Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for advanced biliary tract cancer (KEYNOTE-966) - a randomised, double-blind, placebo-controlled phase 3 trial

Sep 2, 2026

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Biliary tract cancers, including intrahepatic or extrahepatic bile duct and gallbladder tumors, have a poor prognosis and increasing global incidence. Standard advanced treatment combines gemcitabine with cisplatin, yet immune-suppressed tumor microenvironments limit response to checkpoint inhibitor monotherapy. KEYNOTE-966 evaluated whether adding pembrolizumab to gemcitabine/cisplatin improves outcomes versus gemcitabine/cisplatin plus placebo in previously untreated unresectable, locally advanced or metastatic disease.

LanguageEnglish

CategoryGeneral

FormatDOCX

Pages61

Reading Time21 min

AccessFree to download

Background

Methods

Findings

Study design and endpoints

Article Type: Fast-track Article - Randomised Controlled Trial Title: Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled phase 3 trial Authors: Prof Robin Kate Kelley, MD,1* Makoto Ueno, MD,2* Prof Changhoon Yoo, MD,3 Prof Richard S Finn, MD,4 Prof Junji Furuse, MD,5 Prof Zhenggang Ren, MD,6 Thomas Yau, MD,7 Heinz-Josef Klümpen, PhD,8 Prof Stephen L Chan, MD,9 Masato Ozaka, MD,10 Prof Chris Verslype, MD,11 Mohamed Bouattour, MD,12 Prof Joon Oh Park, MD,13 Olga Barajas, MD,14 Uwe Pelzer, MD,15 Prof Juan W Valle, MD,16 Li Yu, PhD,17 Usha Malhotra, MD,18 Abby B Siegel, MD,18 Prof Julien Edeline, PhD,19 Prof Arndt Vogel, MD20* on behalf of the KEYNOTE-966 Investigators† Affiliations: 1Department of Medicine (Hematology/Oncology), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; 2Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan; 3Department of Oncology, Asan Medical Center; University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 5Department of Medical Oncology, Kyorin University Hospital, Tokyo, Japan (currently affiliated with Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan); 6Department of Hepatic Oncology, Liver Cancer Institute of Zhongshan Hospital, Fudan University, National Clinical Research Center for Interventional Medicine, Shanghai, China; 7Department of Medicine, University of Hong Kong, Hong Kong, China; 8Department of Medical Oncology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Amsterdam, the Netherlands; 9State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir Yue-Kong Pao Center for Cancer, the Chinese University of Hong Kong, Hong Kong; 10Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan; 11Digestive Oncology, University Hospitals Leuven, Leuven, Belgium; 12Liver Cancer Unit, Hôpital Beaujon, Clichy, France; 13Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 14Department of Medical Oncology, Arturo López Pérez Foundation, Santiago, Chile; 15Department of Hematology, Oncology and Cancer Immunology, Charite Campus Mitte, Freie Universität Berlin, Humboldt Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; 16Division of Cancer Sciences, University of Manchester and Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; 17Biostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, NJ, USA; 18Global Clinical Development, Merck & Co., Inc., Rahway, NJ, USA; 19INSERM, University Rennes, Department of Medical Oncology, CLCC Eugène Marquis, COSS (Chemistry Oncogenesis Signaling), Rennes, France; 20Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany *Drs. Kelley, Ueno, and Vogel contributed equally to this article. †The KEYNOTE-966 Investigators are listed in the appendix (pp 2-4). Address for Correspondence Prof Arndt Vogel, MD Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School Carl-Neuberg-Str.1, 30625 Hannover, Germany Email: vogel.arndt@mh-hannover.de Tel: +49 511 532 9590 Summary Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer has been chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint

FAQs

What question did KEYNOTE-966 address?

Whether adding pembrolizumab to gemcitabine and cisplatin improves outcomes compared with gemcitabine and cisplatin alone in advanced biliary tract cancer.

How were participants assigned and what treatment schedules were used?

Participants were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks, each combined with gemcitabine on days 1 and 8 every 3 weeks and cisplatin on days 1 and 8 every 3 weeks.

What were the primary outcome and its main results?

Overall survival was the primary endpoint. Median overall survival was 12.7 months with pembrolizumab plus gemcitabine/cisplatin versus 10.9 months with placebo plus gemcitabine/cisplatin, with a hazard ratio of 0.83.

Sep 2, 2026

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