|TARGETS:||Receptor tyrosine kinases (RTKs) implicated in suppressing the immune response to tumors, including TAM family receptors (TYRO3, Axl, Mer) and split family receptors (VEGFR2, KIT).|
|INDICATIONS:||Sitravatinib in combination with Checkpoint Inhibitor therapy:
Sitravatinib as a single agent:
|STATUS:||Mirati sponsored combination trials:
Mirati sponsored single agent trials:
Mechanism of Action Studies:
Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO®), an anti-PD-1 checkpoint inhibitor, in patients whose cancers have progressed despite treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.
Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion clinical trial emphasizing enrollment of patients whose tumors harbor specific mutations in the CBL protein. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma. Sitravatinib potently inhibits these RTKs and is being investigated as a treatment option for cancer patients with CBL mutations.
As part of a strategic alliance with BeiGene, sitravatinib is also being tested in a number of additional clinical trials in China and Australia.
Sitravatinib (MGCD516) Publications
ASCO Genitourinary Cancers Symposium
World Conference on Lung Cancer 2017
Click to view “Evidence of Clinical Activity of Sitravatinib in Combination with Nivolumab in NSCLC Patients Progressing on Prior Checkpoint Inhibitor Therapy”
Click to view “CBL Mutations as Potential Mediators of EGFR TKI Resistance Effectively Treated with Sitravatinib”
IASLC 2017 CHICAGO
IASLC 2016 TiP Poster #4109
IASLC 2016 TiP Poster #4795
ASCO 2016 Poster #2575