Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Gastric Adenocarcinoma

Treatments: Drug: Cisplatin; Drug: Capecitabine; Drug: 5-FU; Biological: Pembrolizumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02494583

163187 (Registry Identifier)

3475-062

MK-3475-062 (Other Identifier)

KEYNOTE-062 (Other Identifier)

2015-000972-88 (EudraCT Number)

Details and patient eligibility

About

This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants whose tumors express programmed death-ligand 1 (PD-L1) will be randomly assigned to one of the three treatment arms of the study: pembrolizumab as monotherapy [pembro mono], pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine [pembro combo], or placebo plus SOC chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine [SOC].

The primary study hypotheses are that pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of Progression-free Survival (PFS) and Overall Survival (OS) in participants with PD-L1 Combined Positive Score (CPS) ≥1, pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥10, pembrolizumab monotherapy is non-inferior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1, and pembrolizumab monotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1 and in participants with PD-L1 CPS ≥10.

Full description

As specified by the protocol, primary and secondary efficacy analyses will be evaluated in gastric cancer participants with PD-L1 CPS ≥1 (all participants) and PD-L1 CPS ≥10 (OS) by comparing the pembro mono arm or pembro combo arm separately to the SOC arm.

Enrollment: 763 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to first dose of study medication
• Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma
• Human epidermal growth factor receptor 2- (HER2/neu-) negative and programmed cell death ligand 1 (PD-L1)-positive
• Has measurable disease
• Female participants of childbearing potential must be willing to use adequate contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• Male participants of childbearing potential should agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
• Adequate organ function

Exclusion criteria

• Squamous cell or undifferentiated gastric cancer
• Previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participant may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization
• Major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment.
• Radiotherapy within 14 days of randomization
• Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in past 2 years
• 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 7 days prior the first dose of study medication
• History of non-infectious pneumonitis that required steroids or current pneumonitis
• Active infection requiring systemic therapy
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study medication
• Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or C
• Currently participating in and receiving study therapy or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study medication
• Received a live vaccine within 30 days prior to the first dose of study medication

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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763 participants in 3 patient groups, including a placebo group

Pembrolizumab Monotherapy (Pembro Mono)

Experimental group

Description:

Participants will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W). Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Treatment:

Biological: Pembrolizumab

Pembrolizumab + SOC Chemotherapy (Pembro Combo)

Experimental group

Description:

Participants will receive pembrolizumab 200 mg Q3W plus cisplatin 80 mg/m\^2 Q3W plus 5-FU 800 mg/m\^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m\^2 twice a day (BID) on Days 1-14 Q3W may be substituted for 5-FU per local guidelines. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Treatment:

Drug: Cisplatin

Biological: Pembrolizumab

Drug: 5-FU

Drug: Capecitabine

Placebo + SOC Chemotherapy (SOC)

Placebo Comparator group

Description:

Participants receive placebo IV Q3W plus cisplatin 80 mg/m\^2 Q3W plus 5-FU 800 mg/m\^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m\^2 BID on Days 1-14 Q3W may be substituted for 5-FU per local guidelines.

Treatment:

Drug: Cisplatin

Drug: 5-FU

Drug: Capecitabine

Drug: Placebo