Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Biliary Tract Carcinoma

Treatments: Drug: Cisplatin; Drug: Gemcitabine; Biological: Pembrolizumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04003636

3475-966

2019-000944-82 (EudraCT Number)

2023-506657-38-00 (Registry Identifier)

MK-3475-966 (Other Identifier)

U1111-1294-1943 (Registry Identifier)

KEYNOTE-966 (Other Identifier)

195007 (Registry Identifier)

Details and patient eligibility

About

This is a study of pembrolizumab plus gemcitabine/cisplatin versus placebo plus gemcitabine/cisplatin as first-line therapy in participants with advanced and/or unresectable biliary tract carcinoma. The primary hypothesis is pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).

Enrollment: 1,069 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or gallbladder cancer)
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the site investigator
• Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria
• Is able to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion
• Has a life expectancy of greater than 3 months
• Has adequate organ function

Exclusion Criteria

• Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer)
• Has ampullary cancer
• Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms
• Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 or 2 (anti-PD-L1, anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator
• Has had an allogenic tissue/solid organ transplant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,069 participants in 2 patient groups, including a placebo group

Arm A (Pembrolizumab+Chemotherapy)

Experimental group

Description:

Participants receive pembrolizumab, 200 mg intravenous (IV) infusion, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS gemcitabine, 1000 mg/m\^2, IV infusion Q3W, Day 1 and Day 8 of each 3-week cycle until progressive disease or unacceptable toxicity PLUS cisplatin, 25 mg/m\^2 IV infusion, Q3W, Day 1 and Day 8 of each 3-week cycle for up to 8 cycles. Eligible participants who stop the initial course of pembrolizumab with stable disease (SD) or better but progress after discontinuation will initiate a second course of pembrolizumab 200 mg IV Q3W, Day 1 of each 3-week cycle for up to 17 cycles. Treatment with gemcitabine can be stopped at anytime in first or second course due to toxicity or disease progression.

Treatment:

Drug: Gemcitabine

Biological: Pembrolizumab

Drug: Cisplatin

Arm B (Placebo+Chemotherapy)

Placebo Comparator group

Description:

Participants receive placebo to pembrolizumab, 200 mg IV infusion, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS gemcitabine, 1000 mg/m\^2 IV infusion, Q3W, Day 1 and Day 8 of each 3-week cycle until progressive disease or unacceptable toxicity PLUS cisplatin, 25 mg/m\^2 IV infusion, Q3W, Day 1 and Day 8 of each 3-week cycle for up to 8 cycles.

Treatment:

Drug: Placebo

Drug: Gemcitabine

Drug: Cisplatin