FDA Approves Daraxonrasib for Metastatic Pancreatic Cancer

Key Takeaways

• FDA-approved Rasonque (daraxonrasib) is indicated for adults with metastatic pancreatic adenocarcinoma after at least one prior systemic therapy or when they are not candidates for multiagent systemic therapy.
• Median overall survival was longer with daraxonrasib than with standard chemotherapy among previously treated trial participants.
• Common side effects reported for daraxonrasib included rash, diarrhea, and mouth inflammation.

For adults with metastatic pancreatic adenocarcinoma, prior systemic treatment and inability to receive multiagent systemic therapy are distinct clinical circumstances. Daraxonrasib's approved indication includes both, but the circumstances do not define the same evidence base. The difference matters when considering which patients contributed to the efficacy comparison. Investigators focused on adults with metastatic disease who had already received treatment.

Investigators conducted a randomized, open-label, multicenter trial involving 500 adults with previously treated metastatic pancreatic adenocarcinoma. Participants received once-daily oral Rasonque (daraxonrasib), which the Food and Drug Administration (FDA) identifies as a RAS inhibitor, or standard chemotherapy. Enrollment after prior treatment defines the population behind the trial comparison; it does not represent every route into the approved indication.

The FDA reported median overall survival of 13.2 months with Rasonque versus 6.7 months with standard chemotherapy among previously treated participants. The agency listed rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage as the drug's most common side effects. Stomatitis is inflammation of the mouth's mucous membranes. The list describes side effects associated with daraxonrasib, not a comparison of their frequency with chemotherapy.

The FDA granted approval to Revolution Medicines, Inc., after granting Rasonque Breakthrough Therapy and Orphan Drug designations and giving the indication Priority Review. The application also underwent review through the Commissioner's National Priority Voucher pilot program, which the agency describes as a way to accelerate review of therapies addressing national public health priorities. According to the FDA, approval came 6.5 months before the user-fee deadline.

The survival comparison applies to previously treated adults with metastatic pancreatic adenocarcinoma. The FDA announcement does not specify the type of their prior treatment or the disease stage at which they received it. Adults who cannot receive multiagent systemic therapy have another route into the approved indication, but the FDA does not give a separate survival result for that group. The reported comparison therefore cannot supply a survival estimate specific to patients qualifying through that route.

Daraxonrasib is approved for adults with metastatic pancreatic adenocarcinoma after prior systemic therapy or when multiagent systemic therapy is not an option. The reported chemotherapy comparison pertains to previously treated participants, rather than to both eligibility routes.

Clinician Questions

What does daraxonrasib target in metastatic pancreatic adenocarcinoma?

According to the FDA, Rasonque (daraxonrasib) targets multiple forms of the RAS protein, a key driver of tumor growth in most patients with pancreatic adenocarcinoma. The agency does not specify a biomarker-based eligibility criterion.

Was daraxonrasib available through expanded access before FDA approval for metastatic pancreatic adenocarcinoma?

In May, before approving Rasonque (daraxonrasib) for metastatic pancreatic adenocarcinoma, the FDA issued a safe-to-proceed letter allowing Revolution Medicines, Inc. to initiate an expanded-access treatment protocol for the investigational drug under applicable FDA regulations. That permission does not establish that any particular patient received treatment or that expanded access demonstrated efficacy.