Admin_Adham
Jump to Key Points The FDA has approved the first RAS-targeted therapy for metastatic pancreatic cancer, offering a new treatment option for patients with previously treated disease.
Daraxonrasib (Rasonque, Revolution Medicines), an oral RAS(ON) once-daily multi-selective inhibitor, is approved for adults with metastatic pancreatic ductal adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.
"This drug showed unprecedented results in an area of high unmet need," Angelo de Claro, MD, director of the FDA's Oncology Center of Excellence, said in the FDA announcement.
In the randomized, open-label, phase 3 RASolute 302 trial involving 500 patients with previously treated metastatic pancreatic adenocarcinoma, daraxonrasib nearly doubled median overall survival compared with standard chemotherapy (median, 13.2 months vs 6.7 months).
- FDA approved first RAS-targeted therapy for metastatic pancreatic ductal adenocarcinoma.
- Indicated after ≥1 prior systemic therapy or if not candidate for multiagent therapy.
- Phase 3 RASolute 302: OS 13.2 vs 6.7 months vs chemo.
- Daraxonrasib ↑ PFS, response rate; delayed pain/QOL deterioration.
- Grade ≥3 AEs 43.6%; rash, stomatitis common; discontinuation 1.2%.
The drug also roughly doubled progression-free survival, nearly tripled the response rate, and delayed deterioration in both pain and quality of life. The benefit was observed in the overall study population as well as in patients with RAS G12-mutated tumors.
Treatment-related adverse events of grade 3 or higher occurred in 43.6% of patients receiving daraxonrasib and 57.5% receiving chemotherapy in RASolute 302. The most frequent grade 3 or higher events with daraxonrasib were rash (13.7%) and stomatitis (12.0%). Treatment discontinuation due to adverse events occurred in 1.2% of patients taking daraxonrasib compared with 11.2% receiving chemotherapy.
"Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer," said lead investigator Brian Wolpin, MD, MPH, with Dana-Farber Cancer Institute in Boston, in presenting the findings at the American Society of Clinical Oncology (ASCO) 2026.
ASCO invited discussant Jennifer Knox, MD, medical oncologist at Princess Margaret Cancer Center in Toronto, called daraxonrasib a game changer, describing the drug as "probably the most exciting strategy in five decades" for pancreatic cancer.
The FDA had previously issued a "safe to proceed" letter allowing Revolution Medicines to initiate an expanded-access treatment protocol for daraxonrasib before approval.
Daraxonrasib received breakthrough therapy and orphan drug designations as well as priority review. The FDA said the approval was granted 6.5 months before its user fee deadline.
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. The recommended dose of daraxonrasib is 300 mg orally once daily until disease progression or unacceptable toxicity.
