Mirati Therapeutics announced a clinical collaboration agreement with Novartis to evaluate the combination of MRTX849, Mirati's investigational KRAS G12C inhibitor and TNO155, Novartis' investigational SHP2 inhibitor, in patients with advanced solid tumors that harbor KRAS G12C mutations.

SHP2 is an important mediator of cellular signaling through the RAS/MAP kinase pathway and is frequently overactive in various types of cancer. Preclinical data has shown that the combination of a KRAS G12C inhibitor with a SHP2 inhibitor results in increased anti-tumor activity based on their complementary mechanisms of action.

"In our non-clinical studies, the combination of MRTX849 with a SHP2 inhibitor demonstrated a clear impact on KRAS signaling and resulted in a significant increase in anti-tumor activity in some tumors versus either investigational drug alone," said James Christensen, Ph.D., Executive Vice President and Chief Scientific Officer, Mirati Therapeutics. "We believe this collaboration will strengthen and broaden our KRAS program, potentially increasing the efficacy of MRTX849 and bringing another option to patients with KRAS G12C mutations who have traditionally exhibited resistance with other therapies." 

Under terms of the non-exclusive collaboration, Mirati will sponsor the trial and Novartis and Mirati will jointly oversee and share the costs of clinical development activities for the combined therapy. Novartis will provide TNO155 at no cost.

MRTX849 is an investigational, orally-available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients, 4% of colorectal cancer patients, and subsets of other types of cancer. 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. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly-identified, KRAS G12C-positive advanced solid tumors.

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