Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)

Conditions

• Gastric Cancer
• Gastroesophageal Junction Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — BIOLOGICAL
  IV infusion
• Placebo — DRUG
  IV infusion
• Cisplatin — DRUG
  IV infusion
• Capecitabine — DRUG
  Oral tablets
• 5-fluorouracil — DRUG
  IV infusion
• Docetaxel — DRUG
  IV infusion
• Oxaliplatin — DRUG
  IV infusion
• Leucovorin — DRUG
  IV infusion

Study Details

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The primary study hypotheses are that: * Neoadjuvant and adjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab is superior to neoadjuvant and adjuvant placebo plus chemotherapy, followed by adjuvant placebo in terms of Event-free Survival (EFS) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), and * Neoadjuvant pembrolizumab plus chemotherapy is superior to neoadjuvant placebo plus chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery. With Amendment 10, upon study completion, participants will be discontinued and may be enrolled in an extension study.

Key Dates

Start date

Oct 9, 2017

Status verified

Feb 2026

Primary completion

Feb 16, 2024

Completion

Apr 23, 2025

Study Design

Enrollment

1,007 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Pembrolizumab + XP/FP
  XP=cisplatin+capecitabine and FP=cisplatin+5-fluorouracil. Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2 continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of pembrolizumab 200 mg IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by pembrolizumab monotherapy 200 mg IV infusion on Day 1 Q3W for up to 11 additional cycles.
• Placebo Comparator: Placebo + XP/FP
  Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles.
• Experimental: Pembrolizumab+FLOT Cohort
  FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations). Adjuvant: 4 to 10 weeks postsurgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion Day 1 Q3W PLUS docetaxel 50 mg/m\^2, oxaliplatin 85 mg/m\^2, 5FU 2600 mg/m\^2, and leucovorin 200 mg/m\^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by pembrolizumab monotherapy 200 mg via IV infusion on Day 1 Q3W for up to 11 additional cycles.
• Placebo Comparator: Placebo+FLOT Cohort
  Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations). Adjuvant: 4 to 10 weeks postsurgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles.

Primary Outcome Measure

Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms [ Time Frame: Up to approximately 75 months ]

Locations (14)

Related coverage on Hipa.ai

• Pembrolizumab Extends Event-free Survival in Gastric/GEJ Adenocarcinoma
  Pembrolizumab · Feb 20, 2025 · ClinicalTrials.gov

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