Mirati's sitravatinib yet to improve survival at interim phase 3 cancer review, pushing back approval plan

Mirati Therapeutics is going to have to wait a bit longer to learn whether sitravatinib works. Having touted an interim phase 3 review as an event that could support full approval, the biotech has learned the lung cancer study will continue to its final analysis.

Last month, Charles Baum, M.D., Ph.D., head of R&D at Mirati, told investors the interim analysis could support filings for approval of the multi kinase inhibitor in the U.S. and Europe by the middle of next year. Instead, the trial will continue to its final analysis, which is also scheduled for around the middle of next year, setting back Mirati’s plans to bring the drug to market. 

“We remain committed to developing our portfolio of oncology candidates and advancing our lung cancer strategy to positively impact the lives of patients with cancer. We look forward to providing an update based on the full analysis of the SAPPHIRE study in mid-2023,” Baum said in a release Dec. 2.

SAPPHIRE is testing sitravatinib in combination with Bristol Myers Squibb’s checkpoint inhibitor Opdivo. Investigators have randomized 532 second- and third-line non-small cell lung cancer patients to receive the combination or the chemotherapy medication docetaxel. The participants previously benefited from treatment with a checkpoint inhibitor and chemotherapy but then progressed.

Mirati powered the study for a 3.5-month overall survival benefit. In a 68-subject phase 2 clinical trial, median overall survival in recipients of the sitravatinib-Opdivo combination was 14.9 months. One-third of participants were alive after 24 months. Median overall survival in CheckMate 057, a study of Opdivo in a similar setting, was 12.2 months in the checkpoint inhibitor cohort and 9.4 months on docetaxel. 

Baum and his colleagues advanced sitravatinib through the clinic in the belief it may restore the immune response by inhibiting TYRO3, AXL, MER and VEGFR2. The mechanism of action could reduce regulatory T cells and myeloid-derived suppressor cells, release the brakes for expansion of CD8+ T cells, increase natural killer cell response and otherwise enhance the immune response to checkpoint inhibitors.  

If the final analysis shows sitravatinib works as hoped, Mirati could bolster its commercial drug portfolio with a molecule against a disease that affects around 70,000 patients in the U.S. and EU. The biotech sees sitravatinib as a highly synergistic commercial opportunity with its highest-profile asset, the near-approval KRASG12C inhibitor adagrasib.