Daraxonrasib Approved for Metastatic Pancreatic Cancer
The FDA has granted approval to the RAS inhibitor daraxonrasib for adults with metastatic pancreatic ductal adenocarcinoma who have progressed on prior therapy or cannot receive multi-agent regimens.
The U.S. Food and Drug Administration approved the first-in-class RAS inhibitor daraxonrasib (Rasonque) for metastatic pancreatic ductal adenocarcinoma (PDAC). The approval applies to adults with PDAC who have received at least one prior systemic regimen or are ineligible for multi-agent therapy.
Trial Results
The RASolute 302 trial provided the pivotal data for approval. In patients with RAS G12 mutations, second-line daraxonrasib doubled median overall survival (OS) compared with investigator’s choice of chemotherapy: 13.2 versus 6.7 months (P<0.001). Progression-free survival (PFS) also improved more than two-fold: 7.3 versus 3.5 months (P<0.001). The OS and PFS benefits were similar in the overall study population, which included patients with less common RAS mutations.
| Treatment | Median OS (months) | Median PFS (months) |
|---|---|---|
| Daraxonrasib | 13.2 | 7.3 |
| Investigator’s choice | 6.7 | 3.5 |
Detailed patient data can be found in the stats section. For trial design information, see the fixtures page.
Safety Profile
The most common treatment-related adverse event was skin rash, occurring in 85.5% of patients. Grade ≥3 rash and stomatitis were reported in 13.7% and 12% of patients, respectively. Treatment discontinuation due to adverse events occurred in 1.2% of the daraxonrasib arm versus 11.2% of the chemotherapy arm.
Regulatory and Access
Following a preliminary review of the RASolute 302 data, the FDA announced in early May that Revolution Medicines could offer daraxonrasib through an expanded access program in collaboration with authorized prescribers. The approval was granted 6.5 months before the user-fee deadline, underscoring the FDA’s commitment to accelerating new cancer treatments for serious conditions.
"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. "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."
"I've heard this study described as a home run," said Julie Gralow, MD, ASCO chief medical officer, at the ASCO meeting. "I would actually say it's a grand slam."
Rachna Shroff, MD, of the University of Arizona Cancer Center, added that the RASolute 302 results provide proof of principle that targeting the RAS signaling pathway is critical in treating pancreatic cancer. She noted that the study "checks all of the boxes" for relevant and meaningful clinical outcomes.
The drug’s approval marks a significant advance for patients with metastatic PDAC, offering a new standard of care after prior treatment failure or intolerance to multi-agent regimens.
