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)

Phase 3

Completed

• Conditions: Biliary Tract Carcinoma
• Interventions: Biological: Pembrolizumab; Drug: Gemcitabine; Drug: Placebo; Drug: Cisplatin

• Registration Number: NCT04003636
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-28
• Study First Submitted QC: 2019-06-28
• Study First Posted: 2019-07-01
• Study Start: 2019-09-24
• Primary Completion: 2022-12-15
• Results First Submitted: 2023-12-06
• Results First Submitted QC: 2023-12-06
• Results First Posted: 2023-12-22
• Status Verified: 2025-04
• Study Completion: 2025-04-01
• Last Update Submitted: 2025-04-16
• Last Update Posted: 2025-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1069

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Gemcitabine	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.
Arm B (Placebo+Gemcitabine+Cisplatin)	Gemcitabine	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.
Arm B (Placebo+Gemcitabine+Cisplatin)	Placebo	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.
Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Pembrolizumab	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.
Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Cisplatin	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.
Arm B (Placebo+Gemcitabine+Cisplatin)	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to approximately 38 months	Overall survival was defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	Up to approximately 38 months	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 occurs during the course of the study.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (BICR)	Up to approximately 26 months	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR, or death due to any cause, whichever occurred first.
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 26 months	ORR was defined as the percentage of participants who have 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.
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 38 months	For participants who demonstrate 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.
Number of Participants Who Experience One or More Adverse Events (AE)	Up to approximately 38 months	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.

Trial Locations

Locations (185)

University of Alabama at Birmingham Comprehensive Cancer Ctr ( Site 0016); 🇺🇸 Birmingham, Alabama, United States

University of California San Diego Moores Cancer Center ( Site 0008); 🇺🇸 La Jolla, California, United States

UCLA Hematology/Oncology - Santa Monica ( Site 0014); 🇺🇸 Los Angeles, California, United States

University of California - San Francisco ( Site 0030); 🇺🇸 San Francisco, California, United States

University of Colorado Hospital ( Site 0011); 🇺🇸 Aurora, Colorado, United States

Hartford Hospital ( Site 0057); 🇺🇸 Hartford, Connecticut, United States

Yale University ( Site 0053); 🇺🇸 New Haven, Connecticut, United States

Winship Cancer Institute of Emory University ( Site 0013); 🇺🇸 Atlanta, Georgia, United States

Northwest Georgia Oncology Centers PC ( Site 0045); 🇺🇸 Marietta, Georgia, United States

Decatur Memorial Hospital ( Site 0056); 🇺🇸 Decatur, Illinois, United States

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