registry Hazard Ratio (HR) 0.65 (95% CI 0.53 to 0.79); Log Rank NCT03675737 ↗
Publications
- Results Rha SY, Oh DY, Yanez P, Bai Y, Ryu MH, Lee J, Rivera F, Alves GV, Garrido M, Shiu KK, Fernandez MG, Li J, Lowery MA, Cil T, Cruz FM, Qin S, Luo S, Pan H, Wainberg ZA, Yin L, Bordia S, Bhagia P, Wyrwicz LS; KEYNOTE-859 investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Nov;24(11):1181-1195. doi: 10.1016/S1470-2045(23)00515-6. Epub 2023 Oct 21.
- Results Qin S, Bai Y, Li J, Pan H, Luo S, Qu Y, Ye F, Yang L, Liu T, Li W, Chen X, Yang J, Ying J, Lin X, Zhao L, Liang X, Mao Y, Guo R, Zuo Y, Bordia S, Li S. First-Line Pembrolizumab Plus Chemotherapy for HER2-Negative Advanced Gastric Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-859 Study. Adv Ther. 2025 Apr;42(4):1892-1906. doi: 10.1007/s12325-024-03069-4. Epub 2025 Mar 1.
- Wyrwicz L, Kalampoki V, Valderrama A, Young K. Pembrolizumab plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction cancer: KEYNOTE-859 Q-TWiST analysis. Immunotherapy. 2026 Feb;18(3):161-167. doi: 10.1080/1750743X.2026.2647579. Epub 2026 Apr 11.
- Yasui H, Aizawa M, Yamaguchi K, Kawazoe A, Hara H, Tsuda M, Shoji H, Sugimoto N, Shibata N, Amagai K, Choda Y, Iwagami S, Esaki T, Kadowaki S, Shiratori S, Han S, Bordia S, Shitara K. First-line pembrolizumab plus chemotherapy for participants in Japan with gastric or gastroesophageal junction adenocarcinoma: subgroup analysis of the phase 3 KEYNOTE-859 study. Int J Clin Oncol. 2025 Oct;30(10):2003-2011. doi: 10.1007/s10147-025-02847-6. Epub 2025 Aug 1.
- Tabernero J, Bang YJ, Van Cutsem E, Fuchs CS, Janjigian YY, Bhagia P, Li K, Adelberg D, Qin SK. KEYNOTE-859: a Phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma. Future Oncol. 2021 Aug;17(22):2847-2855. doi: 10.2217/fon-2021-0176. Epub 2021 May 12.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |
| Background | Capecitabine | Small molecule | 1000 mg/m2 | Oral |
| Background | Cisplatin | Other / unclassified | 80 mg/m2 | Intravenous |
| Background | Oxaliplatin | Small molecule | 130 mg/m2 | Intravenous |
| Background | fluorouracil | Small molecule | 800 mg/m2 | Intravenous |