Sitravatinib Plus Nivolumab Fails to Meet OS End Point in Nonsquamous NSCLC

The combination of sitravatinib (MGCD516) and nivolumab (Opdivo) did not meet the primary end point of overall survival (OS) compared with docetaxel as second- or third-line treatment for patients with advanced nonsquamous non–small cell lung cancer (NSCLC) who progressed on prior chemotherapy and immune checkpoint inhibitor therapy in the phase 3 SAPPHIRE trial (NCT03906071).¹

Patients in the experimental arm will be allowed to continue therapy if they are experiencing clinical benefit and want to remain on treatment. Full study results will be published in the future.

“Mirati extends gratitude to the patients who participated in this clinical trial, their loved ones, and the trial investigators, without whom important work like this would not have been possible,” Alan Sandler, MD, chief medical officer of Mirati Therapeutics, stated in a news release. “As we move forward, we are optimistic about our ability to positively impact the lives of patients living with cancer through the advancement of our broad and differentiated pipeline of targeted oncology programs.”

Sitravatinib is an investigational spectrum-selective kinase inhibitor designed to potently inhibit receptor tyrosine kinases, including the TAM family receptors TYRO3, Axl, and Mer; the split family receptors VEGFR2 and KIT; and RET.

The open-label, randomized trial enrolled patients with nonsquamous NSCLC who received at least 1 but no more than 2 prior treatment regimens in the advanced setting.² Prior treatment with chemotherapy and an immune checkpoint inhibitor, either in combination or sequenced, was required. A checkpoint inhibitor needed to be included in patients’ last treatment regimen, and radiographic disease progression on or after treatment was required. Patients also had to be candidates for docetaxel in the second- or third-line setting.

Key exclusion criteria included uncontrolled brain metastases, tumors harboring EGFR, ROS1, or ALK mutations or ALK fusions, unacceptable toxicity with a prior checkpoint inhibitor, and any systemic therapy following checkpoint inhibitor therapy, other than maintenance chemotherapy.

Patients were randomly assigned to receive nivolumab at 240 mg every 2 weeks or 480 mg every 4 weeks plus oral sitravatinib once per day, or 75 mg/m² of intravenous docetaxel infused over 1 hour every 3 weeks.

Along with the primary end point of OS, safety, objective response rate, and progression-free survival served as secondary end points.

References

1. Mirati Therapeutics provides update on the phase 3 SAPPHIRE study evaluating sitravatinib in combination with Opdivo. News release. Mirati Therapeutics. May 24, 2023. Accessed May 25, 2023. https://ir.mirati.com/press-releases/press-release-details/2023/
2. Phase 3 study of sitravatinib plus nivolumab vs docetaxel in patients with advanced non-squamous non-small cell lung cancer (SAPPHIRE). ClinicalTrials.gov. Updated May 6, 2022. Accessed May 25, 2023. https://clinicaltrials.gov/ct2/show/NCT03906071