The FDA has approved daraxonrasib (Rasonque), an oral RAS(ON) multi-selective inhibitor, for the treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have received at least 1 prior systemic therapy and are not candidates for multiagent systemic therapy, according to a news release from the FDA.1 The approval is based on findings from the phase 3 RASolute 302 trial (NCT06625320), which compared daraxonrasib with standard chemotherapy in this patient population.
The application was reviewed under the FDA Commissioner’s National Priority Voucher pilot program, which the agency accepted for review on July 22, 2026, with an anticipated review time of 1 to 2 months.2
What’s new in the approval?
“Today’s approval provides a critical new option for patients facing an extraordinarily difficult and historically hard-to-treat cancer. It is our fundamental duty to deliver more cures and meaningful treatments to patients as quickly as possible,” stated acting FDA Commissioner Kyle Diamantas, JD, in the press release.1 “I am immensely proud of the dedicated FDA scientists whose fast, thorough review and relentless commitment made this groundbreaking milestone a reality.”
“This drug showed unprecedented results in an area of high unmet need,” said Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence.1 “The approval was granted 6.5 months before the user fee deadline, demonstrating the FDA’s commitment to accelerating the approval of new cancer treatments for patients with serious and life-threatening conditions.”
What data supported the FDA approval of daraxonrasib?
In RASolute 302, daraxonrasib produced a median overall survival (OS) of 13.2 months (95% CI, 10.0-not estimable) compared with 6.6 months (95% CI, 5.4-8.2) with investigator’s choice chemotherapy in patients with RAS G12–mutated PDAC (HR, 0.40; 95% CI, 0.30-0.54; P <.0001).3,4 In the overall population, which included patients with and without an identified tumor RAS mutation, median OS was also 13.2 months with daraxonrasib vs 6.7 months with chemotherapy (HR, 0.40; 95% CI, 0.30-0.53; P <.0001).
These findings were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, and simultaneously published in the New England Journal of Medicine.
The median progression-free survival (PFS) by blinded independent central review was 7.3 months (95% CI, 6.3-8.1) with daraxonrasib vs 3.5 months (95% CI, 2.9-3.8) with chemotherapy in the RAS G12–mutant population (HR, 0.45; 95% CI, 0.34-0.59). In the overall population, it was 7.2 months vs 3.6 months, respectively (HR, 0.49; 95% CI, 0.38-0.64). The confirmed objective response rate favored daraxonrasib over chemotherapy in the RAS G12–mutant population (33.2% vs 11.8%; P <.0001) and overall population (31.6% vs 11.2%; P <.0001).
Daraxonrasib also significantly delayed time to deterioration in cancer-related pain (9.2 vs 3.8 months; HR, 0.51; 95% CI, 0.37-0.71; P <.0001) and in global health status/quality of life (5.7 vs 2.6 months; HR, 0.60; 95% CI, 0.46-0.79; P = .0002) compared with chemotherapy.
How was the RASolute 302 trial designed?
RASolute 302 enrolled 500 adult patients with metastatic PDAC which previously received 1 prior fluoropyrimidine- or gemcitabine-containing regimen, an ECOG performance status of 0 or 1, and documented tumor RAS mutational status. They were randomly assigned in a 1:1 ratio to receive oral daraxonrasib at 300 mg once daily (n = 248) or investigator’s choice of 1 of 4 cytotoxic chemotherapy regimens (n = 252).
Patients were stratified by ECOG performance status, metastatic disease at diagnosis, liver metastases at baseline, and tumor RAS mutational status. The dual primary end points were OS and PFS in the RAS G12–mutant population; secondary end points included OS and PFS in the overall population, objective response rate, and time to deterioration in patient-reported outcomes.
What is daraxonrasib and how does it work?
Daraxonrasib (RMC-6236) is an oral, noncovalent tri-complex inhibitor that suppresses RAS signaling by blocking the interaction between wild-type and mutant RAS(ON) proteins and their downstream effectors. It binds intracellular cyclophilin A to engage GTP-bound RAS mutations, including G12, G13, and Q61 variants, as well as RAS wild-type.
In an interview with CancerNetwork®, Frank McCormick, PhD, FRS, DSc (Hon), a professor in the Helen Diller Family Comprehensive Cancer Center and David A. Wood Distinguished Professor of Tumor Biology and Cancer Research at the University of California San Francisco, said, “It uses a cellular protein to help bring RAS together with the drug, so the drug has a helper to make the whole complex work; it’s a slightly different mechanism of action. It does target the “on” state, which is also true of the next generation of direct KRAS lipids we developed for pancreatic cancer.”
What is the safety profile of daraxonrasib?
Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 43.6% of patients who received daraxonrasib vs 57.5% of those who received chemotherapy; serious TRAEs occurred in 10.8% vs 18.7%, respectively. TRAEs led to discontinuation in 1.2% of patients on daraxonrasib vs 11.2% of those on chemotherapy. The most common any-grade TRAEs with daraxonrasib were rash (85%), diarrhea (58%), stomatitis (53%), nausea (46%), and vomiting (37%).
[Confirm final label safety information, boxed warning status, and any post-marketing requirements once FDA prescribing information is published.]
What other regulatory and guideline developments support daraxonrasib in PDAC?
Previously, the FDA permitted an expanded access program for daraxonrasib in previously treated metastatic PDAC in May 2026.5 In July 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use began a phased review of the agent.6 In August 2026, the European Society for Medical Oncology issued a Clinical Practice Guideline Express Update recommending daraxonrasib monotherapy after chemotherapy progression in patients with RAS G12–mutated metastatic PDAC and an ECOG performance status of 0 or 1.7
Currently, daraxonrasib is being evaluated in the phase 3 RASolute 303 trial (NCT07491445), alone and in combination with gemcitabine plus nab-paclitaxel vs standard of care chemotherapy, as first-line treatment for patients with metastatic PDAC.8 Additionally, the phase 3 RASolute 304 trial (NCT07252232) is evaluating daraxonrasib vs standard of care observation in patients with resected PDAC who have completed neoadjuvant/adjuvant chemotherapy.9
References
- FDA Approves First in Class Targeted Therapy for Metastatic Pancreatic Cancer. News release. FDA. August 26, 2026. Accessed August 26, 2026. https://tinyurl.com/4dt6cwnv
- Revolution Medicines’ new drug application for daraxonrasib accepted for review by US FDA for previously treated metastatic pancreatic cancer. News release. Revolution Medicines, Inc. July 22, 2026. Accessed August 21, 2026. https://tinyurl.com/2c3em84c
- O’Reilly EM, Wainberg ZA, Hendifar AE, et al; RASolute 302 Trial Investigators. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. 2026;395(4):325-337. doi:10.1056/NEJMoa2605555
- Wolpin BM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5
- FDA permits expanded access for investigational pancreatic cancer drug. News release. FDA. May 1, 2026. Accessed August 21, 2026. https://tinyurl.com/4xbhx3pd
- European Medicines Agency expedites assessment of Revolution Medicines’ daraxonrasib under phased review process. News release. Revolution Medicines, Inc. July 7, 2026. Accessed August 21, 2026. https://tinyurl.com/4c6cmxcu
- Conroy T, Ducreux M; on behalf of the ESMO Guidelines Committee. ESMO Clinical Practice Guideline Express Update on daraxonrasib in the treatment of metastatic pancreatic cancer. Ann Oncol. Published online 2026. doi:10.1016/j.annonc.2026.08.003
- Study of daraxonrasib and daraxonrasib + GnP as first-line treatment in patients with metastatic pancreatic adenocarcinoma (RASolute 303). ClinicalTrials.gov. Updated August 18, 2026. Accessed August 21, 2026. https://tinyurl.com/3sh4xsmk
- Study of daraxonrasib (RMC-6236) in patients with resected pancreatic ductal adenocarcinoma (PDAC) (RASolute 304). ClinicalTrials.gov. Updated July 31, 2026. Accessed August 21, 2026. https://tinyurl.com/3svf4fzz
