Multicenter phase 1-2 trial of sacituzumab tirumotecan for advanced or metastatic urothelial carcinoma after chemotherapy and ICIs

TROP2 is overexpressed in advanced or metastatic urothelial carcinoma (A/M UC). Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed antibody-drug conjugate. Cohort 9 of the phase 1-2 2870-001/KL264-01 study evaluated sac-TMT 5 mg/kg monotherapy every two weeks in patients with A/M UC who had disease progression on one or more prior lines of platinum-based chemotherapy and anti-PD-(L)1 therapy. By data cutoff after median follow-up of 18.8 months, 49 patients had received sac-TMT; 37 (76%) had received two or more prior lines of therapy. The confirmed objective response rate was 31% (95% CI 18-45) and the disease control rate was 71% (57-83). Median duration of response was not reached (range 2-1-22.2+ months) and the 12-month probability of sustained response was 53%. Median progression-free survival and overall survival were 5.5 (95% CI 3.6-7.2) months and 12.1 (9.9-15.3) months with 18-month rates of 26% and 33%, respectively. Grade 3 or 4 treatment-related adverse events occurred in 63% of patients; there were no grade 5 TRAEs or febrile neutropenia events. The authors conclude that sac-TMT demonstrated promising antitumor activity in patients with pretreated A/M UC, with a manageable safety profile.