Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): Results from the randomized OptiTROP-Lung03 study.

作者：Li Zhang, Wen‐Feng Fang, XingYa Li, Qiming Wang, Xiangjiao Meng, Wei Zheng, Longhua Sun, Wenxiu Yao, Wu Zhuang, Yun Fan, Minglei Zhuo, Yongzhong Luo, Zhiye Zhang, Xia Song, Runxiang Yang, Jiacheng Yang, Yina Diao, Junyou Ge · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.8507 · 被引用次数：10 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Lung Cancer Research Studies

8507 Background: Sac-TMT (MK-2870/SKB264), a novel TROP2 ADC developed to conjugate a belotecan-derivative topoisomerase I inhibitor, has shown encouraging antitumor activity in EGFRm NSCLC pts in phase Ⅰ trial (Fang et al . AACR 2024). Here, we report the results from a multicenter, randomized, controlled study comparing sac-TMT with docetaxel in previously treated EGFRm NSCLC pts (OptiTROP-Lung03, NCT05631262). Methods: Pts with advanced EGFRm NSCLC who had progressed after EGFR TKI and platinum-based chemotherapy were randomized (2:1) to receive sac-TMT 5 mg/kg Q2W or docetaxel 75 mg/m 2 . Pts with verified progression on docetaxel could be crossed over to receive sac-TMT if eligible. Hierarchical fixed-sequence testing was employed for efficacy endpoints, including ORR (primary) and PFS, assessed by blinded independent review committee (BIRC), followed by OS. Pre-specified OS interim analysis was conducted alongside final PFS analysis, with the level at one-sided alpha of 1.23% determined by alpha spending function. The crossover-adjusted OS was derived using the rank-preserving structural failure time (RPSFT) model. Results: A total of 137 pts (median age 56 yrs; 43.8% male; 82.5% ECOG PS 1; 93.4% prior 3 rd EGFR TKI) were randomized to receive sac-TMT (n=91) or docetaxel (n=46). At a median follow-up of 12.2 mo (data cutoff: Dec 31, 2024), 25.3% of pts (sac-TMT) vs 4.3% (docetaxel) remained on treatment. The study met its primary and key secondary endpoints. Sac-TMT ach...