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.
Authors: Dingwei Ye, Shusuan Jiang, Fang Yuan, Fangjian Zhou, Kui Jiang, Xiaoping Zhang, XingYa Li, Lasika C. Seneviratne, Guohua Yu, Mingjun Zhang, Shuang Zhang, Mei Chen, Gideon Michael Blumenthal, Omobolaji Oyekunle Akala, Yaling Li, Dian Jing, Junyou Ge, Yanxia Shi
Journal: Journal of Clinical Oncology (2025)

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, respectively; most pts were Asian (81.8%; 100%). Median follow-up was 9.5 mo (range, 7.5–16.2) and 11.7 mo (range, 7.8–17.4), respectively. By data cutoff, 7 (63.6%) and 29 (76.3%) pts, respectively, had discontinued treatment mostly due to PD (45.5%; 55.3%). Treatment-related grade ≥3 AEs occurred in 29/49 (59.2%) of pts, the most common (≥20%) of which were anemia (38.8%) and decreased neutrophil count (28.6 %). No treatment-related deaths were reported by safety data cutoff (May 21, 2024). Efficacy outcomes are shown in the Table. Conclusions: sac-TMT monotherapy had promising antitumor activity in pts with advanced UC who progressed on 1L platinum-based therapy. Clinical trial information: NCT04152499 . Outcome UC 2Lsac-TMT 5 mg/kg (n=11) UC 3L+sac-TMT 5 mg/kg(n=38) Confirmed ORR a n (%) 5 (45.5) 10 (26.3) 95% CI 16.7–76.6 13.4–43.1 CR n (%) 1 (9.1) 0 PR n (%) 4 (36.4) 10 (26.3) SD n (%) 3 (27.3) 17 (44.7) PD n (%) 2 (18.2) 10 (26.3) Not evaluable n (%) 1 (9.1) 1 (2.6) Median DOR b , months (range) NE (3.48+ to 13.86+) NE (2.10 to 14.95+) Median PFS b , months (95% CI) 5.78 (1.68–NE) 5.03 (3.52–7.39) Median OS b , months (95% CI) NE (2.0–NE) 11.5 (8.9–NE) NE, not evaluable. “+” indicates no progressive disease or death as of last disease assessment. a Includes all pts as-treated, and percentages are based on number of pts in each subgroup. b Based on Kaplan-Meier method for censored data.