Daraxonrasib PDAC Data Published in NEJM as FDA Allows Expanded Access

In a week that saw the FDA allow expanded access to daraxonrasib for the treatment of pancreatic ductal adenocarcinoma (PDAC), important foundational data for the RAS inhibitor were published in The New England Journal of Medicine.^1,2

The data published in NEJM are from the PDAC cohort of the open-label, multicenter phase 1/2 RMC-6236-001 trial (NCT05379985). These early-phase results led to the launch of the phase 3 RASolute 302 trial (NCT06625320), which supported the FDA’s decision to allow expanded access to daraxonrasib prior to the drug’s approval.³

“RAS mutations are a central driver of disease across multiple solid tumors, including particularly pancreatic ductal adenocarcinoma. There is significant room for improvement in outcomes over current standard of care—cytotoxic chemotherapies that are not targeted to these underlying RAS cancer drivers,” Alan Sandler, MD, chief development officer of Revolution Medicines, stated in a news release.

“Data from the Phase 1/2 trial show that daraxonrasib demonstrated promising clinical antitumor activity and durable responses, with an acceptable safety and tolerability profile, in patients with previously treated metastatic RAS mutant PDAC. These results, along with those from our Phase 3 trial, RASolute 302, strengthen our confidence in daraxonrasib’s potential to establish an important new treatment option for patients with pancreatic cancer and other RAS-addicted cancers,” added Sandler.

Phase 1/2 Daraxonrasib Data

Efficacy data from the phase 1/2 trial showed that in 26 patients with RAS G12 mutations who received daraxonrasib at 300 mg in the second-line setting, the objective response rate was 35%. The median duration of response in this cohort was 8.2 months with a median progression-free survival (PFS) of 8.5 months and a median overall survival (OS) of 13.1 months.

In the broader group of 38 patients with RAS G12, G13, or Q61 mutations, 29% of patients achieved an objective response. The median duration of response in this group was 8.2 months, median PFS was 8.1 months, and median OS reached 15.6 months.

Among the 168 PDAC patients who received daraxonrasib at doses up to 300 mg, treatment-related adverse events of any grade were reported in 96% of patients. Grade 3 or higher treatment-related events occurred in approximately one-third of patients, at a rate of 30%. The adverse events occurring in at least 10% of patients included rash, diarrhea, nausea, stomatitis or mucositis, vomiting, and fatigue. This safety profile is generally consistent with other RAS-targeted agents and considered manageable in the context of the disease's severity and the historical lack of effective options in this setting.

Overall, the phase 1/2 study enrolled patients with advanced solid tumors harboring activating RAS mutations. Dose escalation ranged from 10 mg to 400 mg orally once daily, with 300 mg selected as the phase 3 dose based on the totality of pharmacokinetic and efficacy data. The NEJM report focuses specifically on the 168 study patients with previously treated RAS-mutated PDAC who received daraxonrasib at a dose of 300 mg or less.

RASolute 302 Trial of Daraxonrasib

Survival results in the RASolute 302 trial showed that the median OS in the intent-to-treat population 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 PFS and OS in patients with tumors harboring RAS G12 mutations.⁴

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

Overall, 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.⁵

The primary end points 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.⁵

The FDA previously 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.

The full primary and final analysis from RASolute 302 are being presented by Brian Wolpin, MD, MPH in the plenary session at the 2026 ASCO Annual Meeting.

REFERENCES

1. Wolpin BM, Park W, Garrido-Laguna I, et al; RMC-6236-001 Investigators. Daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer. N Engl J Med. 2026;394(18). doi:10.1056/NEJMoa2505783

2. Revolution Medicines, Inc. Revolution Medicines announces publication in New England Journal of Medicine of phase 1/2 clinical data on daraxonrasib in pancreatic cancer. Globe Newswire. Published and accessed May 6, 2026. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-publication-new-england-journal

3. U.S. Food and Drug Administration. FDA permits expanded access for investigational pancreatic cancer drug. FDA News Release. Published April 30, 2026. Accessed May 7, 2026. https://tinyurl.com/58rz3ue7

4. Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines. April 13, 2026. Accessed May 7, 2026. https://tinyurl.com/y6z9rxmy

5. 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 May 7, 2026. https://clinicaltrials.gov/study/NCT06625320