A Phase 3, Randomized, Double-blind Clinical Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-line Treatment in Participants With HER2 Negative, Previously Untreated, Unresectable or Metastatic Gastric Orgastroesophageal Junction Adenocarcinoma (KEYNOTE-859)
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Stomach Neoplasms
- Sponsor
- Merck Sharp & Dohme LLC
- Locations
- 28
- Primary Endpoint
- Overall Survival (OS)
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief 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 Chinese participants.
The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS).
Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-3475-859 (NCT03675737) plus those enrolled during the China extension enrollment period. A total of approximately 231 Chinese participants will be enrolled.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Pembrolizumab + FP or CAPOX
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Intervention: Pembrolizumab
Pembrolizumab + FP or CAPOX
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Intervention: Oxaliplatin
Pembrolizumab + FP or CAPOX
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Intervention: Cisplatin
Pembrolizumab + FP or CAPOX
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Intervention: 5-fluorouracil
Pembrolizumab + FP or CAPOX
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Intervention: Capecitabine
Placebo + FP or CAPOX
Participants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Intervention: Cisplatin
Placebo + FP or CAPOX
Participants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Intervention: 5-fluorouracil
Placebo + FP or CAPOX
Participants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Intervention: Oxaliplatin
Placebo + FP or CAPOX
Participants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Intervention: Capecitabine
Placebo + FP or CAPOX
Participants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Intervention: Placebo for Pembrolizumab
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to approximately 65 months
OS is the time from randomization to death due to any cause.
Secondary Outcomes
- Progression-free Survival (PFS)(Up to approximately 65 months)
- Objective Response Rate (ORR)(Up to approximately 65 months)
- Percentage of Participants Discontinuing Study Drug Due to AEs(Up to approximately 36 months)
- Percentage of Participants Experiencing Adverse Events (AEs)(Up to approximately 65 months)
- Duration of Response (DOR)(Up to approximately 65 months)