Revolution Medicines Begins Treating Patients in Phase 3 RASolute 309 Trial Evaluating RASONQUE™ (daraxonrasib) Plus Zoldonrasib as First-Line Treatment for Metastatic RAS G12D Pancreatic Cancer
REDWOOD CITY, Calif., Oct. 05, 2026 (GLOBE NEWSWIRE) -- 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 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).
“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.
Please see U.S. Full Prescribing Information for RASONQUE
About Revolution Medicines, Inc.
Revolution Medicines is a global, commercial-stage oncology company dedicated to discovering, developing and delivering innovative medicines for patients with RAS-addicted cancers. Leveraging its differentiated RAS(ON) tri-complex inhibitor platform, the company is advancing a broad, integrated portfolio of oral RAS(ON) inhibitors designed to directly target the active, cancer-driving state of RAS. Founded on rigorous scientific inquiry and a willingness to challenge long-held assumptions, Revolution Medicines is committed to changing the trajectory of disease for patients with RAS-addicted cancers worldwide. For more information, visit www.revmed.com and follow Revolution Medicines on LinkedIn, X (Twitter) and Instagram.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding the broad potential of RAS(ON) inhibition; prevalence of certain cancer types and mutations; treatment practices; the company’s development strategy; possible adverse reactions; and progression of clinical studies and findings from these studies, including the tolerability, safety, and potential efficacy of the company's candidates being studied.
Forward-looking statements are typically, but not always, identified by the use of words such as "aims," "anticipate," "believe," "estimate," "expect," "plan," "potential," "project," "up to," "will" and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company's development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company's programs' development stages, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company's ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company's capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company's business of global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the "SEC") on August 5, 2026, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances, or to reflect the occurrence of unanticipated events.
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References
1 Oracle CancerMPact Patient Metrics, Stage IV newly incident + recurrent from earlier stages. Accessed July 2026.
2 Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
3 Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: Advances and challenges. Cell. 2023;186(8):1729-1754. doi:10.1016/j.cell.2023.02.014
4 American Cancer Society. Survival Rates for Pancreatic Cancer. Available at: https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html. Accessed September 2026.
5 Lee JK, Sivakumar S, Schrock AB, et al. Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol. 2022;6(1);91. doi:10.1038/s41698-022-00334-z
6 Estimated using tumor mutation frequencies from Foundation Medicine Insights March 2022 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2023.
7 RASONQUE (daraxonrasib) Prescribing Information. Redwood City, CA: Revolution Medicines, Inc.; August 2026.