Revolution Medicines reports objective response rate in RMC-6236 trial of 38%

Revolution Medicines on Sunday announced anti-tumor and safety data for RMC-6236, its RASMULTI(ON) Inhibitor, in patients with previously treated non-small cell lung cancer and pancreatic ductal adenocarcinoma across several dose levels and KRASG12X genotypes, including common KRAS-mutant genotypes G12D and G12V. These initial results were presented during a Proffered Paper session at the European Society for Medical Oncology Congress in Madrid, October 20-24, 2023. “Today’s presentation marks an important milestone in the clinical development of RMC-6236, an unprecedented, oral RASMULTI(ON) Inhibitor with an innovative mechanism of action. The findings reinforce our belief that by inhibiting the (ON), or active, form of diverse RAS cancer drivers, RMC-6236 can lead to meaningful clinical responses in patients at dose levels that are generally well tolerated,” said Mark A. Goldsmith, M.D., Ph.D., CEO and chairman of Revolution Medicines. The RMC-6236-001 Phase 1/1b trial is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate RMC-6236 as monotherapy in patients with advanced solid tumors harboring KRASG12X mutations. As of an October 12, 2023 data extraction, a total of 111 patients with NSCLC or PDAC were treated at dose levels administered once daily ranging from 80 mg to 400 mg. Common KRAS mutations in patients evaluated included G12D, G12V, G12R, G12A and G12S; patients with KRASG12C mutations were excluded from the study due to the availability of currently approved KRASG12C(OFF) inhibitors. All patients had previously been treated with standard of care appropriate for tumor type and stage. Patients with NSCLC had received a median of two prior lines of therapy while patients with PDAC had received a median of three prior lines of therapy. RMC-6236 demonstrated preliminary evidence of clinical activity and an acceptable safety profile that was generally well tolerated across the dose levels analyzed. Clinical activity was evaluated in patients who had received the first dose of RMC-6236 at least eight weeks prior to the data extraction date. Among the 40 efficacy evaluable NSCLC patients, the objective response rate was 38%, with one patient achieving a complete response as a best response and 14 patients achieving a partial response. The disease control rate in this NSCLC population was 85%. Among the 46 efficacy evaluable PDAC patients, the objective response rate was 20%, with nine patients achieving a PR as a best response. The DCR in this PDAC population was 87%. Confirmed objective responses included tumors harboring KRAS mutations G12D, G12V or G12R, and disease control was observed across all KRAS mutations, including G12A and G12S. Shares of Revolution Medicines are down 43% to $16.06 in late morning trading.