On October 7, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported a non-exclusive clinical collaboration agreement with Sanofi to evaluate the combination of adagrasib, the Company’s investigational KRASG12C inhibitor, with Sanofi’s investigational SHP2 inhibitor SAR442720, also known as RMC-4630 (Press release, Mirati, OCT 7, 2021, View Source [SID1234590960]). The Phase 1/2 dose escalation and expansion study will evaluate the combination in patients with previously-treated non-small cell lung cancer (NSCLC) and KRASG12C mutations.
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"Mirati is aggressively advancing a broad adagrasib development program, which includes pursuing novel combination approaches including through this collaboration with Sanofi," said Charles M. Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "There is strong scientific rationale for combining a SHP2 inhibitor with adagrasib, which may help optimize clinical outcomes for patients with KRASG12C-dependent tumors."
SHP2 is upstream of KRAS and mediates cellular signaling through the RAS/MAP kinase pathway and is frequently overactive in various types of cancer. KRASG12C inhibition and SHP2 inhibition have complementary mechanisms of action and have demonstrated additive anti-tumor activity in pre-clinical models.
Under the terms of the agreement, Sanofi will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Mirati, will oversee and share costs of the study.
About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24−48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.
About SAR442720 (RMC-4630)
SAR442720 (RMC-4630) is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by transmitting signals from receptor tyrosine kinases to RAS. SAR442720 (RMC-4630) is the focus of an exclusive global development and commercialization agreement between Sanofi and Revolution Medicines.