Verastem Oncology Granted Fast Track Designation for Combination of Avutometinib and Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer (NSCLC) - Seite 2

Initial results of the RAMP 203 (NCT05074810) Phase 1/2, multicenter, open label, dose evaluation/expansion study evaluating the efficacy and safety of avutometinib + sotorasib 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 been previously treated with a KRAS G12C inhibitor demonstrated confirmed responses in both KRAS G12C inhibitor resistant and naïve patients. The pharmacokinetic profile of avutometinib in combination with sotorasib in the RAMP 203 trial was similar to results in monotherapy studies. No drug-drug interactions were observed between avutometinib and sotorasib. Avutometinib 4.0 mg PO BIW 21/28 days + sotorasib 960 mg PO QD 28/28 days was selected as RP2D based on dose limiting toxicity (DLT) assessment. These initial RAMP 203 results were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October, 2023. Enrollment of patients with KRAS G12C-mutant NSCLC who are either naïve to or previously treated with a KRAS G12C inhibitor is ongoing in the expansion phase of RAMP 203 with updated results expected in the first half of 2024.

About Avutometinib

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib 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 granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, 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.