On October 5, 2026 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, reported that it has begun treating patients in RASolute 309, a global, randomized Phase 3 clinical trial evaluating the combination of RASONQUE (daraxonrasib), a RAS(ON) multi-selective inhibitor, and zoldonrasib, an investigational RAS(ON) G12D-selective inhibitor, as a first-line treatment in adult patients with metastatic RAS G12D pancreatic adenocarcinoma (PDAC).

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"RAS G12D is the most common RAS variant in PDAC," said Alan Sandler, M.D., chief development officer of Revolution Medicines. "In preclinical studies, the combination of RAS(ON) multi-selective and G12D-selective inhibitors achieved deeper and more sustained suppression of RAS signaling than either agent alone, accompanied by greater tumor control. Likewise, initial clinical data showed that RASONQUE plus zoldonrasib delivered compelling antitumor activity in patients with previously treated metastatic PDAC, with a manageable safety and tolerability profile. In the context of the unmet need in this patient population, these findings informed the design of the first-line RASolute 309 trial in patients with PDAC. RASolute 309 is the first Phase 3 study evaluating a RAS(ON) inhibitor doublet approach and it marks an important milestone in our efforts to advance a range of potential treatment options for patients with RAS-driven cancers across tumor types and treatment settings."

RASolute 309 (NCT07805954) is a global, randomized, open-label Phase 3 trial evaluating RASONQUE plus zoldonrasib compared with gemcitabine and nab-paclitaxel (GnP) as a first-line treatment in adult patients with metastatic RAS G12D PDAC. The dual primary endpoints are progression-free survival (PFS) and overall survival. Key secondary endpoints include PFS, objective response rate, duration of response, safety and tolerability, pharmacokinetics, and patient-reported outcomes.

About Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma, or PDAC, is the most common form of pancreatic cancer and among the most challenging malignancies. Approximately 55,000 people are diagnosed with PDAC in the U.S. each year, and more than 50,000 die from the disease.1,2 Because early-stage pancreatic cancer often causes few or no symptoms, approximately 80% of patients are diagnosed after the disease has spread, when treatment options are more limited. For patients with metastatic PDAC, the five-year relative survival rate is approximately 3% in the U.S.3,4 RAS G12D is the most prevalent RAS mutation subtype in PDAC, occurring in 40% of patients.5

About Zoldonrasib

Zoldonrasib is an investigational, oral, RAS(ON) G12D-selective, covalent tri-complex inhibitor that binds to cyclophilin A, creating a binary complex that binds to and inhibits the active, oncogenic RAS(ON) G12D mutation. RAS G12D is the most prevalent RAS mutation, accounting for 29% of all RAS-driven cancers.5 Across tumor types, approximately 61,000 new patients with RAS G12D cancers are estimated each year in the U.S., and no targeted therapy is currently approved for these patients.6 Zoldonrasib is currently being evaluated as a monotherapy and in combination with other therapies, including with RASONQUE, Revolution Medicines’ RAS(ON) multi-selective inhibitor, as well as standard of care regimens in lung and gastrointestinal cancers.

About RASONQUE (daraxonrasib)

RASONQUE (daraxonrasib) is an oral, RAS(ON) multi-selective, noncovalent, tri-complex inhibitor, approved by the U.S. FDA for the treatment of adult patients with metastatic pancreatic adenocarcinoma (PDAC) who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.7 RASONQUE is being investigated through a global Phase 3 registrational program in patients with PDAC and metastatic RAS mutant non-small cell lung cancer. Outside the U.S., RASONQUE is an investigational agent that has not been approved by any regulatory authority.

U.S. FDA APPROVED INDICATION

RASONQUE is indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.

IMPORTANT SAFETY INFORMATION FOR U.S. APPROVED INDICATION

RASONQUE is associated with the following Warnings and Precautions: Dermatologic and Soft Tissue Toxicity, Stomatitis and Oral Disorders, Diarrhea, Gastrointestinal Perforation, Interstitial Lung Disease (ILD)/Pneumonitis, and Embryo-Fetal Toxicity.

Serious adverse reactions occurred in 30% of patients treated with RASONQUE. Serious adverse reactions occurring in ≥ 2% of patients treated with RASONQUE were diarrhea (3.7%), pyrexia (3.3%), sepsis (2.9%), fatigue (2.1%), and hemorrhage (2.1%).

The most common (≥ 20%) adverse reactions in patients treated with RASONQUE were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.

(Press release, Revolution Medicines, OCT 5, 2026, View Source [SID1234673187])