NCT03615326

Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)

A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 738 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).

Detailed description

Pembrolizumab (200 mg) or placebo will be administered intravenously \[IV\] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will either be FP (80 mg/m\^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800 mg/m\^2 5-fluorouracil \[5-FU\] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000 mg/m\^2 capecitabine administered orally twice daily \[BID\] on days 1-14 of each 3-week cycle and 130 mg/m\^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine \[CDHP\], and potassium oxonate \[Oxo\]) administered orally BID according to Body Surface Area (BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m\^2) administered IV on Day 1 each 3-week cycle.

Conditions

• Gastric Neoplasms
• Gastroesophageal Junction Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Pembrolizumab	200 mg on Day 1 of each 3-week cycle as an IV infusion.
BIOLOGICAL	Placebo	Solution for IV infusion on Day 1 of each 3-week cycle.
DRUG	Cisplatin	80 mg/m\^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.
DRUG	5-FU	800 mg/m\^2/day continuous on Days 1-5 of each 3-week cycle (120 hours or per local standard), administered as part of FP chemotherapy regimen.
DRUG	Oxaliplatin	130 mg/m\^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.
DRUG	Capecitabine	1000 mg/m\^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.
DRUG	S-1	Combination product of tegafur, CDHP, and Oxo. Oral capsules BID on Days 1-14 of each 3-week cycle based on body surface area (BSA): \<1.25 m\^2 BSA =40 mg, 1.25 to \<1.5 m\^2 BSA=50 mg, ≥1.5 m\^2 BSA=60 mg. Administered as part of SOX chemotherapy regimen.
BIOLOGICAL	Trastuzumab	8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.

Timeline

• Start date: 2018-10-05
• Primary completion: 2024-03-20
• Completion: 2025-11-12
• First posted: 2018-08-03
• Last updated: 2025-12-11
• Results posted: 2025-03-17

Locations

192 sites across 20 countries: United States, Australia, Brazil, Chile, China, France, Germany, Guatemala, Ireland, Israel, Italy, Japan, New Zealand, Poland, Russia, South Korea, Spain, Turkey (Türkiye), Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study