FDA Approves First-in-Class Daraxonrasib for Metastatic Pancreatic Cancer

The FDA has approved daraxonrasib (Rasonque; Revolution Medicines, Inc.), a first-in-class RAS inhibitor, for adults with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or who are not candidates for multiagent systemic therapy. The approval introduces a targeted oral treatment option for a malignancy in which RAS signaling drives the large majority of tumors.¹

Daraxonrasib is administered orally once daily and targets multiple forms of RAS, a central driver of tumor growth in pancreatic ductal adenocarcinoma (PDAC). The approval was granted approximately 6.5 months ahead of the therapy's user fee deadline, according to the FDA.¹

Phase 3 Trial Shows Significant Survival Improvement

The approval was supported by findings from the international, randomized, open-label phase 3 RASolute 302 trial (NCT06625320), which enrolled 500 patients with previously treated metastatic PDAC. Patients were randomly assigned 1:1 to receive daraxonrasib or investigator-selected standard-of-care chemotherapy.^2,3

In the overall study population, median overall survival (OS) was 13.2 months with daraxonrasib compared with 6.7 months in patients treated with chemotherapy, corresponding to a hazard ratio (HR) for death of 0.40 (P < .001). Median progression-free survival (PFS) was 7.2 months with daraxonrasib and 3.6 months with chemotherapy (HR, 0.49; P < .001).²

Most patients enrolled in RASolute 302 had tumors harboring RAS G12 mutations. Among this population, median OS was 13.2 months with daraxonrasib compared with 6.6 months with chemotherapy (HR, 0.40; P < .001). Median PFS was 7.3 months and 3.5 months, respectively (HR, 0.45; P < .001).²

The findings build on earlier phase 1/2 evidence demonstrating antitumor activity with daraxonrasib in patients with previously treated RAS-mutated PDAC. In that study, patients treated with second-line daraxonrasib at the 300-mg dose who had RAS G12 mutations achieved an objective response rate of 35% (95% CI, 17% to 56%), with a median duration of response of 8.2 months (95% CI, 3.8 to not evaluable).⁴

Targeting a Long-Standing Driver in Pancreatic Cancer

RAS pathway activation has long represented an important therapeutic target in pancreatic cancer. More than 90% of PDAC tumors harbor oncogenic RAS mutations, yet broadly targeting RAS has historically proved difficult. Daraxonrasib is a RAS(ON) multi-selective, tri-complex inhibitor designed to inhibit the active guanosine triphosphate-bound state of mutant and wild-type RAS.^2,4

The FDA approval is particularly notable because pancreatic adenocarcinoma accounts for approximately 90% to 95% of the roughly 67,000 new pancreatic cancer cases diagnosed annually in the United States. The disease is frequently detected after it has advanced and has historically been associated with limited treatment options and poor outcomes.¹

Development of daraxonrasib continues in additional PDAC settings. The phase 3 RASolute 303 trial is evaluating daraxonrasib alone or in combination with gemcitabine and nab-paclitaxel against chemotherapy as a first-line treatment for metastatic pancreatic adenocarcinoma.⁵

Safety and Pharmacist Considerations

In RASolute 302, grade 3 or higher adverse events occurred in 61.8% of patients receiving daraxonrasib compared with 69.6% receiving chemotherapy. Treatment-related adverse events leading to discontinuation occurred in 1.2% and 11.2% of patients, respectively.²

According to the FDA, the most common adverse effects associated with daraxonrasib include rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. These toxicities create an important role for pharmacists in patient education, supportive care, adherence assessment, and early recognition of adverse effects during oral therapy.¹

The approval of daraxonrasib establishes RAS inhibition as a new targeted treatment approach for metastatic pancreatic adenocarcinoma and provides an oral option backed by randomized evidence of improved survival compared with standard chemotherapy.

REFERENCES

1. FDA approves first in class targeted therapy for metastatic pancreatic cancer. News release. FDA. Published August 26, 2026. Accessed August 26th, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-hiv-infection-newborns

2. O'Reilly EM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. 2026;395(4):325-337. doi:10.1056/NEJMoa2605555

3. Phase 3 study of daraxonrasib (RMC-6236) in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) (RASolute 302). ClinicalTrials.gov Identifier: NCT06625320. Last Updated June 2, 2026. Accessed August 26, 2026. https://clinicaltrials.gov/study/NCT06625320

4. Wolpin BM, Park W, Garrido-Laguna I, et al. Daraxonrasib in previously treated advanced RAS-mutated pancreatic cancer. N Engl J Med. 2026;394(18):1790-1802. doi:10.1056/NEJMoa2505783

5. CStudy of daraxonrasib and daraxonrasib plus GnP as first-line treatment in patients with metastatic pancreatic adenocarcinoma (RASolute 303). ClinicalTrials.gov Identifier: NCT07491445. Last Updated August 18, 2026. Accessed August 26, 2026. https://clinicaltrials.gov/study/NCT07491445