Abstract 78TiP
Background
Biliary tract cancer (BTC), comprising intra- and extra-hepatic cholangiocarcinoma and gallbladder cancer, is a rare and aggressive malignancy. Most patients (pts) present with advanced or unresectable disease, for which the current standard of care is gemcitabine plus cisplatin. Median survival for these pts is only 12 months, highlighting the need for more effective therapies. Pembrolizumab is a PD-1 inhibitor that has demonstrated modest antitumor activity as monotherapy in pts with previously treated BTC and has improved survival when used in combination with platinum-based chemotherapy in other cancer types.
Trial design
KEYNOTE-966 (NCT04003636) is a randomized, double-blind, phase III trial designed to evaluate the efficacy and safety of pembrolizumab plus gemcitabine and cisplatin versus placebo plus gemcitabine and cisplatin in pts with previously untreated advanced BTC. Key eligibility criteria include age ≥18 years, histologically confirmed metastatic or unresectable BTC, measurable disease per RECIST v1.1, ECOG performance status 0/1, and no prior systemic therapy for advanced BTC. Pts with past or ongoing hepatitis C or controlled hepatitis B virus infection are eligible per protocol-defined criteria. Approximately 788 pts will be randomly allocated 1:1 to pembrolizumab 200 mg or placebo IV every 3 weeks in combination with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 IV on days 1 and 8 of every 3-week cycle. Pembrolizumab will be continued for ≤35 cycles or until progression, unacceptable toxicity, or withdrawal. Gemcitabine will be continued until progression, unacceptable toxicity, or withdrawal. Cisplatin will be given for a maximum of 8 cycles. Primary endpoints are progression-free survival and overall survival. Secondary endpoints are objective response rate, duration of response, and safety. Exploratory endpoints include disease control rate and health-related quality of life. Tumor imaging by CT or MRI will be performed every 6 weeks until week 54, and every 12 weeks thereafter. Adverse events will be monitored throughout the study and graded according to NCI CTCAE v.5.0. Recruitment began in September 2019 and is underway in 19 countries.
Clinical trial identification
NCT04003636.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp.
Legal entity responsible for the study
Merck Sharp & Dohme Corp.
Funding
Merck Sharp & Dohme Corp.
Disclosure
J.W. Valle: Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Ltd; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nucana; Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Agios; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: GenoScience Pharma; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyt; Advisory/Consultancy: Merck; Advisory/Consultancy: Mundipharma EDO; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Pieris Pharmaceuticals; Advisory/Consultancy: QED; Advisory/Consultancy: Wren Laboratories; Advisory/Consultancy: Servier. R.K. Kelley: Advisory/Consultancy, Payments to self (advisory board): Genentech/Roche; Advisory/Consultancy, Payments to self (advisory board): Gilead; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: Agios; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: BMS; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: Merck; Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Partner Therapeutics; Research grant/Funding (institution): QED; Research grant/Funding (institution): Taiho. J. Furuse: Honoraria (self): Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin pharma, Shionogi, EA pharma, Eli Lilly Japan, Takeda, Chugai Pharma, Fujifilm, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobel p; Research grant/Funding (institution): Eisai, Fujifilm, Ono Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly Japan, Astellas Pharma, AstraZeneca, Abbvie, Shire, Merck Serono, Takara Bio, Chugai Pharma, Bayer Yakuhin, Otsuka, Novartis, MSD, Sumitomo Dainippon, J-Pharma. J. Edeline: Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: BTG; Research grant/Funding (self): Beigene; Travel/Accommodation/Expenses: Amgen. R.S. Finn: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Exelixis; Advisory/Consultancy: C Stone Pharma. Z. Ren: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck. S-C. Su: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. U. Malhotra: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. A.B. Siegel: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. A. Vogel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Sanofi; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self): Decalth Systems; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self): Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Baxalta; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: BTG.