Revolution Medicines, Inc. RVMD

Daraxonrasib, a RAS(ON) multi-selective inhibitor, has received Breakthrough Therapy, Orphan Drug, and Commissioner’s National Priority Voucher designations from the FDA for pancreatic cancer. Long-term follow-up data from the Phase I monotherapy cohort in second-line metastatic PDAC showed estimated median progression-free survival (PFS) exceeding 8 months for both G12X and all RAS mutant groups, and estimated median overall survival (OS) of 13.1 months (G12X) and 15.6 months (all RAS mutant), significantly exceeding standard of care. Enrollment for the RASolute 302 Phase III registrational trial in 2L metastatic PDAC is winding down globally, with a data readout expected in 2026.

Encouraging initial results for daraxonrasib in first-line metastatic PDAC were shared. Monotherapy induced tumor regressions in most patients, with an objective response rate (ORR) of 47% and disease control rate (DCR) of 89%. The combination of daraxonrasib plus gemcitabine nab-paclitaxel (GnP) chemotherapy also delivered significant antitumor activity, with an ORR of 55% and DCR of 90%. The RASolute 303 randomized 3-arm Phase III trial in 1L metastatic PDAC, comparing daraxonrasib monotherapy or daraxonrasib plus GnP to GnP alone, is on track to initiate this year.

Revolution Medicines has initiated RASolute 304, a Phase III trial evaluating daraxonrasib monotherapy for 2 years versus observation in approximately 500 patients with resectable PDAC. Patients will be enrolled after surgical resection and at least 4 months of perioperative chemotherapy. The primary endpoint is disease-free survival, aiming to improve outcomes given the high relapse rate of approximately 80% with current standard of care.

The RASolve 301 registrational trial studying daraxonrasib versus docetaxel in previously treated patients with RAS-mutant non-small cell lung cancer (NSCLC) continues to enroll patients across sites in the U.S., Europe, and Japan. The company is also advancing plans to initiate a registrational trial in the first-line metastatic NSCLC setting in 2026, evaluating daraxonrasib in combination with pembrolizumab and chemotherapy, following encouraging initial data on tolerability and early antitumor activity.

Elironrasib, a RAS(ON) G12C inhibitor, demonstrated a confirmed ORR of 42%, DCR of 79%, and a median duration of response (DoR) of 11.2 months in heavily pretreated G12C NSCLC patients who had received a median of 3 prior lines of therapy. Zoldonrasib, a covalent RAS(ON) G12D-selective inhibitor, showed compelling preclinical data in combination with daraxonrasib, leading to maximal RAS G12D inhibition. The first zoldonrasib combination registrational trial in 1L metastatic PDAC is expected in H1 2026, with additional pivotal combination trials for zoldonrasib or elironrasib in 2026.

RMC-5127, an oral tri-complex RAS(ON) G12V-selective inhibitor, is on track to initiate its first-in-human trial in Q1 2026. This asset targets approximately 48,000 patients diagnosed with KRAS G12V mutant cancer annually in the U.S. Revolution Medicines also maintains discovery and clinical collaborations with Tango Therapeutics (for vopimetostat, a PRMT5 inhibitor) and Summit Therapeutics (for ivonescimab, a bispecific PD-1/VEGF inhibitor) to explore diverse combination strategies for RAS-addicted cancers.

Revolution Medicines ended Q3 FY25 with a strong financial position of $1.93 billion in cash and investments, including the receipt of a $250 million royalty monetization tranche from Royalty Pharma, with an additional $1.75 billion in future committed capital. The company is scaling its organization to support global development and commercialization ambitions, making key appointments such as Dr. Alan Sandler as Chief Development Officer, Alicia Gardner as SVP & GM U.S. region, and Gerwin Winter as SVP & GM European region.