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)

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).

Timeline

Start

2019-09-24

Primary completion

2022-12-15

Completion

2025-04-01

Outcome

Met primary endpoint

registry Arm A: Pembrolizumab + Chemotherapy vs Arm B: Placebo + Chemotherapy; p = 0.0034 NCT04003636 ↗

Publications

• Results Kelley 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.
• Ren 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 May 23. doi: 10.1007/s12325-026-03578-4. Online ahead of print.
• Jiang 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.
• Luo 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.
• Keller 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.

Drugs

Indications