On September 20, 2021 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported a clinical collaboration agreement with Amgen to evaluate the combination of VS-6766, Verastem Oncology’s investigational dual RAF/MEK inhibitor, with Amgen’s KRAS G12C inhibitor LUMAKRASTM (sotorasib) in KRAS G12C-mutant non-small cell lung cancer (NSCLC) (Press release, Verastem, SEP 20, 2021, View Source [SID1234588006]).

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The Phase 1/2 trial will evaluate the safety, tolerability and efficacy of VS-6766 in combination with LUMAKRASTM in patients with KRAS G12C-mutant NSCLC who have not been previously treated with a KRAS G12C inhibitor as well as in patients who have progressed on a KRAS G12C inhibitor. The study will therefore investigate the potential benefits of a more complete vertical blockade of the RAS pathway with the combination of VS-6766 (RAF/MEK blockade) with LUMAKRASTM (G12C inhibition) in KRAS G12C-mutant locally advanced or metastatic NSCLC.

"Recent data indicate that acquired resistance to KRAS G12C inhibitors in patients occurs predominantly through additional mutations in the RAS pathway, many of which may be addressed with a downstream inhibitor such as VS-6766,"1 said Ramaswamy Govindan, M.D., Professor, Department of Medicine, Oncology Division at Washington University School of Medicine and lead investigator of the study. "This clinical study of VS-6766 and LUMAKRASTM will build on preclinical data showing synergy between these two agents, including tumor regression through deeper blockade of ERK pathway signaling."2

"We are pleased to partner with Amgen on this important research that could potentially expand treatment options for patients with KRAS G12C-mutant NSCLC," said Brian Stuglik, CEO of Verastem Oncology. "This collaboration advances our strategy to fully explore the potential of VS-6766 as a backbone of therapy to treat RAS pathway-driven cancers."

Verastem Oncology expects to initiate the clinical trial with VS-6766 and LUMAKRASTM by the end of 2021.

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.3 KRAS mutation occurs in approximately 25% of NSCLC adenocarcinoma patients.4 Two of the most common types of KRAS mutations are G12C, which occurs in approximately 13% of patients with NSCLC adenocarcinoma, as well as G12V, which is present in approximately 7% of NSCLC.5,6 Currently, there is a high unmet need in the second-line treatment of KRAS mutant NSCLC.3,7

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.8

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.