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

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 the longest DOR, suggesting that patients may have achieved longer remission duration) months], and the 12-month probability of sustained response was 53%. Median PFS and OS were 5.5 months (95% CI 3.6-7.2 months) and 12.1 months (95% CI, 9.9-15.3 months), with 18-month rates of 26% and 33%, respectively. Grade 3/4 treatment-related adverse events (AEs) occurred in 31 participants (63%), and the most common (≥5%) were anemia (41%), decreased neutrophil count (35%), decreased white blood cell count (20%), stomatitis (12%), and decreased platelet count (8%). There were no grade 5 treatment-related AEs or febrile neutropenia events.

CONCLUSIONS

Sac-TMT 5 mg/kg monotherapy every 2 weeks demonstrated promising antitumor activity in participants with heavily pretreated advanced or metastatic UC, with a manageable safety profile, warranting further evaluation of sac-TMT in this population.