Key Takeaways:
- Daraxonrasib reduced death risk by 60% in metastatic pancreatic cancer
- Median overall survival reached 13.2 months versus 6.6 months for chemo
- Only 1.2% of patients discontinued therapy due to side effects
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Daraxonrasib cuts death risk 60% in pancreatic cancer trial
Revolution Medicines Inc. said its oral RAS inhibitor daraxonrasib reduced the risk of death by 60% in patients with previously treated metastatic pancreatic cancer, meeting all primary and key secondary endpoints in a global Phase 3 trial.
"The data from the Phase 3 RASolute 302 trial clearly validate our pioneering, science-driven approach," Mark A. Goldsmith, chief executive officer and chairman of Revolution Medicines, said in a statement. The results were presented at the American Society of Clinical Oncology annual meeting in Chicago and published simultaneously in the New England Journal of Medicine.
In the 500-patient trial, patients receiving once-daily daraxonrasib achieved a median overall survival of 13.2 months compared with 6.6 months for those on standard-of-care chemotherapy, a hazard ratio of 0.40 (95% CI: 0.30–0.54; p<0.0001). The hazard ratio of 0.40 means daraxonrasib patients had a 60% lower risk of death at any given time versus chemotherapy. Progression-free survival reached 7.3 months versus 3.5 months (HR 0.45), and the objective response rate was 33.2% compared with 11.8%. Results were consistent in the broader intent-to-treat population that included patients without an identified RAS mutation.
Daraxonrasib was generally well tolerated, with grade 3 or higher treatment-related adverse events occurring in 43.6% of patients versus 57.5% for chemotherapy. Only 1.2% of daraxonrasib patients discontinued therapy due to side effects, compared with 11.2% in the chemotherapy arm. Patient-reported outcomes showed daraxonrasib significantly delayed deterioration in pain (HR 0.51) and global health status (HR 0.60).
The results mark a potential shift in treating pancreatic ductal adenocarcinoma, one of the deadliest cancers with a five-year survival rate of about 3%. More than 90% of pancreatic tumors harbor RAS mutations, making them a primary target for RAS(ON) inhibitors like daraxonrasib. Revolution Medicines plans to submit the data to global regulators, including the US Food and Drug Administration under a National Priority Voucher that could accelerate review. The FDA has also authorized an expanded access treatment protocol for eligible patients.
Daraxonrasib is being evaluated in three additional Phase 3 registrational trials, including in earlier lines of pancreatic cancer treatment and in metastatic RAS-mutant non-small cell lung cancer. The company's pipeline also includes mutant-selective RAS inhibitors targeting G12C, G12D, G12V, Q61H, and G13C variants.
This article is for informational purposes only and does not constitute investment advice.
[1] Revolution Medicines Announces ASCO Plenary Presentation Highlighting Unprecedented Results from Pivotal Phase 3 RASolute 302 Clinical Trial of Daraxonrasib in Previously Treated Metastatic Pancreatic Cancer[2] Revolution Medicines Announces Publication in New England ...[3] Revolution Medicines' daraxonrasib data published in NEJM[4] In a phase 1–2 study of daraxonrasib, treatment-related adverse events of grade 3 or higher occurred in 30% of patients with previously treated RAS-mutated pancreatic cancer, and up to 35% of patients had an objective response. Full study results: https://nej.md/4f7xfhX Science behind the Study: Advances in RAS Therapeutics for Pancreatic Cancer https://nej.md/4neOTCE[5] Revolution Medicines Announces ASCO Plenary Presentation Highlighting Unprecedented Results from Pivotal Phase 3 RASolute 302 Clinical Trial of Daraxonrasib in Previously ...
