University of Wisconsin, Carbone Cancer Center, Madison, WI
John Ebben , Jens C. Eickhoff , Dustin A. Deming , Howard S. Hochster , Anita Ahmed Turk , Vaibhav Sahai , Nataliya Volodymyrivna Uboha
Background: Despite recent approvals of immune checkpoint inhibitors with chemotherapy in the first-line setting, the median overall survival (mOS) for patients with advanced biliary tract cancer (BTC) remains less than 15 months. CD73 is a key enzyme responsible for the conversion of extracellular adenosine 5’-monophosphate into adenosine and may play an important role in creating an immunosuppressed tumor microenvironment. High expression of CD73 in BTC is associated with decreased OS. Quemliclustat (Q) is a potent, selective, reversible inhibitor of CD73. Q in combination with chemotherapy has demonstrated promising activity in patients with advanced pancreatic cancer without significant increase in adverse events. The BTCRC-GI22-564 study evaluates safety and preliminary efficacy of Q in combination with zimberelimab (Z), a monoclonal antibody targeting human PD-1, with gemcitabine and cisplatin (GC) as first-line therapy for patients with advanced BTC, QUIC (Q and Immunotherapy in Cholangiocarcinoma). Methods: This is an open label, single arm, phase II multi-site trial, evaluating Q and Z in combination with GC in patients with advanced BTC who have not received systemic treatment for advanced disease or who completed adjuvant therapy > 6 months prior to development of recurrent disease. Chemotherapy is given on days 1, 8, 22 and 29 of each 42-day cycle as per local standards. Z is administered at a fixed dose of 360 mg via IV infusion every 3 weeks. Q is administered via IV infusion on days 1, 15, and 29. A safety run-in portion built into the study is planned to enroll 6 subjects to ensure there are no dose limiting toxicities (DLT). If a study defined DLT is observed, Q, gemcitabine and cisplatin will be reduced by 1 dose level, and an additional 6 subjects will be enrolled in the safety run-in portion. The primary efficacy endpoint is median progression free survival (mPFS) with null and alternative survival of 6.0 and 10.0 months, respectively. Based on an accrual rate of 3 patients per month, we expect to accrue 33-39 patients which will provide at least 83% power with a one-sided alpha of 0.1. Secondary endpoints include mOS, disease control rate, overall response rate, and duration of response. Correlative endpoints will assess clinical outcomes with immune infiltration within tumor microenvironment, CD73 and PD-L1 expression. The QUIC study is currently open to enrollment through BTCRC. Clinical trial information: NCT06048133.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Jia Fan
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Richard D. Kim
2023 ASCO Annual Meeting
First Author: Li Jingjing
2023 ASCO Annual Meeting
First Author: Zhen-gang Yuan