Revolution Medicines, Inc. (NASDAQ:RVMD), a global, commercial-stage oncology company dedicated to discovering, developing and delivering innovative medicines for patients with RAS-addicted cancers, today announced that The New England Journal of Medicine (NEJM) has published a report describing data from the Phase 1/2 clinical trial evaluating RASONQUE (daraxonrasib), an oral, RAS(ON) multi-selective inhibitor, in patients with previously treated advanced RAS mutant non-small cell lung cancer (NSCLC).

"RAS mutations are among the most common oncogenic drivers in lung cancer, occurring in approximately 30 percent of cases. Targeted RAS inhibition has demonstrated clinical benefit in patients with RAS G12C non-small cell lung cancer following initial treatment with chemotherapy and immunotherapy, but there are no targeted therapies for patients with other RAS tumor mutations. The rates of objective response, disease control and survival observed in patients treated with RASONQUE in this Phase 1/2 study support the ongoing global, randomized pivotal RASolve 301 trial evaluating RASONQUE in previously treated RAS mutant non-small lung cancer. Together with the recent FDA approval of RASONQUE in metastatic pancreatic cancer, the data reported in the NEJM publication provide additional clinical validation of our broad RAS(ON) multi-selective and mutant-selective approach across major RAS-driven cancers," said Alan Sandler, M.D., chief development officer of Revolution Medicines.

The results published in NEJM are based on the Phase 1/2 RMC-6236-001 trial (NCT05379985), with a July 21, 2025 data cut off. The trial evaluated the safety and efficacy of once-daily doses of RASONQUE 300 mg or less in 136 patients with second-line or later NSCLC with tumors carrying diverse RAS mutations other than RAS G12C, and whose disease had progressed following, or who were intolerant to, platinum-based chemotherapy and anti-PD-(L)1 therapy.

RASONQUE demonstrated dose-dependent antitumor activity and exhibited a manageable safety profile in the Phase 1/2 trial. Within the 160 mg to 220 mg dose group, a subgroup of 38 docetaxel-naïve patients had previously received first- or second-line platinum-based chemotherapy and anti-PD-(L)1 therapy. In this subgroup, the confirmed objective response rate was 42% (95% confidence interval [CI], 26%-59%) and a disease control rate of 89% (95% CI, 75%-97%). The median progression-free survival was 8.3 months (95% CI: 4.0-12.5) and median overall survival was 16.0 months (95% CI, 9.5-not estimable). At these dose levels, Grade 3 treatment-related adverse events (TRAEs) occurred in 25% of patients, most commonly rash (8%) and diarrhea (3%). No Grade 4 or Grade 5 TRAEs were reported within this dose range.

The results from this Phase 1/2 trial informed the design and initiation of RASolve 301 (NCT06881784), the company’s ongoing global, randomized, open-label Phase 3 trial evaluating RASONQUE compared with docetaxel in patients with previously treated, locally advanced or metastatic RAS mutant NSCLC. RASONQUE is an investigational agent for the treatment of RAS mutant NSCLC.