FDA Permits Expanded Daraxonrasib Access in Previously Treated Metastatic PDAC

The FDA has issued a “safe to proceed” letter for daraxonrasib, authorizing the initiation of an expanded access program (EAP) for the treatment of patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC), according to press releases from the FDA and the developer, Revolution Medicines.^1,2

This regulatory action allows the company to provide the investigational RAS(ON) multi-selective inhibitor to eligible patients in a controlled and monitored setting, consistent with FDA regulations governing investigational medicines. Requests for expanded access of the drug must be submitted to the developer by physicians licensed in the US on behalf of eligible patients.

Reportedly, the FDA approved the expanded access request on April 28th and signed it on April 30th. FDA Commissioner Marty Makary, MD, MPH, stated, “Granting the request 2 days after receiving the expanded access application reflects the FDA's strong commitment to facilitate early access to therapies for serious and life-threatening conditions, including pancreatic cancer.”

The authorization follows the drug’s receipt of breakthrough therapy and orphan drug designation, as well as a national priority voucher from the agency.

What data support the use of daraxonrasib in metastatic pancreatic cancer?

The EAP authorization is underpinned by “unprecedented” efficacy results from the pivotal phase 3 RASolute 302 trial (NCT06625320), which evaluated daraxonrasib in patients with metastatic PDAC who had received prior conventional treatment.³ Data from the trial demonstrated that daraxonrasib nearly doubled the average survival time for this patient population, with a median overall survival (OS) of 13.2 months, compared with 6.7 months for those receiving standard-of-care chemotherapy (HR, 0.40; P <.0001).

It was also reported that daraxonrasib treatment was generally well tolerated, with a manageable safety profile and no new safety signals.

Full results from the RASolute 302 trial are currently slated for presentation at the 2026 American Society of Clinical Oncology Annual Meeting. They will be shared in the plenary session.

In an interview with CancerNetwork, Diane Simeone, MD, director of the Moores Cancer Center at University of California San Diego Health, said, “This is a substantial benefit for patients with metastatic pancreas cancer, who represent about half of the patients we see. These findings are impactful for improving both the length and quality of life for patients."

What are the trial design and eligibility criteria for the daraxonrasib treatment protocol?

Daraxonrasib is an oral pill designed as a RAS(ON) inhibitor that suppresses oncogenic variants of RAS proteins to inhibit tumor formation and growth. Eligible patients were at least 18 years or older with histologically or cytologically confirmed PDAC with metastatic disease. They were also required to have an ECOG performance status of 0 or 1, adequate organ function, and measurable disease per RECIST v1.1 guidelines.⁴ Those with documented RAS mutations at codon 12, 13, or 61 were enrolled.

All patients enrolled were randomly assigned in a 1:1 ratio to receive oral daraxonrasib at 300 mg once daily or investigator’s choice of standard cytotoxic chemotherapy.

The primary end points of the study were progression-free survival per blinded independent central review and OS in those harboring RAS G12 mutations. Among the secondary end points were objective response rate, duration of response, and quality of life.

In a separate CancerNetwork-exclusive interview, Asfar Azmi, PhD, a professor of oncology at Wayne State University School of Medicine and the director of pancreas cancer research at the Karmanos Cancer Institute in Detroit, Michigan, said regarding the daraxonrasib efficacy findings, “To see such activity in pancreatic cancer is remarkable. We have not seen such a thing in the last…20 years in the pancreatic cancer space. This is definitely very exciting news.”

References

1. FDA permits expanded access for investigational pancreatic cancer drug. News release. FDA. Published April 30, 2026. Accessed May 1, 2026. https://tinyurl.com/4xbhx3pd
2. Revolution Medicines statement on FDA expanded access authorization for daraxonrasib in patients with previously treated metastatic pancreatic cancer. News release. Revolution Medicines. May 1, 2026. Accessed May 1, 2026. https://tinyurl.com/5ftk9vcj
3. Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines Inc. April 13, 2026. Accessed May 1, 2026. https://tinyurl.com/44t5vh5d
4. Phase 3 study of daraxonrasib (RMC-6236) in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) (RASolute 302). ClinicalTrials.gov. Updated April 27, 2026. Accessed May 1, 2026. https://tinyurl.com/5n8ns7xz