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

NCT04882241 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: 3475-585 China ExtensionMK-3475-585173786KEYNOTE-585PHRR200226-002534
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 20

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.

Conditions

Gastric Cancer; Gastroesophageal Junction Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (5)

• 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

  EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.

  Up to approximately 42 months

• Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  PathCR rate is defined as the percentage of participants having a pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.

  Up to approximately 9 weeks following completion of neoadjuvant treatment (up to Study Week 18)

• Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  OS is defined as the time from randomization to death due to any cause. OS is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.

  Up to approximately 42 months

• Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The FLOT cohort was not enrolled in China per specifications in the protocol Supplemental Statistical Analysis Plan (sSAP) amendment and no data were collected for the FLOT cohort in China.

  Up to approximately 42 months

• Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The FLOT cohort was not enrolled in China per specifications in the protocol sSAP amendment and no data were collected for the FLOT cohort in China.

  Up to approximately 17 months

Secondary Outcomes (5)

• Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 42 months

• Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 23 months

• Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  Up to approximately 42 months

• Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 42 months

• 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 in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 42 months

Study Arms (4)

Pembrolizumab+XP/FP

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: Cisplatin; Drug: Capecitabine; Drug: 5-fluorouracil

Placebo+XP/FP

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Cisplatin; Drug: Capecitabine; Drug: 5-fluorouracil

Pembrolizumab+FLOT Cohort

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: 5-fluorouracil; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Leucovorin

Placebo+FLOT Cohort

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: 5-fluorouracil; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Leucovorin

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab+FLOT Cohort; Pembrolizumab+XP/FP

Placebo DRUG

IV infusion

Also known as: Normal saline solution

Placebo+FLOT Cohort; Placebo+XP/FP

Cisplatin DRUG

IV infusion

Also known as: PLATINOL®

Pembrolizumab+XP/FP; Placebo+XP/FP

Capecitabine DRUG

Oral tablets

Also known as: XELODA®

Pembrolizumab+XP/FP; Placebo+XP/FP

Docetaxel DRUG

IV infusion

Also known as: TAXOTERE®

Pembrolizumab+FLOT Cohort; Placebo+FLOT Cohort

Oxaliplatin DRUG

IV infusion

Also known as: ELOXATIN®

Pembrolizumab+FLOT Cohort; Placebo+FLOT Cohort

Leucovorin DRUG

IV infusion

Also known as: WELLCOVORIN®

Pembrolizumab+FLOT Cohort; Placebo+FLOT Cohort

5-fluorouracil DRUG

IV infusion

Also known as: ADRUCIL®, 5FU

Pembrolizumab+FLOT Cohort; Pembrolizumab+XP/FP; Placebo+FLOT Cohort; Placebo+XP/FP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 MSD pembrolizumab (MK-3475) clinical study.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (20)

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

Bengbu, Anhui, 233004, China

Location

Beijing Friendship Hospital ( Site 0637)

Beijing, Beijing Municipality, 100050, China

Location

Beijing Cancer Hospital ( Site 0221)

Beijing, Beijing Municipality, 100142, China

Location

Fujian Provincial Cancer Hospital ( Site 0230)

Fuzhou, Fujian, 350014, China

Location

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

Fuzhou Fujian, Fujian, 350001, China

Location

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

Guangzhou, Guangdong, 510080, China

Location

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

Guangzhou, Guangdong, 510120, China

Location

Fourth Hospital of Hebei Medical University ( Site 0633)

Shijiazhuang, Hebei, 050035, China

Location

Henan Cancer Hospital (Site 0227)

Zhengzhou, Henan, 450008, China

Location

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

Xuzhou, Jiangsu, 221006, China

Location

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

Changchun, Jilin, 130021, China

Location

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

Xi'an, Shaanxi, 710038, China

Location

Shandong Provincial Hospital-Gastrointestinal Surgery ( Site 0640)

Jinan, Shandong, 250001, China

Location

The Affiliated Hospital of Qingdao University ( Site 0636)

Qingdao, Shandong, 266003, China

Location

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

Shanghai, Shanghai Municipality, 200127, China

Location

Sichuan Cancer hospital

Chengdu, Sichuan, 610041, China

Location

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

Hangzhou, Zhejiang, 310014, China

Location

Zhejiang Cancer Hospital ( Site 0231)

Hangzhou, Zhejiang, 310022, China

Location

Sir Run Run Shaw Hospital ( Site 0233)

Hangzhou, Zhejiang, 430030, China

Location

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

Wenzhou, Zhejiang, 32500, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Stomach Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Saline Solution; Cisplatin; Capecitabine; Fluorouracil; Docetaxel; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC.

clinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 11, 2021
• Study Start: July 29, 2020
• Primary Completion: February 16, 2024
• Study Completion: April 23, 2025
• Last Updated: March 6, 2026
• Results First Posted: February 20, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (20)