Mirati Therapeutics Announces Submission of IND for MRTX849

Mirati Therapeutics has submitted an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to initiate a Phase 1/2 trial with the initial goal to evaluate safety, tolerability and pharmacokinetics of the company's KRAS G12C inhibitor, MRTX849, in patients with advanced solid tumors. The trial will utilize an accelerated titration design with single patient cohorts and intra-patient dose escalation to rapidly achieve an active dose level for MRTX849. Phase 2 expansion cohorts will enroll patients whose tumors are driven by KRAS G12C positive mutations. The Phase 2 portion of the trial in patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) may provide proof of concept and the basis for accelerated approval.

"MRTX849, is a potent, highly selective inhibitor of G12C positive mutations. These mutations occur in large patient populations with NSCLC and CRC tumors, and are also present in patients with other solid tumors, such as pancreatic cancer. We submitted the IND on October 29th, 2018 and plan to begin enrolling patients soon after FDA approval is received. The trial is designed to enable early clinical efficacy data in 2019," said Charles Baum, M.D., Ph.D., President and Chief Executive Officer, Mirati Therapeutics, Inc. "KRAS has long been one of the most difficult targets in all of oncology and this program has the potential to be a breakthrough for patients with G12C positive mutations."

"KRAS has been an elusive target for researchers for more than 30 years. It's exciting to see an IND filing that would potentially provide a therapy for patients with G12C mutations, which were once considered undruggable and who have had no viable treatment options," said Channing J. Der, Ph.D., the Sarah Graham Kenan Professor of Pharmacology at the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center.

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated broad-spectrum tumor regression in a large cohort of KRAS G12C-positive pre-clinical in-vivo human tumor models. MRTX849 demonstrated complete regression of tumors in a subset of models at well-tolerated dose levels. Early proof-of-concept clinical data is anticipated in 2019.