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

Merck Sharp & Dohme (MSD)

Status and phase

Completed

Phase 3

Conditions

Gastroesophageal Junction Cancer

Gastric Cancer

Treatments

Biological: Pembrolizumab

Drug: Docetaxel

Drug: 5-fluorouracil

Drug: Placebo

Drug: Leucovorin

Drug: Capecitabine

Drug: Cisplatin

Drug: Oxaliplatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT04882241

PHRR200226-002534 (Registry Identifier)

KEYNOTE-585 (Other Identifier)

173786 (Registry Identifier)

MK-3475-585 (Other Identifier)

3475-585 China Extension

Details and patient eligibility

About

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.

Full 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.

Enrollment

120 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

120 participants in 4 patient groups, including a placebo group

Pembrolizumab+XP/FP

Experimental group

Description:

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.

Treatment:

Drug: Capecitabine

Drug: Cisplatin

Drug: 5-fluorouracil

Biological: Pembrolizumab

Placebo+XP/FP

Placebo Comparator group

Description:

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.

Treatment:

Drug: Capecitabine

Drug: Cisplatin

Drug: Placebo

Drug: 5-fluorouracil

Pembrolizumab+FLOT Cohort

Experimental group

Description:

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.

Treatment:

Drug: Oxaliplatin

Drug: Leucovorin

Drug: 5-fluorouracil

Drug: Docetaxel

Biological: Pembrolizumab

Placebo+FLOT Cohort

Placebo Comparator group

Description:

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.

Treatment:

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Placebo

Drug: 5-fluorouracil

Drug: Docetaxel

Trial documents