Objective:

To evaluate the efficacy and safety of daraxonrasib, an investigational oral RAS(ON) multi-selective inhibitor, compared to chemotherapy in patients with previously treated metastatic pancreatic cancer.

Key Findings:

• Patients receiving daraxonrasib had a median overall survival of 13.2 months compared to 6.7 months for chemotherapy.
• The hazard ratio for death was 0.40 for daraxonrasib compared to chemotherapy.
• Median progression-free survival was 7.2 months for daraxonrasib versus 3.6 months for chemotherapy.
• Objective response rate was 31.6% for daraxonrasib compared to 11.2% for chemotherapy.
• 33.2% of patients with a known RAS G12 mutation experienced substantial tumor shrinkage with daraxonrasib.

Interpretation:

Daraxonrasib demonstrates significant improvements in overall survival and progression-free survival compared to standard chemotherapy in patients with metastatic pancreatic cancer, regardless of RAS mutation status.

Limitations:

• The trial only included patients who had previously received one line of chemotherapy.
• Long-term effects and overall survival benefits beyond the study duration are yet to be determined.

Conclusion:

Daraxonrasib may represent a new standard of care for second-line treatment of metastatic pancreatic cancer, pending FDA approval.