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Original Article �Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer

Eileen M. O’Reilly, M.D., Zev A. Wainberg, M.D., Andrew E. Hendifar, M.D., Mitesh J. Borad, M.D., Filippo Pietrantonio, M.D., Shubham Pant, M.D., Pascal Hammel, M.D., Chiara Cremolini, M.D., Ph.D., Gulam A. Manji, M.D., Ph.D., Paul E. Oberstein, M.D., Ignacio Garrido-Laguna, M.D., Ph.D., Christoph Springfeld, M.D., Ph.D., Nilofer S. Azad, M.D., Makoto Ueno, M.D., Ph.D., Stephen Y. Chui, M.D., Ying Zhang, Ph.D., Hina Patel, Pharm.D., Yeonju Lee, Ph.D., Zeena Salman, M.P.H., Brian M. Wolpin, M.D., M.P.H., for the RASolute 302 Trial Investigators

N Engl J Med

Volume 395(4):325-337

July 23, 2026

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Among patients with previously treated metastatic pancreatic ductal adenocarcinoma, the RAS(ON) inhibitor daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy.

Study Overview

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Randomization and Follow-up.

O’Reilly EM et al. N Engl J Med2026;395:325-337

Figure 1 Randomization and Follow-up. Among the 45 patients who underwent randomization but never received a dose of the trial treatment, data on deaths were obtained for 7 of the 7 patients (100%) in the daraxonrasib group and for 27 of the 38 patients (71.1%) in the chemotherapy group; 5 of 38 patients (13.2%) in the chemotherapy group continued to be followed for survival at the time of data cutoff (February 10, 2026). One patient (0.4%) in the daraxonrasib group and 3 patients (1.2%) in the chemotherapy group, in which patients received chemotherapy of the investigator’s choice, discontinued treatment for reasons other than those listed. Discontinuation of treatment owing to disease progression was documented on the basis of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Symptomatic deterioration leading to discontinuation of treatment was documented by the investigator as discontinuation because of clinical progression (i.e., the patient did not meet the criteria for progressive disease according to RECIST, version 1.1) and not because of an adverse event. The efficacy analyses were based on data from all the patients who had undergone randomization. The safety analyses were based on data from all the patients who received at least one dose of the trial treatment. mPDAC denotes metastatic pancreatic ductal adenocarcinoma.

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Overall Survival.

O’Reilly EM et al. N Engl J Med2026;395:325-337

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Progression-free Survival.

O’Reilly EM et al. N Engl J Med2026;395:325-337

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Demographic and Baseline Disease Characteristics (RAS G12 Population and Overall Population).

O’Reilly EM et al. N Engl J Med2026;395:325-337

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Adverse Events (Safety Population).

O’Reilly EM et al. N Engl J Med2026;395:325-337

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Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy.

Conclusions