Clinical trial · Interventional
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)
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
NCT04003636CI-TRIAL-00106320KEYNOTE-966completedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Biliary Tract Carcinoma | Biliary Tract Carcinoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cisplatin | Drug | Cisplatin | ALIAS |
| Gemcitabine | Drug | Gemcitabine | ALIAS |
| Pembrolizumab | Biological | Pembrolizumab | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A (Pembrolizumab+Chemotherapy)
- description
- 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 anytime in first or second course due to toxicity or disease progression.
- interventionNames
- Biological: Pembrolizumab
- Drug: Gemcitabine
- Drug: Cisplatin
- type
- PLACEBO_COMPARATOR
- label
- Arm B (Placebo+Chemotherapy)
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (5)
- RESULTKelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16. PMID 37075781
- DERIVEDRen Z, Liang T, Gu S, Gou H, Peng C, Pan Y, Song T, Su H, Cao K, Liang H, Ying J, Geng Z, Yu W, Zhao H, Bai Y, Hao C, Mao Y, Li W, Wang L, Li D, Wang W, Li N, Malhotra U, Qin S. First-Line Pembrolizumab Plus Chemotherapy for Advanced Biliary Tract Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-966 Study. Adv Ther. 2026 Sep;43(9):3871-3885. doi: 10.1007/s12325-026-03578-4. Epub 2026 May 23. PMID 42176183
- DERIVEDJiang C, Zhou K, Shu P. Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: perspectives from US and Chinese payers. BMJ Open. 2025 Apr 23;15(4):e094047. doi: 10.1136/bmjopen-2024-094047. PMID 40268484
- DERIVEDLuo X, Cai T, Wu J, Li X, Wang X, Ma H. Cost-effectiveness of pembrolizumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced biliary tract cancer in China and the US. Front Pharmacol. 2024 Aug 14;15:1393559. doi: 10.3389/fphar.2024.1393559. eCollection 2024. PMID 39206260
- DERIVEDKeller HR, Fluke L, Forrester JA, Wolf RF. Identifying Indications for Neoadjuvant Therapy in Cholangiocarcinoma. Oncology (Williston Park). 2024 Apr 11;38(4):160-162. doi: 10.46883/2024.25921017. PMID 38661512