On January 7, 2019, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX) a clinical-stage targeted oncology company, reported a clinical collaboration with Bristol-Myers Squibb Company to evaluate the combination of sitravatinib and nivolumab (OPDIVO), in Mirati’s planned Phase 3 trial in second line non-small cell lung cancer (NSCLC) patients who have progressed following treatment with a platinum-based regimen and a checkpoint inhibitor (Press release, Mirati, JAN 7, 2019, View Source [SID1234532531]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 3 pivotal trial is expected to start in the first half of 2019 and will randomize patients to either the combination of sitravatinib with nivolumab or single-agent docetaxel. The trial will include an interim analysis of overall response rate (ORR) as the basis for potential accelerated approval. This interim analysis and the use of a docetaxel control arm follows guidance from Mirati’s FDA end of phase 2 meeting. The primary endpoint of the final analysis for the Phase 3 clinical trial will be overall survival.

"Our Phase 2 clinical trial of sitravatinib plus nivolumab in patients with checkpoint refractory NSCLC has shown promising activity and a well-tolerated safety profile," said Charles Baum, M.D., Ph.D., President and Chief Executive Officer of Mirati. "The trial is expected to result in a new drug application (NDA) for sitravatinib for the treatment of NSCLC patients whose tumors have progressed following treatment with a platinum containing regimen and a checkpoint inhibitor. This collaboration further validates the potential of sitravatinib and allows Mirati to invest in and expand the development of our clinical and pre-clinical programs."

Under the terms of the collaboration, Mirati will sponsor and fund the clinical trial and Bristol-Myers Squibb will provide nivolumab at no cost. Mirati maintains global development and commercial rights to sitravatinib outside of certain Asian territories, where it is partnered with BeiGene, and is free to develop the program in combination with other agents.

About Sitravatinib

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 who have experienced documented disease progression following 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