Mirati Announces Clinical Collaboration to Evaluate MRTX849 in Combination with SHP2 Inhibitor TNO155
- Category: Small Molecules
- Published on Wednesday, 10 July 2019 12:09
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SAN DIEGO, CA, USA I July 9, 2019 I Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, today 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.
About Mirati Therapeutics
Mirati Therapeutics (NASDAQ: MRTX) is a San Diego-based clinical-stage biotechnology company dedicated to advancing novel therapeutics that extend the lives of patients by directly addressing the genetic and immunological drivers of cancer. Mirati's lead drug candidate, sitravatinib, is designed to selectively target a spectrum of tyrosine kinases implicated in both tumor growth and the suppression of immune responses to tumors. Sitravatinib has demonstrated durable responses in lung cancer patients whose cancer has progressed despite treatment with checkpoint inhibitors - an area of significant unmet medical need. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including a potentially registration-enabling Phase 3 trial of sitravatinib in non-small cell lung cancer projected to initiate in the first half of 2019. Sitravatinib is also being evaluated as a single agent in patients with NSCLC, melanoma and other solid tumor types whose tumors harbor specific genetic alterations in CBL.
Mirati is also developing novel inhibitors of KRAS mutations including MRTX849, a potent and selective inhibitor of KRAS G12C. This previously difficult to drug target drives approximately 14% of non-small cell lung adenocarcinomas, 4% of colorectal cancer as well as smaller percentages of several other difficult-to-treat cancers. MRTX849 is being evaluated in a Phase 1/2 clinical trial as a treatment for patients with KRAS G12C-positive tumors. Our research on G12C has led to breakthroughs in targeting other KRAS mutations including G12D which drives tumor growth in more patients than G12C and includes pancreatic, colorectal and other types of cancer. For more information, visit www.mirati.com.
SOURCE: Mirati Therapeutics