Daraxonrasib Transforms Outcomes in Metastatic Pancreatic Cancer: Landmark Phase 3 Trial Doubles Survival
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Pancreatic ductal adenocarcinoma (PDAC) remains one of oncology’s greatest challenges, with dismal prognosis in the metastatic setting and few effective options after initial therapy. Activating RAS mutations—predominantly KRAS G12 variants—drive >90% of PDAC tumors and were long deemed “undruggable.” Daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor targeting the active GTP-bound state of mutant and wild-type RAS, has now delivered the first major targeted-therapy breakthrough in this disease.
In the global Phase 3 RASolute 302 trial, 500 patients with previously treated metastatic PDAC were randomized to oral daraxonrasib (300 mg daily) or investigator’s choice chemotherapy. The dual primary endpoints were overall survival (OS) and progression-free survival (PFS) in the prespecified RAS G12 population (91.8% of enrollees).
#Daraxonrasib doubled median OS to 13.2 months versus 6.6 months with chemotherapy (hazard ratio 0.40; P<0.001). Twelve-month OS nearly tripled, from 18.7% to 53.3%. PFS improved from 3.5 to 7.3 months. Tolerability was markedly better: treatment-related discontinuations occurred in only 1.2% of daraxonrasib recipients versus 11.2% with chemotherapy.
These results, published in the New England Journal of Medicine, establish daraxonrasib as a new standard for previously treated RAS-mutant metastatic PDAC. The convenient oral regimen, combined with a clinically meaningful survival gain and favorable safety profile, offers renewed hope to patients and validates direct RAS inhibition as a viable strategy. This advance is poised to influence therapeutic development across other RAS-driven malignancies.
References ————————-
1. O’Reilly EM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026 May 31. doi:10.1056/NEJMoa2605555
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