Revolution Medicines (RVMD) Status Update summary

Key clinical development updates

• RMC-6236 advanced to phase III for second-line PDAC and is planned for phase III in NSCLC in early 2025, with strong efficacy and tolerability in both indications.

• In PDAC, RMC-6236 at 300 mg daily achieved a 36% objective response rate and median progression-free survival of 8.8 months; six-month overall survival was 100% (KRAS G12X) and 97% (RAS mutant).

• In NSCLC, RMC-6236 at 120–220 mg daily showed a 38% objective response rate, median progression-free survival of 9.8 months, and median overall survival of 17.7 months.

• Combination of RMC-6236 with pembrolizumab in NSCLC demonstrated favorable safety and combinability, with no significant liver toxicity and high dose intensity.

• RMC-6291 + RMC-6236 doublet in refractory colorectal cancer achieved a 25% objective response rate and 92% disease control rate, with manageable safety.

Dose optimization and safety insights

• RMC-6236 dose set at 300 mg daily for PDAC and 200 mg daily for NSCLC, based on tolerability and dose intensity data.

• Safety profiles for RMC-6236 and combinations were generally manageable, with most adverse events being low grade and dose reductions mainly related to RMC-6236.

• No Grade 3 or higher treatment-related adverse events in more than 10% of patients at optimal doses; mean dose intensity was high across studies.

• QTc prolongation observed only with RMC-6291, managed by dose adjustment; no additive safety concerns in combinations.

• Most common TRAEs included rash, diarrhea, and nausea, with low rates of discontinuation.

Strategic priorities and future directions

• Plans to expand RMC-6236 into first-line PDAC and NSCLC, including chemo-free regimens with RAS(ON) inhibitor doublets and pembrolizumab.

• Ongoing and planned phase III trials for RMC-6236 in PDAC and NSCLC, and further studies to optimize dosing and assess efficacy across broader RAS mutation subtypes.

• Continued development of RAS(ON) inhibitor doublets and triplets, including with pembrolizumab, in various tumor types.

• Open to external collaborations for combination studies, including with Tango Therapeutics for PRMT5 inhibitor combinations.

• Emphasis on dose optimization to maximize patient benefit and maintain high dose intensity for prolonged treatment efficacy.