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) (KEYNOTE-966)
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ClinicalTrials.gov Identifier: NCT04003636 |
Recruitment Status :
Active, not recruiting
First Posted : July 1, 2019
Last Update Posted : January 12, 2023
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Condition or disease | Intervention/treatment | Phase |
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Biliary Tract Carcinoma | Biological: Pembrolizumab Drug: Gemcitabine Drug: Cisplatin Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 1069 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | September 24, 2019 |
Actual Primary Completion Date : | December 15, 2022 |
Estimated Study Completion Date : | November 29, 2024 |

Arm | Intervention/treatment |
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Experimental: Arm A (Pembrolizumab+Gemcitabine+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.
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Biological: Pembrolizumab
Pembrolizumab by intravenous (IV) infusion
Other Name: MK-3475 Drug: Gemcitabine Gemcitabine by IV infusion
Other Name: Gemzar Drug: Cisplatin Cisplatin by IV infusion
Other Names:
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Placebo Comparator: Arm B (Placebo+Gemcitabine+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.
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Drug: Gemcitabine
Gemcitabine by IV infusion
Other Name: Gemzar Drug: Cisplatin Cisplatin by IV infusion
Other Names:
Drug: Placebo Placebo to pembrolizumab |
- Overall Survival (OS) [ Time Frame: Up to approximately 38 months ]Overall survival is defined as the time from randomization to death due to any cause.
- Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 26 months ]Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs 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) [ Time Frame: Up to approximately 26 months ]ORR is 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 is 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 [ Time Frame: Up to approximately 38 months ]For participants who demonstrate a confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
- Number of Participants Who Experience One or More Adverse Events (AE) [ Time Frame: Up to approximately 38 months ]An adverse event (AE) is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study.
- Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) [ Time Frame: Up to approximately 38 months ]An AE is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04003636

Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Responsible Party: | Merck Sharp & Dohme LLC |
ClinicalTrials.gov Identifier: | NCT04003636 |
Other Study ID Numbers: |
3475-966 MK-3475-966 ( Other Identifier: Merck ) KEYNOTE-966 ( Other Identifier: Merck ) 195007 ( Registry Identifier: JAPIC-CTI ) 2019-000944-82 ( EudraCT Number ) |
First Posted: | July 1, 2019 Key Record Dates |
Last Update Posted: | January 12, 2023 |
Last Verified: | January 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
URL: | http://engagezone.msd.com/ds_documentation.php |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Programmed cell death 1 (PD-1) Pembrolizumab Cholangiocarcinoma Gallbladder cancer Checkpoint inhibitor |
Immunotherapy Biliary Keytruda Bile Duct Cancer |
Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Gemcitabine Cisplatin Pembrolizumab Antineoplastic Agents Antimetabolites, Antineoplastic |
Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Immunological |