Efficacy and safety of sacituzumab tirumotecan monotherapy in patients with advanced urothelial carcinoma who progressed on or after prior anti-cancer therapies: Report from the phase 1/2 MK-2870-001 study.

作者：Dingwei Ye, Shusuan Jiang, Yuan Fang, Fangjian Zhou, Kui Jiang, Xiaoping Zhang, XingYa Li, Lasika Seneviratne, Guohua Yu, Mingjun Zhang, Shuang Zhang, Mei Chen, Gideon M. Blumenthal, Omobolaji O. Akala, Yaling Li, Dian Jing, Junyou Ge, Yanxia Shi · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.5_suppl.796 · 被引用次数：12 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Urinary and Genital Oncology Studies

796 Background: Sacituzumab tirumotecan (sac-TMT; also known as MK-2870/SKB264) is a TROP2 targeting ADC with a hydrolytically cleavable linker and a topoisomerase I inhibitor payload, KL610023 (average drug-to-antibody ratio, 7.4). In patients (pts) with urothelial carcinoma (UC), treatment with the anti-TROP2 ADC sacituzumab govitecan led to treatment-related grade ≥3 neutropenia in 35% of pts and febrile neutropenia in 10%. Cohort 9 of the MK-2870-001 (KL264-01; NCT04152499) evaluated sac-TMT monotherapy in pts with unresectable, locally advanced/metastatic UC who progressed on or after prior anti-cancer treatments. Methods: Eligible pts were ≥18 y, had histologically or cytologically confirmed locally advanced/metastatic UC, and had experienced PD on ≥1 prior line of platinum-based therapy. Platinum ineligible pts were eligible if they received prior anti-PD-(L)1 therapy; prior neoadjuvant/adjuvant therapy was counted as a line of therapy if pts progressed ≤12 mo of last dose. Pts must have ECOG PS of ≤1 and measurable disease by CT/MRI. Pts received sac-TMT 5 mg/kg Q2W until PD, unacceptable toxicity, or withdrawal of consent. Primary objective was ORR per RECIST v1.1 by investigator. Secondary objectives included DOR, PFS, OS, and safety. Results: 49 pts were treated by data cutoff (Jun 30, 2024) with a minimum follow-up of ≥9 wk (11 pts received sac-TMT as a second-line treatment; 38 received sac-TMT as a third-line or later treatment). Median age was 62 and 61 y, resp...