Revolution Medicines Begins Treating Patients in RASolute 305, a Phase 3 Clinical Trial Evaluating Zoldonrasib in Combination with Chemotherapy as a First Line Treatment for Patients with RAS G12D Metastatic Pancreatic Cancer
Rhea-AI Summary
Revolution Medicines (RVMD) has begun treating patients in RASolute 305, a global randomized Phase 3 trial of zoldonrasib plus standard chemotherapy as first line treatment for metastatic RAS G12D pancreatic ductal adenocarcinoma (PDAC).
The double-blind, placebo-controlled study compares zoldonrasib plus investigator’s choice of modified FOLFIRINOX or gemcitabine plus nab-paclitaxel versus placebo plus chemotherapy. Primary endpoints are progression-free survival and overall survival, with key secondary endpoints including antitumor activity, safety, tolerability, and patient-reported outcomes.
Positive
- Initiation of global randomized Phase 3 RASolute 305 trial in first line metastatic RAS G12D PDAC
- Evaluation of zoldonrasib combined with standard chemotherapy regimens (modified FOLFIRINOX or gemcitabine plus nab-paclitaxel)
- Trial designed with hard clinical endpoints: progression-free survival and overall survival as co-primary endpoints
- Complementary Phase 3 program including separate RASolute 303 trial of daraxonrasib in first line pancreatic cancer
- Earlier daraxonrasib data reportedly improved survival, response rates, and quality-of-life measures versus standard chemotherapy in second line metastatic pancreatic cancer
Negative
- None.
News Market Reaction – RVMD
In the Jun 23 session, RVMD gained 2.23%, reflecting a moderate positive market reaction.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Previous Clinical trial Reports
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| May 31 | Phase 3 results | Positive | +3.9% | Pivotal Phase 3 RASolute 302 data showing large survival benefit in PDAC. |
| May 06 | NEJM publication | Positive | -5.7% | NEJM Phase 1/2 daraxonrasib data plus confirmation of positive RASolute 302 topline. |
| Apr 21 | AACR data update | Positive | -4.4% | Updated Phase 1/2 first-line daraxonrasib data with high response rates and PFS. |
| Apr 21 | ASCO preview | Positive | +1.8% | Announcement of detailed Phase 3 RASolute 302 results at ASCO plenary session. |
| Apr 13 | Topline Phase 3 | Positive | +41.4% | Topline RASolute 302 data with unprecedented overall survival benefit in metastatic PDAC. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Clinical trial headlines for RVMD have produced mixed but often strong reactions, with slightly more aligned than divergent moves.
Key Terms
progression-free survival medical
overall survival medical
patient reported outcomes medical
placebo-controlled medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
REDWOOD CITY, Calif., June 23, 2026 (GLOBE NEWSWIRE) -- Revolution Medicines, a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced 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).
“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
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
About Revolution Medicines, Inc.
Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor; and RMC-5127, a RAS(ON) G12V-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn.
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, including in pancreatic cancer; the ability of daraxonrasib or zoldonrasib to improve patient outcomes; 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 the 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’ Annual Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 6, 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.
Revolution Medicines Media & Investor Contact:
media@revmed.com
investors@revmed.com
References
1 Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
2 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
3 Yousef, A., Yousef, M., Chowdhury, S. et al. Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma. NPJ Precis Oncol. 2024;8:27. https://doi.org/10.1038/s41698-024-00505-0
4 Qian ZR, Rubinson DA, Nowak JA, et al. Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2018;4(3):e173420. doi:10.1001/jamaoncol.2017.3420
5 Norton C, Shaw MS, Rubnitz Z, et al. KRAS Mutation Status and Treatment Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma. JAMA Netw Open. 2025;8(1):e2453588. doi:10.1001/jamanetworkopen.2024.53588
6 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
7 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 June 2026.
8 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.
