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

NCT04924062 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 3475-966 China ExtensionMK-3475-966KEYNOTE-966195007
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 22

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).

Conditions

Biliary Tract Carcinoma

Keywords

Programmed cell death 1 (PD-1); Pembrolizumab; Cholangiocarcinoma; Gallbladder cancer; Checkpoint inhibitor; Immunotherapy; Biliary; Keytruda; Bile Duct Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• Duration of Response (DOR) 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

Study Arms (2)

Arm A: Pembrolizumab + Chemotherapy

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: Gemcitabine; Drug: Cisplatin

Arm B: Placebo + Chemotherapy

PLACEBO COMPARATOR

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.

Drug: Gemcitabine; Drug: Cisplatin; Drug: Placebo

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab by intravenous (IV) infusion

Also known as: MK-3475

Arm A: Pembrolizumab + Chemotherapy

Gemcitabine DRUG

Gemcitabine by IV infusion

Also known as: Gemzar

Arm A: Pembrolizumab + Chemotherapy; Arm B: Placebo + Chemotherapy

Cisplatin DRUG

Cisplatin by IV infusion

Also known as: Platinol®, Platinol®-AQ

Arm A: Pembrolizumab + Chemotherapy; Arm B: Placebo + Chemotherapy

Placebo DRUG

Placebo to pembrolizumab by IV infusion

Arm B: Placebo + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (22)

Anhui Provincial Hospital ( Site 0140)

Hefei, Anhui, 230001, China

Location

Beijing Cancer Hospital ( Site 0138)

Beijing, Beijing Municipality, 100036, China

Location

Peking Union Medical College Hospital ( Site 0150)

Beijing, Beijing Municipality, 100730, China

Location

First Affiliated Hospital of The Third Military Medical University ( Site 0130)

Chongqing, Chongqing Municipality, 400038, China

Location

Fujian Provincial Cancer Hospital ( Site 0154)

Fuzhou, Fujian, 350014, China

Location

900 Hospital of the Joint ( Site 0137)

Fuzhou, Fujian, 350025, China

Location

Guangdong Provincial People s Hospital ( Site 0161)

Guangzhou, Guangdong, 510080, China

Location

Harbin Medical University Cancer Hospital ( Site 0133)

Harbin, Heilongjiang, 610000, China

Location

Hunan Provincial People Hospital ( Site 0142)

Changsha, Hunan, 410005, China

Location

Hunan Cancer Hospital ( Site 0132)

Changsha, Hunan, 410013, China

Location

The Third Xiangya Hospital of Central South University ( Site 0157)

Changsha, Hunan, 410013, China

Location

The 81st Hospital of PLA ( Site 0128)

Nanjing, Jiangsu, 210031, China

Location

The First Hospital of Jilin University ( Site 0131)

Changchun, Jilin, 130021, China

Location

Zhongshan Hospital Fudan University ( Site 0129)

Shanghai, Shanghai Municipality, 200032, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0158)

Shanghai, Shanghai Municipality, 200127, China

Location

Fudan University Shanghai Cancer Center ( Site 0160)

Shanghai, Shanghai Municipality, 201315, China

Location

Tangdu Hospital ( Site 0146)

Xi’an, Shanxi, 710038, China

Location

The First Affiliated Hospital of Xi an Jiaotong University ( Site 0145)

Xi’an, Shanxi, 710048, China

Location

West China Hospital of Sichuan University ( Site 0147)

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute & Hospital ( Site 0155)

Tianjin, Tianjin Municipality, 300060, China

Location

The First Affiliated Hospital Zhejiang University ( Site 0136)

Hangzhou, Zhejiang, 310003, China

Location

Zhejiang Cancer Hospital ( Site 0134)

Hangzhou, Zhejiang, 310022, China

Location

Related Publications (1)

• Yoo C, Ueno M, Klumpen HJ, Kelley RK, Vogel A, Furuse J, Ren Z, Yau T, Chan SL, Ozaka M, Oh SC, Gu S, Park JO, Valle JW, Edeline J, Kim JG, Kamble S, Norquist JM, Yu L, Malhotra U, Finn RS. Health-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study. J Hepatol. 2025 Sep;83(3):692-700. doi: 10.1016/j.jhep.2025.03.019. Epub 2025 Mar 27.

  PMID: 40154623 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms

Interventions

pembrolizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Bile Duct Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 11, 2021
• Study Start: July 10, 2020
• Primary Completion: December 15, 2022
• Study Completion: March 25, 2025
• Last Updated: April 15, 2026
• Results First Posted: December 26, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (22)