After a five and a half month wait, Mirati Therapeutics finally has the answer it’s been waiting for on a lung cancer med called sitravatinib: The therapy did not improve survival in a phase 3 study.

Back in December 2022, Mirati said that the SAPPHIRE trial would continue to its final analysis instead of getting an interim readout as planned. The company had hoped to use the early data to support an FDA application for approval in second- and third-line non-small cell lung cancer (NSCLC).

Mirati was looking for a 3.5-month overall survival benefit, but, according to a brief update Wednesday afternoon, that measure was not successful at the final analysis. The company is not releasing the data set at this time but promised to do so “at a future date.” Patients who are experiencing clinical benefit may continue on treatment at the discretion of the principal investigators.

The failure marks the end of the road for sitravatinib, a Mirati spokesperson confirmed to Fierce Biotech. The therapy will not be developed by Mirati in any indication at this time, however, Beigene holds the rights to development in Asia, New Zealand and Australia.  

Chief Medical Officer Alan Sandler, M.D., who took over the role in November 2022, pointed to “our broad and differentiated pipeline of targeted oncology programs.” That broad pipeline includes Krazati, the KRAS inhibitor that was approved for KRAS-mutated NSCLC in December 2022.

SAPPHIRE was testing sitravatinib in combination with Bristol Myers Squibb’s checkpoint inhibitor Opdivo against the chemotherapy medication docetaxel. Participants had previously received prior therapy with chemotherapy and immune checkpoint inhibitors but progressed.

Sitravatinib is a spectrum-selective kinase inhibitor that Mirati had hoped would help overcome resistance to checkpoint inhibitors. In a small, 68-patient phase 2, the company previously showed that sitravatinib achieved median overall survival of 14.9 months when combined with Opdivo. 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.

Mirati had intended to file sitravatinib with U.S. and EU regulators by the middle of this year.

The therapy was also being tested in some earlier-stage trials in combination with other checkpoint inhibitors. BeiGene struck the deal with Mirati in 2018 for the rights to sitravatinib in Asia.  

Besides Krazati, sitravatinib is Mirati's most advanced asset. The company is also testing another KRAS inhibitor called MRTX1133 for a different form of the mutation in a phase 1/1b study of patients with pancreatic cancer, colorectal cancer, NSCLC and others.

Reference:https://www.fiercebiotech.com/biotech/miratis-long-wait-next-lung-cancer-med-ends-phase-3-failure