- First clinical study to evaluate novel combination blocking KRAS G12C and its activator SOS1 to potentially increase the therapeutic benefit for lung and colorectal cancer patients
- Study is based on preclinical evidence suggesting synergistic effect of KRAS G12C and SOS1 inhibition
Boehringer Ingelheim and Mirati Therapeutics, Inc. (NASDAQ: MRTX) today announced a clinical collaboration to evaluate the combination of BI 1701963, a SOS1::pan-KRAS inhibitor blocking KRAS independent of mutation type, and MRTX849, a KRAS G12C selective inhibitor in patients with solid tumors that harbor the KRAS G12C mutation. The collaboration will investigate the potential of this combination to provide more effective and durable responses for patients with lung and colorectal cancers who currently have limited treatment options.
Preclinical data suggest that the combination of a KRAS G12C inhibitor with a SOS1::pan-KRAS inhibitor results in increased anti-tumor activity based on the complementary mechanisms of these targeted oncology agents. By shifting the equilibrium from active KRAS(ON) towards the inactive KRAS(OFF) form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C mutant tumors to covalent KRAS G12C inhibitors that bind to KRAS(OFF).
“We look forward to collaborating with Boehringer Ingelheim to test this combination in clinical trials,” said Joseph Leveque, M.D., Executive Vice President and Chief Medical Officer of Mirati Therapeutics, Inc. “This collaboration is aligned with the broad and aggressive development strategy we have for MRTX849 and brings the potential for another therapeutic option to patients with KRAS G12C mutations.”
“We are excited to partner with Mirati in our ambition to make a difference for people living with KRAS-driven cancers. Combining our SOS1::pan-KRAS inhibitor with the mutation specific G12C inhibitor could be a win-win approach enhancing the response to therapy,” said Victoria Zazulina, M.D., Global Medical Head for Oncology at Boehringer Ingelheim. “We have a comprehensive KRAS program including the first SOS1::pan-KRAS inhibitor in the clinic, BI 1701963, for which we are exploring several combinations to optimize its therapeutic benefit in broad patient populations.”
Under the terms of the non-exclusive collaboration, Mirati will be the sponsor of the trial and Boehringer Ingelheim and Mirati will jointly share the costs of and oversee clinical development for the combined therapy.
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 non-small cell lung cancer (NSCLC) adenocarcinoma patients, in 3-4% of colorectal cancer patients, and in 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 and in the first quarter of 2020, enrollment began in the registration enabling cohort in monotherapy NSCLC, colorectal cancer and pancreatic cancer.
About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that is designed to bind to the catalytic domain of SOS1 preventing the interaction with KRAS(OFF) and simultaneously blocking SOS1 driven feedback. This reduces the formation of KRAS(ON) and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as recently published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR). BI 1701963 is currently being evaluated in a Phase I clinical trial in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors.
Forward Looking Statements
This press release contains forward-looking statements regarding the business of Mirati Therapeutics, Inc. (“Mirati”). Any statement describing Mirati’s goals, expectations, financial or other projections, intentions or beliefs, development plans and the commercial potential of Mirati’s drug development pipeline, including without limitation MRTX849, sitravatinib and MRTX1133, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to risks and uncertainties, particularly those challenges inherent in the process of discovering, developing and commercialization of new drug products that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.
Mirati’s forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati’s forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati’s programs are described in additional detail in Mirati’s quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the U.S. Securities and Exchange Commission (the “SEC”) available at the SEC’s Internet site (www.sec.gov).These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.
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