Revolution Medicines Announces FDA Breakthrough Therapy Designation for Daraxonrasib in Previously Treated Metastatic Pancreatic Cancer with KRAS G12 Mutations

Rhea-AI Summary

Revolution Medicines (NASDAQ: RVMD) has received FDA Breakthrough Therapy Designation for daraxonrasib, targeting previously treated metastatic pancreatic cancer with KRAS G12 mutations. The designation is based on promising Phase 1 trial data and aims to expedite development and review of this potential treatment. The company is currently conducting RASolute 302, a Phase 3 registrational study expected to complete enrollment in 2025, with results anticipated in 2026. The study focuses on patients with pancreatic ductal adenocarcinoma (PDAC), where over 90% of cases carry RAS mutations, with approximately 85% specifically having KRAS G12 mutations. The trial's dual primary endpoints include progression-free survival and overall survival in the core patient population.

Positive

• FDA Breakthrough Therapy Designation received, potentially expediting drug development and review process
• Phase 1 clinical trial showed encouraging results for daraxonrasib in treating pancreatic cancer
• Large addressable market with over 90% of PDAC patients having RAS mutations
• Phase 3 trial enrollment expected to complete this year, with results in 2026

Negative

• Final Phase 3 trial results not expected until 2026
• Drug still requires successful Phase 3 results and full FDA approval
• Limited to specific mutation types, primarily KRAS G12 mutations

Insights

Oncology Expert

FDA Breakthrough Therapy Designation for daraxonrasib significantly accelerates Revolution Medicines' path toward potentially transformative pancreatic cancer treatment.

The FDA's Breakthrough Therapy Designation for daraxonrasib represents a significant regulatory milestone that could accelerate the development pathway for Revolution Medicines' RAS(ON) multi-selective inhibitor. This designation is particularly meaningful given the devastating nature of pancreatic ductal adenocarcinoma (PDAC) and the limited treatment options currently available.

The designation hinges on promising early clinical evidence from the Phase 1 RMC-6236-001 trial in previously treated metastatic PDAC patients. What makes daraxonrasib particularly compelling is its target population - patients with KRAS G12 mutations, which account for approximately 85% of PDAC cases. The high prevalence of these mutations creates a substantial addressable patient population.

The ongoing Phase 3 RASolute 302 study represents the critical next step, with dual primary endpoints of progression-free survival and overall survival in the core population. The trial design is noteworthy for its inclusion of both a focused core population (KRAS G12X mutations) and an expanded population including additional mutation types. This stratified approach optimizes the potential for demonstrating efficacy in well-defined genetic subgroups.

The expected completion of enrollment this year positions the company for a potential data readout in 2026. The Breakthrough Designation provides several regulatory advantages, including intensive FDA guidance, organizational commitment from senior managers, and eligibility for accelerated approval and priority review. These benefits could substantially compress the timeline from positive data to potential market approval.

• Breakthrough Therapy Designation based on promising early clinical evidence observed with daraxonrasib in patients with pancreatic ductal adenocarcinoma (PDAC)
  
  
• RASolute 302, a Phase 3 registrational study of daraxonrasib in patients with previously treated metastatic PDAC, expected to substantially complete enrollment this year
  

REDWOOD CITY, Calif., June 23, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to daraxonrasib, the company’s RAS(ON) multi-selective inhibitor, for previously treated metastatic PDAC in patients with KRAS G12 mutations.

The Breakthrough Therapy Designation is based on encouraging data from the Phase 1 RMC-6236-001 clinical trial evaluating daraxonrasib in patients with previously treated metastatic PDAC.

“This Breakthrough Therapy Designation underscores the enormous need for new treatments for patients with pancreatic cancer and highlights the potentially important role the investigational drug, daraxonrasib, may have in helping patients living with this disease,” said Mark A. Goldsmith M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “We look forward to substantially completing enrollment of the RASolute 302 study this year to enable an expected readout in 2026, and should the results support it, working closely with the FDA and other regulatory agencies around the world to bring daraxonrasib to patients as quickly as possible.”

Breakthrough Therapy Designation is intended to expedite the development and review of potential new medicines designed to treat serious conditions and address significant unmet medical needs. The medicine needs to have shown encouraging preliminary clinical evidence that demonstrates substantial improvement on a clinically significant endpoint over available medicines.

More than 90% of patients living with PDAC have tumors carrying a RAS cancer driver mutation with ~85% carrying a KRAS G12 mutation. Revolution Medicines is currently enrolling patients in RASolute 302, a global Phase 3 registrational study of daraxonrasib in patients with previously treated metastatic PDAC. The study design focuses on a core population of patients with PDAC harboring RAS mutations at position 12 (RAS G12X) and an expanded population that includes patients with tumors harboring RAS mutations at position G12 (RAS G12X), G13 (RAS G13X) or Q61 (RAS Q61X), or those without any identified targetable mutation. The dual primary endpoints for the study are progression-free survival (PFS) and overall survival (OS) in the core patient population. Key secondary endpoints include PFS and OS in the expanded population of patients. Additional information about RASolute 302 (NCT06625320) is available at clinicaltrials.gov.

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 in 2024, approximately 60,000 people will be diagnosed with pancreatic cancer¹, and about 50,000 people will die from this aggressive disease.

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) and its variants, accounts for approximately 92% of all pancreatic cancer cases². Due to the lack of early symptoms and detection methods, approximately 80% of patients are diagnosed with PDAC at an advanced or metastatic stage. It is the most commonly RAS-addicted of all major cancers, and more than 90% of patients have tumors that harbor RAS mutations³. Metastatic PDAC remains one of the most common causes of cancer-related deaths in the U.S., with a five-year survival rate of approximately 3%⁴.

About Daraxonrasib
Daraxonrasib (RMC-6236) is an oral, direct RAS(ON) multi-selective inhibitor with the potential to help address a wide range of cancers driven by oncogenic RAS mutations. Daraxonrasib suppresses RAS signaling by blocking the interaction of RAS(ON) with its downstream effectors. It does so by targeting oncogenic RAS mutations G12X, G13X and Q61X that are common drivers of major cancers, including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).

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; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter 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 progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company’s candidates being studied and the durability of these results; dosing and enrollment in the company’s clinical trials; potential regulatory interactions by the company; and the ability of the company to bring its clinical candidates to patients. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," 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’ current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, 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’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 7, 2025, 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

¹ Siegel RL, et al. CA Cancer J Clin. 2024;74:12-49.
² Hallbrook CJ, et al. Cell. 2023;186:1729-1754.
³ 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.
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 June 2025.

FAQ

What is the significance of RVMD's FDA Breakthrough Therapy Designation for daraxonrasib?

The designation expedites development and review of daraxonrasib for treating metastatic pancreatic cancer with KRAS G12 mutations, based on promising Phase 1 results.

What percentage of pancreatic cancer patients could potentially benefit from Revolution Medicines' daraxonrasib?

Over 90% of pancreatic ductal adenocarcinoma patients have RAS mutations, with approximately 85% specifically carrying KRAS G12 mutations that the drug targets.

When will Revolution Medicines complete the Phase 3 trial for daraxonrasib?

The Phase 3 RASolute 302 trial is expected to complete enrollment in 2025, with results anticipated in 2026.

What are the primary endpoints of RVMD's RASolute 302 Phase 3 trial?

The trial has dual primary endpoints: progression-free survival (PFS) and overall survival (OS) in the core patient population.

Which specific mutations does Revolution Medicines' daraxonrasib target?

Daraxonrasib targets RAS mutations at positions G12, G13, and Q61, with a primary focus on KRAS G12 mutations.