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 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 an 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). The 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%-56%), with a median duration of response of 8.2 months (95% CI, 3.8-not evaluable).⁴

Clinical Perspective on the Approval

Pashtoon Kasi, MD, MS, medical director of gastrointestinal medical oncology at City of Hope Orange County in Irvine, California, said the approval represents an important advance for patients with metastatic pancreatic cancer. City of Hope participated in the pivotal phase 3 trial and has also provided daraxonrasib through the FDA expanded access program.

“Today’s approval of daraxonrasib represents an important advance for patients with metastatic pancreatic cancer, a disease that has remained extraordinarily challenging to treat,” Kasi said in a statement provided to Pharmacy Times. “My patients are responding well, underscoring the importance of daraxonrasib in clinical practice.”

Kasi added that the clinical findings demonstrate that targeting RAS can translate into meaningful improvements in outcomes for patients with pancreatic cancer. He said the approval also reinforces continued investigation of RAS-directed therapies across pancreatic cancer and other RAS-driven malignancies.

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) multiselective, tricomplex 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% of patients 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 Rasonque include rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.¹

Courtney Cavalieri, PharmD, BCOP, clinical oncology pharmacist at Huntsman Cancer Institute at the University of Utah, described the approval as highly anticipated, particularly because patients with PDAC have limited treatment options after progression on earlier therapy.

“Daraxonrasib has demonstrated promising survival benefits, and the availability of an oral therapy that patients can take at home further adds to its appeal,” Cavalieri said in comments provided to Pharmacy Times.

Despite those benefits, Cavalieri emphasized that daraxonrasib is associated with clinically relevant toxicities that require proactive management. Rash, stomatitis, nausea, and diarrhea were among the more commonly reported adverse effects in clinical trials, and trial protocols incorporated specific prophylactic and management strategies, particularly for rash and stomatitis. Cavalieri noted that these recommendations are expected to be reflected in the prescribing information and should be familiar to clinicians incorporating the therapy into practice.

“Oncology pharmacists can play a vital role in setting patients up for success by educating both patients and other health care providers about these supportive care strategies and the importance of early toxicity recognition and management,” Cavalieri said.

That role may extend beyond initial counseling. Pharmacists can help reinforce supportive care plans, assess adherence to an oral regimen, identify toxicities before they worsen, and communicate with the broader oncology team when treatment modifications or additional supportive measures are needed. These responsibilities may be particularly important for helping patients remain on therapy safely and successfully.

Daraxonrasib is also being evaluated in the first-line metastatic setting and in earlier stages of PDAC, raising the possibility that its place in the pancreatic cancer treatment landscape could continue to expand.

“Clinicians who plan to incorporate this therapy into practice should be well informed about both its potential benefits and the supportive care considerations necessary to optimize treatment,” Cavalieri said. “Daraxonrasib represents an exciting new chapter in PDAC treatment, and oncology pharmacists will be essential to helping patients not only access this therapy but stay on it safely and successfully.”

REFERENCES

1. FDA approves first in class targeted therapy for metastatic pancreatic cancer. FDA. 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. 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. Study of daraxonrasib and daraxonrasib plus GnP as first-line treatment in patients with metastatic pancreatic adenocarcinoma (RASolute 303). ClinicalTrials.gov. Updated August 18, 2026. Accessed August 26, 2026. https://clinicaltrials.gov/study/NCT07491445