Abstract CT215: RASolve 301: A Phase 3 study of daraxonrasib (RMC-6236) vs. docetaxel in patients with previously treated RAS-mutant NSCLC

作者：Ferdinandos Skoulidis, Kathryn C. Arbour, Sanjay Popat, Colin R. Lindsay, H. Hironouchi, Gérard Zalcman, Alessandra Curioni-Fontecedro, Jarushka Naidoo, Adrianus J. de Langen, Lin Tao, Erica Su, Minoti Hiremath, Achim Rittmeyer, Melissa Johnson · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-ct215 · 被引用次数：2 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies

Abstract Background: Previously treated non-small cell lung cancer (NSCLC) patients represent a significant unmet medical need. After patients have received platinum-based chemotherapy and/or immune checkpoint inhibitors, docetaxel monotherapy is often the mainstay of treatment, with reported objective response rates (ORRs) of 9.2%-14.7%, median progression-free survival (mPFS) of 3.0-4.5 months, and median overall survival (mOS) of 9.1-11.8 months across multiple studies. RAS mutations occur in ∼30% of NSCLC cases, with non-G12C variants making up 60%. The majority of these are G12X mutations (e.g., G12D, G12V, etc.), for which no approved targeted therapies are available.In an ongoing Phase 1 monotherapy trial (NCT05379985), 120-220 mg daily daraxonrasib (RMC-6236), an oral, RAS(ON) multi-selective, tri-complex inhibitor of GTP-bound mutant and wild-type RAS, showed manageable safety and preliminary efficacy in patients with NSCLC. As of a September 30, 2024 data cutoff (N=73), Grade ≥3 treatment-related adverse events (TRAEs) reported in ≥2 patients included rash (n=5, 7%), vomiting (n=2, 3%), and anemia (n=2, 3%), with no Grade 4 or Grade 5 TRAEs. In 40 patients with RAS G12X-mutant NSCLC previously treated with one or two lines of therapy (including immunotherapy and platinum-based chemotherapy), daraxonrasib at 120-220 mg resulted in a confirmed ORR of 38%, median duration of response (DOR) of 15.1 months (95% CI: 11.1, Not Estimable [NE]), mPFS of 9.8 months (95% CI: 6...