Mirati had intended that its preliminary findings for sitravatinib would be used to support an FDA application for approval in second and third-line non-small cell lung cancer (NSCLC) but as Mirati was hoping for the 3.5-month overall survival advantage, the metric was not effective in the final analysis.
The data set will not be released at this time but may be released in the future, according to the company. Patients who show clinical benefit may continue to receive therapy at the discretion of the lead investigators.
A Mirati spokeswoman acknowledged that the failure means the end of the road for sitravatinib. Mirati will not develop the medicine, but Beigene has the right to develop it in Asia, New Zealand, and Australia.
The Chief Medical Officer of Mirati, Alan Sandler, emphasized the company’s broad and differentiated pipeline of targeted oncology programs. Krazati, a KRAS inhibitor authorized for KRAS-mutated NSCLC in December 2022, is part of that vast pipeline.
SAPPHIRE was a clinical trial that pitted sitravatinib against the chemotherapeutic drug docetaxel in conjunction with Bristol Myers Squibb’s checkpoint inhibitor Opdivo. Participants had previously undergone chemotherapy and immune checkpoint inhibitors but had progressed.
Sitravatinib is a spectrum-selective kinase inhibitor that Mirati anticipated would assist in overcoming checkpoint inhibitor resistance. In a limited phase 2 trial consisting of a cohort of roughly 68 patients, sitravatinib obtained a median overall survival of 14.9 months when coupled with Opdivo. After 24 months, one-third of the individuals were still alive. The median overall survival in CheckMate 057, a comparable Opdivo trial, was 12.2 months in the checkpoint inhibitor cohort and 9.4 months in the docetaxel cohort.
Mirati had planned to submit sitravatinib to US and European authorities by the middle of this year.
In several earlier-stage trials, the treatment was also evaluated in conjunction with other checkpoint inhibitors. BeiGene agreed to a contract with Mirati in 2018 for the Asian rights to sitravatinib.
Mirati’s most advanced asset, outside of Krazati, is sitravatinib. In phase 1/1b research of patients with pancreatic cancer, colorectal cancer, NSCLC, and other cancers, the firm is also exploring another KRAS inhibitor called MRTX1133 for a different version of the mutation.
