On June 23, 2026 Revolution Medicines, a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported that it has begun treating patients in RASolute 305, a global, randomized Phase 3 clinical trial evaluating zoldonrasib in combination with standard of care chemotherapy as a first line treatment in patients with metastatic RAS G12D pancreatic ductal adenocarcinoma (PDAC).
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"Pancreatic cancer is a RAS-driven disease, and we recently reported that daraxonrasib, our RAS(ON) multi-selective inhibitor, significantly improved overall survival, progression-free survival, response rates, and preservation of measures of quality of life versus standard of care chemotherapy in second line treatment of patients with metastatic pancreatic cancer across a range of RAS genotypes. These unprecedented findings provide important clinical validation of RAS(ON) inhibition in pancreatic cancer and support its evaluation earlier in the treatment course," said Alan Sandler, M.D., chief development officer of Revolution Medicines.
"RAS G12D, the most common RAS subtype in pancreatic cancer, is associated with particularly poor clinical outcomes. Early studies of zoldonrasib, our oral RAS(ON) G12D-selective covalent inhibitor, have demonstrated encouraging clinical activity and safety. The RASolute 305 trial is evaluating whether combining zoldonrasib with chemotherapy can improve outcomes in first line treatment for metastatic RAS G12D pancreatic cancer. Both RASolute 305 and RASolute 303, a separate ongoing Phase 3 trial evaluating daraxonrasib in first line pancreatic cancer, reflect our broad commitment to studying RAS(ON) inhibitors with differentiated profiles across a range of unmet medical needs in pancreatic cancer," added Dr. Sandler.
RASolute 305 (NCT07621718) is a global, randomized, double-blind placebo-controlled clinical trial evaluating zoldonrasib plus investigator’s choice of standard of care chemotherapy compared with placebo plus investigator’s choice of chemotherapy in patients with previously untreated metastatic RAS G12D PDAC. Investigator’s choice of chemotherapy includes modified FOLFIRINOX or gemcitabine plus nab-paclitaxel. The primary endpoints are progression-free survival and overall survival. Key secondary endpoints include additional measures of antitumor activity, safety and tolerability, and patient reported outcomes.
About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that approximately 60,000 people are diagnosed annually with pancreatic cancer, and about 50,000 people will die from this aggressive disease.1
Pancreatic ductal adenocarcinoma, or PDAC, is the most common form of pancreatic cancer. Due to the lack of early symptoms and effective detection methods, approximately 80% of patients are diagnosed with advanced or metastatic disease. PDAC is the most commonly RAS-driven malignancy of all major cancers, with more than 90% of patients have tumors that harbor RAS mutations.2 RAS G12D is the most prevalent RAS mutation subtype in PDAC, occurring in 40% of patients, and has been associated with poorer outcomes than RAS wild-type disease and certain other RAS-mutant subgroups.2-5 Metastatic PDAC remains a leading cause of cancer-related death in the U.S., with a five-year survival rate of approximately 3%. 6,7
About Zoldonrasib
Zoldonrasib is a tri-complex inhibitor that binds to cyclophilin A, creating a complex that selectively recognizes and inhibits the active, oncogenic RAS(ON) G12D mutation. RAS G12D is the most prevalent RAS mutation, accounting for 29% of all RAS cancers.2 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.8 Zoldonrasib is currently being evaluated as a monotherapy and in combination with other therapies, including with Revolution Medicines’ RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236), as well as standard of care regimens in lung and gastrointestinal cancers.
(Press release, Revolution Medicines, JUN 23, 2026, View Source [SID1234668926])