On August 26, the U.S. Food and Drug Administration (FDA) approved daraxonrasib (Rasonque), an inhibitor of the RAS GTPase family, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.
RASolute 302
Efficacy was evaluated in RASolute 302 (ClinicalTrials.gov identifier NCT06625320), a randomized, open-label, multicenter trial in patients with metastatic pancreatic adenocarcinoma with disease progression after receiving one prior line of systemic therapy. A total of 500 patients were randomly assigned 1:1 to receive either daraxonrasib or physician’s choice of standard of care chemotherapy regimens.
Major efficacy outcome measures were overall survival and progression-free survival as assessed by blinded independent central review in patients with a RAS G12 mutation and in the overall population. Objective response rate was an additional outcome measure.
The trial demonstrated a statistically significant improvement in overall survival, progression-free survival, and objective response rate for patients treated with daraxonrasib compared to standard of care chemotherapy—both in the RAS G12–mutant population and in the overall population.
These findings were presented during the Plenary Session at this year’s ASCO Annual Meeting.
In the overall population, median overall survival was 13.2 months (95% confidence interval [CI] = 10.0 months to not estimable) in the daraxonrasib arm and 6.7 months (95% CI = 5.8–8.0 months) in the standard of care arm (hazard ratio [HR] = 0.40, 95% CI = 0.30–0.53, P < .0001). Median progression-free survival was 7.2 months (95% CI = 5.7–7.5 months) in the daraxonrasib arm and 3.6 months (95% CI = 2.9–4.2 months) in the standard of care arm (HR = 0.49, 95% CI = 0.38–0.64, P < .0001). Objective response rate was 30% (95% CI = 25%–36%) and 11% (95% CI = 7%–15%) in the respective arms (P < .0001).
“I believe daraxonrasib is well positioned to become a new standard of care for adults with metastatic pancreatic cancer who have already received at least one systemic therapy or who are not candidates for multiagent systemic therapy. For decades, despite RAS being the main driver and potential drug target for pancreatic cancer, physicians have largely relied on intravenous cytotoxic chemotherapy to treat this aggressive disease. This approval gives physicians the confidence that directly inhibiting RAS can make a striking difference for patients and provides a critically needed new approach to treating patients with metastatic pancreatic cancer,” said Brian M. Wolpin, MD, MPH, Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School, and principal investigator for the RASolute 302 trial.
The daraxonrasib prescribing information includes warnings and precautions for dermatologic and soft tissue toxicity, stomatitis and oral disorders, diarrhea, gastrointestinal perforation, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.
Recommended Dosage
The recommended daraxonrasib dose is 300 mg orally once daily until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for the concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada; the European Medicines Agency (EMA) and Japan’s Pharmaceuticals and Medical Devices Agency (PDMA) were official observers of this review. The applications may still be under review at the other regulatory agencies.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately 6.5 months ahead of the FDA goal date.
This application is part of the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, which is designed to accelerate the review of products with the potential to address key national priorities. Daraxonrasib received Breakthrough Therapy designation and Orphan Drug designation.
