Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

BACKGROUND: mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate-bound state of mutant and wild-type RAS. METHODS: G12 and overall populations. Safety was also assessed. RESULTS: G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group. CONCLUSIONS: Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. (Funded by Revolution Medicines; RASolute 302 ClinicalTrials.gov number, NCT06625320.).

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Publication Details

Journal
New England Journal of Medicine
Published
2026-05-31
DOI
https://doi.org/10.1056/nejmoa2605555
Primary Topic
Pancreatic and Hepatic Oncology Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Zeena Salman, Christoph Springfeld, Zev A. Wainberg, Nilofer S. Azad et al.
New England Journal of Medicine
Pancreatic and Hepatic Oncology Research
article

Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Zeena Salman, Christoph Springfeld, Zev A. Wainberg, Nilofer S. Azad, Chiara Cremolini, Pascal Hammel, Andrew E. Hendifar, Paul E. Oberstein, Hina Patel, Gulam A. Manji, Eileen M. O’Reilly, Makoto Ueno, Mitesh J. Borad, Ying Zhang, Filippo Pietrantonio, Brian M. Wolpin, Stephen Y. Chui, Ignacio Garrido-Laguna, Shubham Pant, Yeonju Lee
article en

Abstract

BACKGROUND: mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate-bound state of mutant and wild-type RAS. METHODS: G12 and overall populations. Safety was also assessed. RESULTS: G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group. CONCLUSIONS: Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. (Funded by Revolution Medicines; RASolute 302 ClinicalTrials.gov number, NCT06625320.).

New England Journal of Medicine
Cedars-Sinai Medical Center (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), University of California, Los Angeles (US), University of Utah (US), Heidelberg University (DE), Université Paris-Saclay (FR), Columbia University Irving Medical Center (US), Huntsman Cancer Institute (US), University Hospital Heidelberg (DE), WinnMed (US), Kanagawa Prefectural Hospital Organization (JP), NYU Langone Health (US), Revolution Medicines (United States) (US), National Center for Tumor Diseases (DE), Dana-Farber Cancer Institute (US), Mayo Clinic in Florida (US), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Sidney Kimmel Comprehensive Cancer Center (US), Hôpital Paul-Brousse (FR), Azienda Ospedaliera Universitaria Pisana (IT), Kanagawa Cancer Center
Revolution Medicines
Good health and well-being
Openalex Percentile: Top 7%
Pancreatic and Hepatic Oncology Research
DOISourceOpenAlex
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