On November 22, 2021 Mirati Therapeutics, Inc. (Nasdaq:MRTX), a clinical-stage targeted oncology company and Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported a non-exclusive clinical collaboration agreement to evaluate the combination of Mirati’s investigational KRASG12C inhibitor adagrasib with Verastem Oncology’s investigational RAF/MEK inhibitor VS-6766 in KRASG12C-mutant non-small cell lung cancer (NSCLC) (Press release, Mirati, NOV 22, 2021, Mirati Therapeutics and Verastem Oncology Partner to Evaluate Adagrasib in Combination with VS-6766 in KRASG12C-Mutant Non-Small Cell Lung Cancer [SID1234595913]).

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Verastem Oncology

The primary objective of this multi-center, single-arm, open-label Phase 1/2 trial is to determine the maximum tolerated dose and recommended Phase 2 dose for the combination of adagrasib and VS-6766 in patients with KRASG12C-mutant NSCLC. The study will also investigate the safety, tolerability and efficacy of the combination in patients who have progressed on a KRASG12C inhibitor. The trial will build on preclinical data showing deeper blockade of ERK pathway signaling resulting in enhanced anti-tumor efficacy with the combination of adagrasib and VS-6766 relative to either agent alone.

"We are pleased to collaborate with Verastem Oncology on this clinical study of VS-6766 and adagrasib. We believe the data from this trial will help to better understand how these agents, when combined, could help improve patient outcomes," said James Christensen, Ph.D., chief scientific officer, 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 its expanding development portfolio to benefit people living with difficult-to-treat cancers."

"We continue to see evidence of the differentiated potential of the dual RAF and MEK properties and favorable safety profile of VS-6766 as an ideal combination therapy in treating RAS pathway-driven cancers. We are excited to partner with Mirati Therapeutics as part of our focused and rapidly advancing development strategy," said Brian Stuglik, CEO of Verastem Oncology. "Specifically, this collaboration will provide data on the potential of VS-6766 with adagrasib to provide deeper and more durable responses in patients with KRASG12C-mutant NSCLC by overcoming downstream resistance mechanisms in the RAS pathway to address unmet needs for NSCLC patients with KRASG12C mutations."

Under the terms of the agreement, Verastem Oncology and Mirati will have joint oversight of the study.

About KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

Approximately 85% of lung cancers are non-small cell lung cancer (NSCLC), which are the single leading cause of cancer deaths worldwide.1 KRAS mutation occurs in approximately 25% of NSCLC adenocarcinoma patients.2 Two of the most common types of KRAS mutations are G12C, which occurs in approximately 14% of patients with NSCLC adenocarcinoma, as well as G12V, which is present in approximately 7% of NSCLC adenocarcinoma.3,4 Currently, there is a high unmet need in the second-line treatment of KRAS mutant NSCLC.1,5

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 single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and other solid tumors with KRASG12C mutations. Adagrasib is a 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 VS-6766

VS-6766 (formerly known as CH5126766 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK inhibitor VS-6766, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.6

Verastem Oncology has initiated Phase 2 registration-directed trials of VS-6766 with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS-G12V mutant NSCLC as part of its RAMP (Raf And Mek Program) clinical trials.