Abstract CT283: KEYNOTE-966: A randomized, double-blind, placebo-controlled, phase 3 study of pembrolizumab in combination with gemcitabine and cisplatin for the treatment of advanced biliary tract carcinoma
Authors: Finn Richard S. , Kelley Robin K. , Furuse Junji , Edeline Julien , Ren Zhenggang , Su Shu-Chih , Malhotra Usha , Siegel Abby B. , Valle Juan W. 
Published: September 2020

Background: Biliary tract cancer (BTC), including intra- or extrahepatic cholangiocarcinoma (CCA) and gallbladder cancer, is an aggressive malignancy with limited treatment options. Most patients (pts) present with advanced or unresectable disease, for which the current first-line standard of care is gemcitabine with cisplatin. Prognosis for these pts is poor, with median survival of approximately 12 months. Pembrolizumab (pembro) has improved outcomes when combined with platinum-based chemotherapy in other tumor types (eg, gastric/GEJ, NSCLC). The randomized, placebo-controlled, double-blind, phase 3 KEYNOTE-966 trial (NCT04003636) will be conducted to evaluate pembro plus gemcitabine and cisplatin compared with placebo plus gemcitabine and cisplatin in pts with metastatic or unresectable locally advanced BTC. Methods: Pts will be randomly assigned 1:1 to receive pembro 200 mg or placebo IV every 3 weeks plus gemcitabine 1000 mg/m2 IV and cisplatin 25 mg/m2 IV on days 1 and 8 of every 3-week cycle. Cisplatin will be given for a maximum of 8 cycles. Treatment with pembro/placebo will continue for up to 35 administrations or until disease progression, unacceptable toxicity, or withdrawal from the study. Gemcitabine will be continued until disease progression, unacceptable toxicity, or withdrawal from the study. Pts will be stratified by region (Asia, non-Asia), stage (locally advanced, metastatic), and site of origin (gallbladder, intrahepatic CCA, or extrahepatic CCA). Key eligibility criteria are age ≥18 years; histologically confirmed metastatic or unresectable locally advanced BTC, measurable by RECIST v1.1; no prior systemic therapy for advanced BTC; Eastern Cooperative Oncology Group performance status of 0 or 1; and tumor sample adequate for biomarker analyses. Pts with past or ongoing hepatitis C or controlled hepatitis B virus infection are eligible per protocol-defined criteria. During the initial stage, response will be assessed by imaging every 6 weeks until week 54 and every 12 weeks thereafter. Safety, assessed by CTCAE v.5.0, will be monitored throughout the study and for 30 days after treatment end or 90 days for serious adverse events. The primary end points are progression-free survival (as assessed by blinded independent central review) and overall survival (OS). Secondary end points are objective response rate, duration of response, and safety. Additional analyses will include disease control rate, health-related quality of life (by EORTC QLQ-C30, EuroQol EQ-5D, and EORTC QLQ-BIL21), and molecular and genetic biomarkers. The study opened to recruitment on September 24, 2019. Recruitment is underway in 17 countries and will continue until approximately 788 pts are enrolled.

Citation Format: Richard S. Finn, Robin K. Kelley, Junji Furuse, Julien Edeline, Zhenggang Ren, Shu-Chih Su, Usha Malhotra, Abby B. Siegel, Juan W. Valle. KEYNOTE-966: A randomized, double-blind, placebo-controlled, phase 3 study of pembrolizumab in combination with gemcitabine and cisplatin for the treatment of advanced biliary tract carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT283.