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)-China Extension Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Biliary Tract Carcinoma

Intervention / Treatment
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* Biological: Pembrolizumab
* Drug: Gemcitabine
* Drug: Cisplatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Pembrolizumab+Gemcitabine+Cisplatin)<br>Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. | Biological: Pembrolizumab<br>* Pembrolizumab by intravenous (IV) infusion<br>* Other names: MK-3475;Drug: Gemcitabine<br>* Gemcitabine by IV infusion<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin by IV infusion<br>* Other names: Platinol®-AQ;|
| Placebo Comparator: Arm B (Placebo+Gemcitabine+Cisplatin)<br>Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. | Drug: Gemcitabine<br>* Gemcitabine by IV infusion<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin by IV infusion<br>* Other names: Platinol®-AQ;Drug: Placebo<br>* Placebo to pembrolizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | 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. | Up to approximately 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Per RECIST 1.1 as Assessed by BICR | Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurred first. | 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) | ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which was adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ. | Up to approximately 29 months | 
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR | For participants who demonstrated a confirmed CR or PR, DOR was the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first. | Up to approximately 29 months | 
| Number of Participants Who Experience One or More Adverse Events (AE) | An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. | Up to approximately 29 months | 
| Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) | An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. | Up to approximately 29 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed cell death 1 (PD-1), Pembrolizumab, Cholangiocarcinoma, Gallbladder cancer, Checkpoint inhibitor, Immunotherapy, Biliary, Keytruda, Bile Duct Cancer