Sacituzumab Tirumotecan in Participants With Advanced or Metastatic Urothelial Carcinoma and Disease Progression after Chemotherapy and Immune Checkpoint Inhibitors
Mené sur 49 patients atteints d'un carcinome urothélial de stade localement avancé ou métastatique (durée médiane de suivi : 18,8 mois), cet essai de phase I/II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du sacituzumab tirumotécan, après l'échec d'au moins un traitement par chimiothérapie et inhibiteurs de point de contrôle immunitaire
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 ≥1 prior line of platinum-based chemotherapy and anti‒PD-(L)1 therapy received sac-TMT 5 mg/kg intravenously every 2 weeks until disease progression, unacceptable toxicity, or participant/physician decision. 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 cutoff (February 17, 2025), 49 participants were treated with sac-TMT; 37 (76%) had received ≥2 prior lines of therapy. Median follow-up for this analysis was 18.8 months. The confirmed ORR was 31% (95% CI, 18%‒45%) and the disease control rate was 71% (95% CI, 57%‒83%). Median DOR was not reached (range, 2.1‒22.2+ months), and the 12-month probability of sustained response was 53%. Median PFS and OS were 5.5 (95% CI, 3.6‒7.2) months and 12.1 (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.
Annals of Oncology , résumé, 2025