Eileen M O’Reilly MD; ASCO 2026: RAS G12 Targeting Drug Daraxonrasib Doubles Survival with Pancreas Cancer in Phase 3 RASolute 302 Study

RAS G12 Targeting Drug Daraxonrasib Doubles Survival with Pancreas Cancer in Phase 3 RASolute 302 Study An interview with: Eileen M O’Reilly MD, Medical Oncologist, Professor of Medicine, Winthrop Rockefeller Chair in Medical Oncology and Leader of the Clinical and Translational Research Program in Pancreas Cancer, Memorial Sloan Kettering Cancer Center, New York, USA CHICAGO, USA—A standing ovation was given at the 2026 ASCO Annual Meeting Plenary Session in response to news reported in a late-breaking abstract (by Brian M. Wolpin MD, MPH from the Dana-Farber Cancer Institute, Gastrointestinal Cancer Center, Boston) of a doubling of median progression-free and overall survival among patients with pancreas cancers randomized to treatment with the multi-selective RAS inhibitor drug daraxonrasib compared with standard of care chemotherapy. The Audio Journal of Oncology heard the details from lead-author of the accompanying article in the New England Journal of Medicine, Eileen M O’Reilly MD, Medical Oncologist, Professor of Medicine, Winthrop Rockefeller Chair in Medical Oncology and Leader of the Clinical and Translational Research Program in Pancreas Cancer, Memorial Sloan Kettering Cancer Center, New York. AUDIO JOURNAL OF ONCOLOGY: Eileen M  O’Reilly MD IN:  [GOODWIN]”I am here at …. OUT:  ………..of Oncology, I’m Peter Goodwin  13:29secs ASCO 2026 Abstract LBA5 Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. ASCO Presenting author: Brian M Wolpin MD MPH, Dana-Farber Cancer Institute, Gastrointestinal Cancer Center, Boston, USA Background: Available 2L therapies offer limited clinical benefit in mPDAC with reported mPFS of 3–4 mo and mOS of 6–7 mo. Aberrant RAS pathway activation is the key driver of PDAC, with oncogenic RAS mutations (mut) identified in >90% of cases, most commonly at codon G12. Daraxonrasib is an oral, RAS(ON) multi-selective, tri-complex inhibitor of the active, GTP-bound state of mutant and wild type RAS. Methods: RASolute 302 (NCT06625320) is a global, randomized, open-label, Ph 3 study in pts with 2L mPDAC and ECOG PS 0-1. Pts were randomized 1:1 to receive daraxonrasib 300 mg PO QD or investigator’s choice of SOC cytotoxic chemo. Dual primary endpoints were OS and PFS by BICR in the RAS G12 mutant (RAS G12) population. Key secondary endpoints included OS and PFS by BICR in the overall population, ORR by BICR in RAS G12 and overall populations. Results: 248 pts were randomized to daraxonrasib and 252 to chemo. Baseline characteristics were balanced between arms. At data cutoff (Feb 10, 2026; mFU: 8.5 mo), all primary and key secondary endpoints were met. Statistically significant, clinically meaningful improvements in OS and PFS were observed with daraxonrasib vs chemo in the RAS G12 and overall populations (Table). Gr ≥3 TRAEs occurred in 43.6% of pts receiving daraxonrasib vs 57.5% receiving chemo. The most common (≥10%) Gr ≥3 TRAEs were rash (13.7%) and stomatitis (12.0%) for daraxonrasib; neutrophil decrease (18.2%) and anemia (16.4%) for chemo. TRSAEs occurred in 10.8% of pts receiving daraxonrasib vs 18.7% receiving chemo. Discontinuation due to TRAEs occurred in 1.2% of pts for daraxonrasib vs 11.2% for chemo. Median/mean daraxonrasib dose intensity was 93.1%/84.7%. Conclusions: Daraxonrasib demonstrated unprecedented improvements in OS and PFS vs chemo in pts with 2L mPDAC with or without an identified tumor RAS mut. Daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals. Results support daraxonrasib as the new SOC for 2L mPDAC. Daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals. Results support daraxonrasib as the new SOC for 2L mPDAC. RAS G12 Overallb Daraxonrasib n=228 Chemo n=231 Daraxonrasib n=248 Chemo n=252   OS Median; mos (95% CI) 13.2 (10.0–NE) 6.6 (5.4–8.2) 13.2 (10.0–NE) 6.7 (5.8–8.0) HR (95% CI) P-value 0.40 (0.30-0.54)