Revolution Medicines Updates RMC-6236 Monotherapy Data in Advanced Pancreatic Ductal Adenocarcinoma

On October 23, 2024, Revolution Medicines, Inc., a clinical-stage oncology company listed on Nasdaq under the ticker RVMD, announced promising data regarding their RAS(ON) multi-selective inhibitor, RMC-6236, for treating pancreatic ductal adenocarcinoma (PDAC) in patients who have undergone previous treatments. The announcement was made during a late-breaking poster session at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics held in Barcelona from October 23-25, 2024.

Dr. Mark A. Goldsmith, CEO and Chairman of Revolution Medicines, highlighted the significance of the updated data, emphasizing the strong progression-free survival (PFS) and overall survival (OS) rates observed in patients treated with RMC-6236 in the Phase 1 study. The data supports the ongoing Phase 3 registrational study, RASolute 302, and suggests that RMC-6236 monotherapy could become a crucial treatment option for advanced or metastatic pancreatic cancer patients.

The Phase 1/1b study, RMC-6236-001, is a multicenter, open-label, dose-escalation and dose-expansion study aimed at evaluating the efficacy of RMC-6236 as a monotherapy in patients with advanced solid tumors bearing RAS mutations or wild-type RAS. By the data cutoff date on July 23, 2024, 127 patients with previously treated PDAC were administered RMC-6236 at doses ranging from 160 mg to 300 mg once daily.

The inhibitor was generally well tolerated across the specified doses, with a safety profile consistent with previous results and no new safety signals observed. The most frequently reported treatment-related adverse events (TRAEs) included rash and gastrointestinal-related toxicities, mostly at Grade 1 or 2 severity. Grade ≥3 TRAEs included rash (8%), stomatitis (3%), and diarrhea (2%). Dose modifications due to TRAEs occurred in 35% of patients, but no patients discontinued treatment because of these adverse events. The average dose intensity achieved was 92%.

RMC-6236 showed durable antitumor activity with updated PFS and OS data. Patients with PDAC bearing a KRAS G12X mutation in the second-line setting achieved a median PFS of 8.5 months and a median OS of 14.5 months. For patients with any RAS mutation in the second-line setting, median PFS was 7.6 months, and median OS was 14.5 months. At six months, the landmark OS for patients with KRAS G12X mutation was 89%, and for those with any RAS mutation, it was 91%. The objective response rate for tumors with KRAS G12X mutations was 29% in the second-line group and 22% in the third-line and beyond group. The disease control rate was 91% and 89% respectively for these groups.

Dr. Brian M. Wolpin, Principal Investigator for the RMC-6236-001 study and lead author of the ENA presentation, stressed the high unmet medical need in pancreatic cancer, noting that it is the most RAS-mutated major cancer, with over 90% of patients having tumors with RAS mutations. Dr. Wolpin expressed excitement over the clinical activity observed at tolerable doses in the Phase 1 study, offering hope for patients facing this challenging disease.