Sacituzumab tirumotecan in participants with advanced or metastatic urothelial carcinoma and disease progression after chemotherapy and immune checkpoint inhibitors

作者：Y. Zhu, Shaofeng Jiang, Y. Shi, Shixuan Wang, Fenghong Yuan, Fangjian Zhou, Kui Jiang, Xian Zhang, Lasika Seneviratne, Guan Yu Yu, Mingjun Zhang, Tao Liu, Xin Li, Xi Chen, Xian Wang, Xiaofeng Zhang, Yunpeng Liu, Yuanyuan Ge, Ming Chen, Gideon M. Blumenthal, Omobolaji O. Akala, Y Li, Xiuyang Li, Joy Yang Ge, Dingwei Ye · 发表于：Annals of Oncology · 年份：2025 · DOI：10.1016/j.annonc.2025.11.013 · 被引用次数：5 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Renal cell carcinoma treatment

BACKGROUND: Trophoblast cell-surface antigen 2 (TROP2) is overexpressed in advanced or metastatic urothelial cancer (UC), representing a promising therapeutic target. Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes payload delivery to tumor cells. We present preliminary results for sac-TMT monotherapy from cohort 9 of the phase 1/2 2870-001/KL264-01 study in participants with advanced or metastatic UC. PARTICIPANTS AND METHODS: Eligible participants with locally advanced or metastatic UC and disease progression on one or more prior line of platinum-based chemotherapy and anti-programmed cell death protein 1/programmed cell death-ligand 1 therapy received sac-TMT 5 mg/kg intravenously every 2 weeks until disease progression, unacceptable toxicity, or participant/physician decision. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST version 1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: By data cut-off (17 February 2025), 49 participants were treated with sac-TMT; 37 (76%) had received two or more prior lines of therapy. Median follow-up for this analysis was 18.8 months. The confirmed ORR was 31% [95% confidence interval (CI), 18% to 45%] and the disease control rate was 71% (95% CI 57% to 83%). Median DOR was not reached [range 2.1-22.2+ (+ indicates censored data for th...