On October 12, 2022 Mirati Therapeutics, Inc. (Nasdaq: MRTX), a clinical-stage targeted oncology company, and Aadi Bioscience, Inc. (Nasdaq: AADI), a commercial stage biopharmaceutical company focused on developing and commercializing precision therapies for genetically defined cancers with alterations in mTOR pathway genes, reported a clinical collaboration to evaluate the combination of adagrasib, a KRASG12C selective inhibitor, and nab-sirolimus, a small molecule mTOR inhibitor complexed with human albumin in KRAS G12C mutant non-small cell lung cancer (NSCLC) and other solid tumors (Press release, Mirati, OCT 12, 2022, View Source [SID1234621962]).

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The primary objective of this multi-center, single-arm, open-label Phase 1/2 trial is to determine the optimal dose and recommended Phase 2 dose for the combination of adagrasib and nab-sirolimus in patients with KRASG12C – mutant solid tumors. In addition, the study will investigate the safety, tolerability and efficacy of adagrasib and nab-sirolimus in combination in patients both with and without prior exposure to a KRASG12C inhibitor. The trial will build on preclinical data showing enhanced anti-tumor efficacy with the combination of adagrasib and nab-sirolimus relative to either agent alone.

"We are pleased to collaborate with Aadi on this clinical study of adagrasib and nab-sirolimus. Our collaborative preclinical work has demonstrated that combinatorial mTOR and KRAS inhibition addresses key bypass and feedback pathways associated with either drug target and also results in enhanced efficacy in tumor models harboring KRASG12C mutations. We believe the data from this trial may improve patient outcomes," said Charles Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "This clinical collaboration is an example of how Mirati is aggressively advancing the study of adagrasib both as a monotherapy and in rational combinations as part of our expanding development portfolio to benefit people living with difficult-to-treat cancers."

"KRAS and mTOR are closely linked and key pathways in oncogenesis and resistance to treatment. This collaboration builds on strong preclinical and mechanistic rationale supporting the combination of the two drugs to potentially provide greater benefit for patients with KRASG12C mutant NSCLC and other cancers," said Neil Desai, Ph.D., founder, president and chief executive officer, Aadi Bioscience, Inc. "We look forward to working closely with our Mirati counterparts to bring this treatment to those in need."

Under the terms of the collaboration agreement, Mirati will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Aadi, will oversee and share the cost 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. Studies of adagrasib have shown that the drug has a long half-life, extensive tissue distribution and is well tolerated. Adagrasib has also shown, in clinical trials, CNS penetrance and single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors with KRASG12C mutations. Adagrasib is being evaluated in several clinical trials in combination with other anti-cancer therapies with strong scientific rationale in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science.

About nab-sirolimus
Nab-sirolimus is a novel albumin-bound nanoparticle form of the mTOR inhibitor sirolimus and is currently being evaluated in a tumor-agnostic registration-directed trial in mTOR inhibitor-naïve malignant solid tumors harboring TSC1 or TSC2 inactivating alterations. In November 2021, nab-sirolimus was approved by the U.S. Food and Drug Administration (FDA) as FYARRO for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).