NCT04727996

Phase II Study of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Biliary Tract Cancer

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Seoul National University Hospital · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

This is open-label, phase II study enrolling advanced BTC patients who have failed to 1st-line chemotherapy.

Detailed description

\<Study Objectives\> Primary Objectives: To characterize the efficacy of Sitravatinib and Tislelizumab combination in biliary tract cancer patients who have failed to 1st-line chemotherapy but no more than 2 lines of prior chemotherapy regimen Secondary Objectives: To see the safety of Sitravatinib and Tislelizumab combination in biliary tract cancer patients who have failed to 1st-line chemotherapy \<Rationale\> sitravatinib and tislelizumab may elicit greater antitumor activity, as sitravatinib is predicted to enhance several steps in the cancer immunity Cycle that may augment the efficacy of tislelizumab. First, the antitumor activity of sitravatinib may promote the release of tumor antigens. Second, inhibition of the split kinase receptors VEGFR-2 and KIT may decrease the number of Tregs and MDSCs, thus promoting the expansion and migration of antitumor cytotoxic T cells, and their infiltration into tumor tissue. Third, sitravatinib may reverse the immunosuppressive effects within the tumor microenvironment that are mediated by the TAM receptors through inhibition of MERTK, resulting in an increased number of M1- versus M2-polarized macrophages and release of IL 12, IL-6, and TNF. These downstream effects enhance CD8+ T-cell activation, and through the inhibition of AXL, promote increased antigen presentation through termination of the Toll-like receptor dependent inflammatory response in dendritic cells. In biliary tract cancer, this sitravatinib and tislelizumab combination has not been tested so far. In this protocol, we will test sitravatinib and tislelizumab combination in advanced biliary tract cancer. \<hypothesis\> Selective receptor tyrosine kinases inhibit key molecular and cellular pathways strongly implicated in checkpoint inhibitor resistance and therefore represent reasonable strategies to enhance or restore antitumor immunity when combined with anti-PD-1 or anti-PD-L1 monoclonal antibodies. \<Study design\> This is open-label, phase II study enrolling advanced BTC patients who have failed to 1st-line chemotherapy. All patients will receive sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent.

Conditions

• Advanced Biliary Tract Cancer

Interventions

Type	Name	Description
DRUG	Sitravatinib	120 mg will be administered orally once daily
DRUG	Tislelizumab	200 mg will be administered intravenously (IV) once every 3 weeks

Timeline

• Start date: 2020-11-01
• Primary completion: 2023-07-31
• Completion: 2024-12-31
• First posted: 2021-01-27
• Last updated: 2024-04-19

Locations

1 site across 1 country: South Korea