Ignite Creation Date:
2024-05-06 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 1:55 PM
Study NCT ID:
NCT04727996
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-19
First Post:
2021-01-23
Brief Title:
Phase II Study of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Biliary Tract Cancer
Sponsor:
Seoul National University Hospital
Organization:
Seoul National University Hospital
Study Overview
Official Title:
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
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BTC-BGB
Brief 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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None