Given that monotherapy with immune checkpoint inhibitors, including the PD-1 inhibitor tislelizumab, has a modest effect in advanced biliary tract cancers, several combination strategies to improve the antitumor activity of immune checkpoint inhibitors are being explored.
Based on preclinical evidence that adding anti-angiogenic agents to immune checkpoint inhibitors induces antitumor immune responses, an open-label, phase 2 study is evaluating the safety and efficacy of the combination of tislelizumab plus the multitargeted angiogenic inhibitor sitravatinib in patients with advanced biliary tract cancer whose disease did not respond to at least 1 systemic therapy.
Do-Youn Oh, MD, PhD, Cancer Research Institute, Seoul National University College of Medicine, South Korea, described the study at the 2022 ASCO GI Cancers Symposium.
An exploratory objective is to assess the relationship between the combination’s efficacy and tumor biomarkers.
Key eligibility criteria include patients with histologically proved biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, and ampulla of Vater cancer, whose disease did not respond to at least 1 previous systemic chemotherapy; have not used ≥2 previous chemotherapy regimens; and have ECOG performance status of 0 or 1.
Patients who have previously received an immune checkpoint inhibitor are eligible to be enrolled. Patients who had unacceptable adverse events during previous immune checkpoint inhibitor treatment will be excluded.
Eligible patients will receive oral sitravatinib 120 mg once daily plus intravenous tislelizumab 200 mg once every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent.
The study’s primary end point is disease control rate; secondary end points are overall response rate, progression-free survival, duration of response, overall survival, and EORTC QLQ-C30, overall adverse events, and immune-related adverse events.
For evaluating the metabolic response, the 18F-FDG PET/CT scan will be performed before treatment and at the first evaluation of response. Tissue biopsies will be conducted at screening, at the first response evaluation, and at disease progression.
The study is currently recruiting patients, with a planned enrollment of 43 patients. Overall, the cohort of patients who have not received a PD-1 or PD-L1 inhibitor will enroll 33 patients, and the cohort of those who have previously received a PD-1 or PD-L1 inhibitor will enroll 10 patients.
Oh DY, Kim JW, Chon H, et al. Phase II study of sitravatinib in combination with tislelizumab in patients with advanced biliary tract cancer who have failed to at least 1 prior systemic treatment: trial in progress. Abstract TPS490.
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