A Phase 3 Randomized, Double Blind 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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Biliary Tract Carcinoma
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 158
- Locations
- 44
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 17 days ago
Overview
Brief Summary
In this China Extension study, pembrolizumab plus gemcitabine/cisplatin will be compared with placebo plus gemcitabine/cisplatin as first-line therapy in Chinese adults 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).
Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-3475-966 (NCT04003636) plus those enrolled during the China extension enrollment period. A total of approximately 158 Chinese participants will be enrolled.
Investigators
Eligibility 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
Arms & Interventions
Arm B: Placebo + Chemotherapy
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.
Intervention: Placebo
Arm A: Pembrolizumab + Chemotherapy
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 any time in first or second course due to toxicity or disease progression.
Intervention: Cisplatin
Arm B: Placebo + Chemotherapy
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.
Intervention: Cisplatin
Arm B: Placebo + Chemotherapy
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.
Intervention: Gemcitabine
Arm A: Pembrolizumab + Chemotherapy
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 any time in first or second course due to toxicity or disease progression.
Intervention: Pembrolizumab
Arm A: Pembrolizumab + Chemotherapy
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 any time in first or second course due to toxicity or disease progression.
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to approximately 29 months
Overall survival was defined as the time from randomization to death due to any cause. Per protocol the final reported outcome for OS did not include any sensitivity or supportive analysis.
Secondary Outcomes
- Progression-free Survival (PFS) Per RECIST 1.1 as Assessed by BICR(Up to approximately 29 months)
- Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)(Up to approximately 29 months)
- Number of Participants Who Experience One or More Adverse Events (AE)(Up to approximately 29 months)
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)(Up to approximately 29 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 29 months)
- Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by BICR(Up to approximately 29 months)
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 29 months)
- Number of Participants Who Experienced One or More Adverse Events (AEs)(Up to approximately 29 months)
- Number of Participants Who Discontinued Study Intervention Due to an AE(Up to approximately 29 months)