Daraxonrasib Shows Significant OS Benefit in Metastatic Pancreatic Cancer

Daraxonrasib (RMC-6236), an investigational oral RAS(ON) multi-selective inhibitor, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with standard chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma, according to topline results from the phase 3 RASolute 302 trial (NCT06625320).¹

In the intent-to-treat population, the median OS was 13.2 months with daraxonrasib vs 6.7 months for chemotherapy, translating to a 60% reduction in the risk of death (HR, 0.40; P <.0001). The trial also met its primary end points of progression-free survival (PFS) and OS in patients with tumors harboring RAS G12 mutations.

Regarding safety, daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals.

“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life,” Brian M. Wolpin, MD, MPH, professor of medicine at Harvard Medical School, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and principal investigator for the RASolute 302 trial, stated in a news release.¹ 

“The widely anticipated results of this study indicate that daraxonrasib provides a clear and highly meaningful step forward for patients with pancreatic cancer who have experienced progression on prior treatment, typically chemotherapy. I believe that this new approach is a very important advance for the field that I expect will be practice-changing for physicians and improve the care for patients with previously treated metastatic pancreatic cancer, added Wolpin.

Trial Design and Enrollment

RASolute 302 is an ongoing, global, randomized, controlled registrational trial enrolling patients with previously treated metastatic PDAC. Patients were randomized to daraxonrasib 300 mg orally once daily or investigator's choice of standard-of-care cytotoxic chemotherapy. Enrollment included patients across a broad range of RAS variants: including G12D, G12V, and G12R mutations, as well as patients with RAS wild-type tumors.

Primary endpoints were PFS and OS in patients with RAS G12 mutation–positive tumors, as assessed by Blinded Independent Central Review. Secondary end points included PFS and OS in the full intent-to-treat population, objective response rate, duration of response, and patient-reported quality of life.²

Molecular Rationale

Daraxonrasib is designed as a non-covalent, multi-selective inhibitor of RAS(ON) proteins, targeting the active, GTP-bound state of both wild-type and mutant RAS isoforms and suppressing downstream effector signaling. Unlike earlier RAS-targeted agents that were limited to specific alleles such as KRAS G12C, daraxonrasib is designed to address a broader spectrum of RAS variants, which is particularly relevant in PDAC given the diversity of RAS mutations observed in this cancer type.

The FDA has granted daraxonrasib breakthrough therapy designation and orphan drug designation for previously treated metastatic PDAC harboring G12 mutations. Daraxonrasib has also been selected for the FDA Commissioner's National Priority Voucher pilot program. Revolution Medicines intends to submit a New Drug Application to the FDA under this pathway and to submit data to other global regulatory authorities.

“In this pivotal trial, daraxonrasib as a targeted medicine delivered a dramatic improvement in overall survival in patients with previously treated metastatic pancreatic cancer compared to standard of care chemotherapy, consistent with earlier findings. These results represent a potentially transformative advance for patients and underscore daraxonrasib’s potential to redefine the treatment landscape. We are moving with urgency toward global regulatory submissions and remain committed to rapidly advancing this therapy for patients with a broad range of RAS-addicted cancers. We are deeply grateful to the patients, families, investigators, and study teams whose participation made the RASolute 302 trial possible, and we look forward to sharing detailed results with the scientific and clinical communities,” Mark A. Goldsmith, MD, PhD, chief executive officer and chairman of Revolution Medicines, stated in the news release.¹

“We believe these results firmly validate our pioneering approach to targeting common RAS-addicted cancers through RAS(ON) inhibition, exemplified today by four clinical-stage, investigational drugs with differentiated profiles. This class of inhibitors reflects more than 15 years of investment in groundbreaking scientific research, including creative work from Warp Drive Bio, acquired by Revolution Medicines in 2018, which established the initial technology foundation we have developed into a robust innovation engine for delivering and sustaining our compelling pipeline,” added Goldsmith.

REFERENCES

1. Revolution Medicines. Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. Press release. April 13, 2026. Accessed April 14, 2026. Revolution Medicines. https://tinyurl.com/2sj6rdst

2. Phase 3 study of daraxonrasib (RMC-6236) in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) (RASolute 302). ClinicalTrials.gov. Updated December 12, 2025. Accessed April 13, 2026. https://clinicaltrials.gov/study/NCT06625320