Press Release<< Back
Mirati Therapeutics and Verastem Oncology Partner to Evaluate Adagrasib in Combination with VS-6766 in KRASG12C-Mutant Non-Small Cell Lung Cancer
Clinical Collaboration to Support the Combination of KRASG12C Inhibitor Adagrasib with RAF/MEK Inhibitor VS-6766 to Establish Triple Blockade of the RAS Signaling Pathway
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
“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
Under the terms of the agreement, Verastem Oncology and Mirati will have joint oversight of the study.
About KRAS Mutant Non-Small Cell
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.
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
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.
About Verastem Oncology
This press release contains forward-looking statements regarding the business of
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
Verastem Oncology Forward-Looking Statements Notice
This press release includes forward-looking statements about Verastem Oncology’s strategy, future plans and prospects, including statements related to the potential clinical value of VS-6766 with adagrasib. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," “can,” “promising” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement.
Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including defactinib or adagrasib in combination with VS-6766; the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis or result in unmanageable safety profiles as compared to their levels of efficacy; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take longer than expected; that our product candidates will experience manufacturing or supply interruptions or failures; that we will be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that the development and commercialization of our product candidates will take longer or cost more than planned; that we,
Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended
1 Molina, Julian R., Non–Small Cell
2 Roman, Marta, et al. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target. Molecular Cancer. 2018;17:33.
3 TCGA PanCancer Atlas (cBioPortal analysis).
5 Pakkala S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insights. 2018;3:3120858
6 Verastem Oncology Press Release. Verastem Oncology Receives Breakthrough Therapy Designation for VS-6766 with Defactinib in Recurrent Low-Grade Serous Ovarian Cancer.
Vice President, Corporate Development
Source: Verastem Oncology