2026-06-03 コロンビア大学
◆2026年米国臨床腫瘍学会（ASCO）で発表され、同時に『New England Journal of Medicine』に掲載された第Ⅲ相試験（RASolute 302）では、転移性膵管腺がん患者約500人を対象に評価した結果、ダラクソンラシブ投与群の全生存期間中央値は13.2か月となり、化学療法群の6.7か月と比べてほぼ2倍に延長した。また、無増悪生存期間も改善し、死亡リスクを60％低減した。膵臓がんの90％以上はKRAS遺伝子変異によって駆動されるが、KRASは長年「創薬不可能（undruggable）」な標的と考えられてきた。
◆コロンビア大学のKenneth Olive博士らは、独自の高度マウスモデル（Mouse Hospital）を用いて本薬の前臨床評価に貢献した。今回の成果は、膵臓がん治療における数十年ぶりの大きな進歩と評価されており、KRAS標的治療の実用化に向けた重要な転換点となっている。
＜関連情報＞
- https://www.cancer.columbia.edu/news/columbia-research-helps-propel-daraxonrasib-potential-new-standard-care-pancreatic-cancer
- https://www.nejm.org/doi/full/10.1056/NEJMoa2605555
既治療転移性膵臓がんにおけるダラキソンラシブまたは化学療法 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., +13 , for the RASolute 302 Trial Investigators
New England Journal of Medicine Published: May 31, 2026
DOI: 10.1056/NEJMoa2605555
Abstract
Background
Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS 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
In this phase 3, international, open-label, randomized trial, we randomly assigned patients with previously treated mPDAC to receive daraxonrasib or chemotherapy of the investigator’s choice. The dual primary end points were overall survival and progression-free survival in the subpopulation of patients with RAS G12 mutations (the RAS G12 population). Key secondary end points included overall survival and progression-free survival in the overall population (which included patients with RAS G12, G13, or Q61 mutations or with no RAS mutation identified) and objective response and patient-reported quality of life in the RAS G12 and overall populations. Safety was also assessed.
Results
A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS 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.)
