Verastem announces preliminary avutometinib and sotorasib data

Verastem (VSTM) announced preliminary clinical data for the triplet combination of avutometinib and sotorasib plus defactinib in the RAMP 203 Phase 1/2 study in KRAS G12C mutant advanced non-small cell lung cancer, or NSCLC. No dose-limiting toxicities, or DLTs, have been observed in the triplet combination. RAMP 203 continues to progress, with additional enrollment expected and an interim update is planned to be presented at a medical meeting in the second half of 2025. As of a November 21, data cutoff, three patients whose cancer previously progressed on a G12C inhibitor have been treated with the triplet combination of sotorasib 960 mg administered daily on a continuous schedule and avutometinib 3.2 mg twice-weekly, or BIW, plus defactinib 200 mg twice-daily, or BID. Avutometinib and defactinib are administered on a three out of four weeks schedule. Two of the three patients demonstrated initial tumor reductions of at least 20% at the first scan. As of the data cutoff, all three patients remain on treatment. With no DLTs observed in the first triplet combination cohort, the company anticipates the enrollment of additional patients to the triplet combination prior to presenting the data at a medical meeting next year. As previously reported, the doublet combination of avutometinib with sotorasib has completed enrollment in the G12C inhibitor treatment-naive Stage 1 Part B cohort. The KRAS G12C inhibitor prior-treated Stage I Part B cohort is still enrolling patients and is anticipated to complete enrollment in early 2025. Patients in both cohorts continue to be followed for safety and efficacy to determine if observed efficacy supports expanded enrollment. The company plans to complete enrollment and evaluate the safety and efficacy of the triplet combination, before expanding either of the doublet cohorts.