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)-China Extension

NCT ID: NCT04882241

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-29
• Study Completion Date: 2025-04-23

Brief Summary

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 Chinese adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. No formal hypothesis testing will be done.

Detailed Description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-585 (NCT03221426) plus those enrolled during the China extension enrollment period. A total of approximately 120 Chinese participants will be enrolled.

Conditions

Gastric Cancer; Gastroesophageal Junction Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) via continuous IV infusion on Days 1 to 5 of each 3-week cycle.

Adjuvant: 4 to 10 weeks post-surgery, participants receive pembrolizumab 200 mg 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 via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 3 cycles.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Cisplatin

Intervention Type: DRUG

IV infusion

Capecitabine

Intervention Type: DRUG

Oral tablets

5-fluorouracil

Intervention Type: DRUG

IV infusion

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 via continuous IV infusion on Days 1 to 5 of each 3-week cycle.

Adjuvant: 4 to 10 weeks post-surgery, participants receive 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 via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 3 cycles.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

IV infusion

Cisplatin

Intervention Type: DRUG

IV infusion

Capecitabine

Intervention Type: DRUG

Oral tablets

5-fluorouracil

Intervention Type: DRUG

IV infusion

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 pembrolizumab 200 mg via IV infusion Day 1 Q3W for up to 11 cycles 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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

5-fluorouracil

Intervention Type: DRUG

IV infusion

Docetaxel

Intervention Type: DRUG

IV infusion

Oxaliplatin

Intervention Type: DRUG

IV infusion

Leucovorin

Intervention Type: DRUG

IV infusion

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 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

IV infusion

5-fluorouracil

Intervention Type: DRUG

IV infusion

Docetaxel

Intervention Type: DRUG

IV infusion

Oxaliplatin

Intervention Type: DRUG

IV infusion

Leucovorin

Intervention Type: DRUG

IV infusion

Interventions

Pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

Placebo

IV infusion

Intervention Type: DRUG

Cisplatin

IV infusion

Intervention Type: DRUG

Capecitabine

Oral tablets

Intervention Type: DRUG

5-fluorouracil

IV infusion

Intervention Type: DRUG

Docetaxel

IV infusion

Intervention Type: DRUG

Oxaliplatin

IV infusion

Intervention Type: DRUG

Leucovorin

IV infusion

Intervention Type: DRUG

Other Intervention Names

MK-3475; KEYTRUDA®; Normal saline solution; PLATINOL®; XELODA®; ADRUCIL®; 5FU; TAXOTERE®; ELOXATIN®; WELLCOVORIN®

Eligibility Criteria

Inclusion Criteria

• Has previously untreated localized gastric or gastroesophageal junction (GEJ) adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
• Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.
• Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.
• Has adequate organ function.
• Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
• Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
• Has life expectancy of greater than 6 months.

Exclusion Criteria

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
• Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment.
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
• Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of Hepatitis B or known active Hepatitis C virus infection.
• Has a known history of active tuberculosis (TB).
• Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
• Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.
• Has had an allogenic tissue/solid organ transplant.
• Has received a live vaccine within 30 days prior to the first dose of study treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Beijing Cancer Hospital ( Site 0221)

Beijing, Beijing Municipality, China

Fujian Provincial Cancer Hospital ( Site 0230)

Fuzhou, Fujian, China

Fujian Medical University Union Hospital-1 Bingfanglou-Gastric Surgery Department (Site 0632)

Fuzhou Fujian, Fujian, China

The First Affiliated Hospital, Sun Yat-sen University (Site 0635)

Guangzhou, Guangdong, China

The First Affiliated Hospital of Guangzhou Medical University ( Site 0224)

Guangzhou, Guangdong, China

Fourth Hospital of Hebei Medical University ( Site 0633)

Shijiazhuang, Hebei, China

Henan Cancer Hospital (Site 0227)

Zhengzhou, Henan, China

The Affiliated Hospital of Xuzhou Medical College-Oncology ( Site 0645)

Xuzhou, Jiangsu, China

The First Hospital of Jilin University-Gastrointestinal Surgery ( Site 0234)

Changchun, Jilin, China

Tangdu Hospital of Fourth Military Medical University of Chinese People's Liberation Army ( Site 0647)

Xi'an, Shaanxi, China

Shandong Provincial Hospital-Gastrointestinal Surgery ( Site 0640)

Jinan, Shandong, China

The Affiliated Hospital of Qingdao University ( Site 0636)

Qingdao, Shandong, China

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 0642)

Shanghai, Shanghai Municipality, China

Sichuan Cancer hospital

Chengdu, Sichuan, China

Zhejiang Provincial People's Hospital-Oncology (Site 0656)

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital ( Site 0231)

Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital ( Site 0233)

Hangzhou, Zhejiang, China

Afflilated Hospital of Bengbu Medical College-Surgical Oncology (Site 0638)

Bengbu, Anhui, China

Beijing Friendship Hospital ( Site 0637)

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Wenzhou Medical University (Site 0652)

Wenzhou, Zhejiang, China

Countries

China

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

MK-3475-585

Identifier Type: OTHER

Identifier Source: secondary_id

173786

Identifier Type: REGISTRY

Identifier Source: secondary_id

KEYNOTE-585

Identifier Type: OTHER

Identifier Source: secondary_id

PHRR200226-002534

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-585 China Extension

Identifier Type: -

Identifier Source: org_study_id