Revolution Medicines Shares Early Data on RMC-9805 Monotherapy for Advanced Pancreatic Cancer

Revolution Medicines, Inc., a clinical-stage oncology firm focused on developing targeted therapies for cancers reliant on RAS mutations, has announced promising initial findings for RMC-9805, a selective inhibitor aimed at the RAS(ON) G12D mutation. This data pertains specifically to patients with previously treated pancreatic ductal adenocarcinoma (PDAC) and was presented at the EORTC-NCI-AACR Symposium on October 25, 2024, in Barcelona.

Mark A. Goldsmith, M.D., Ph.D., the CEO and chairman of Revolution Medicines, highlighted that RMC-9805 has shown initial safety, tolerability, and antitumor activity, evidenced by tumor shrinkage. These early results have reinforced the belief that RMC-9805 could become a significant treatment option for pancreatic cancer patients, either as a standalone therapy or in combination with other treatments. This is the third compound from Revolution Medicines to demonstrate clinical proof-of-concept, underscoring their commitment to advancing novel treatments for cancers with RAS mutations.

The RMC-9805-001 Phase 1/1b clinical trial is a multicenter, open-label study designed to determine the safety and efficacy of RMC-9805 in patients with advanced solid tumors containing the KRAS G12D mutation. As of the data cutoff on September 2, 2024, 179 patients had been treated with various doses of RMC-9805, ranging from 150 mg to 1200 mg once daily and 300 mg to 600 mg twice daily. Patients in the study had undergone a median of two prior treatments, all of which included standard care.

The study results indicated that RMC-9805 has a favorable safety profile and is generally well tolerated across different dosage levels. For those taking 1200 mg daily, the most frequently reported treatment-related adverse events (TRAEs) included gastrointestinal issues like nausea, diarrhea, vomiting, and rash, primarily of Grade 1 severity and usually short-lived. There was one instance of a Grade 3 TRAE (ALT elevation), and no Grade 4 or 5 TRAEs were observed. Four patients experienced TRAEs that necessitated a dose reduction, but no patients discontinued treatment due to TRAEs. No dose-limiting toxicities were found, and the maximum tolerated dose was not reached.

Preliminary efficacy was particularly evaluated in patients with PDAC. At the proposed Phase 2 dose of 1200 mg daily (split between 20 patients taking 1200 mg once daily and 20 patients taking 600 mg twice daily), those who received their first dose at least 14 weeks before the data cutoff achieved an objective response rate of 30%, with a disease control rate of 80%.

David Hong, M.D., of MD Anderson Cancer Center, principal investigator and lead author of the RMC-9805-001 presentation, emphasized that pancreatic cancer, especially the G12D variant, has a notable lack of targeted treatments. The Phase 1 study showed encouraging antitumor activity at generally tolerable doses, which is significant for a disease that has been notoriously difficult to treat.

Revolution Medicines will hold an investor webcast on Friday, October 25, 2024, to discuss the monotherapy data for RMC-6236 and RMC-9805 in PDAC presented at the symposium.

Pancreatic cancer remains a highly fatal disease, often diagnosed at a late stage with limited treatment options. In the U.S., it is estimated that around 60,000 people will be diagnosed, and approximately 50,000 will die from this aggressive cancer in 2024. PDAC, the most common form of pancreatic cancer, accounts for about 92% of cases and is characterized by a high rate of RAS mutations. With a five-year survival rate of roughly 3%, finding effective treatments for metastatic PDAC is crucial.

Revolution Medicines continues to develop RAS(ON) inhibitors, including RMC-9805, aimed at treating various RAS mutation-driven cancers.