Phase 23 Trial Comparing Datopotamab Deruxtecan Plus Carboplatin or Cisplatin to Gemcitabine Plus Carboplatin or Cisplatin in Adults with Advanced or Metastatic Urothelial Carcinoma After Prior EV and Pembrolizumab Treatment

What this Trial Is About

Researchers are evaluating treatments for adults with locally advanced or metastatic urothelial carcinoma bladder cancer who have progressed after prior therapy with enfortumab vedotin EV plus pembrolizumab. This global, multicenter, randomized, open-label Phase 23 trial compares a new drug, Datopotamab Deruxtecan Dato-DXd combined with either carboplatin or cisplatin, against the standard gemcitabine combined with carboplatin or cisplatin. The study aims to identify the recommended dose for Phase 3 and assess preliminary safety and efficacy during Part A, followed by a larger Phase 3 evaluation. Participants in Part A receive Dato-DXd at doses of 4 mgkg or 6 mgkg with platinum chemotherapy every three weeks. In Part B, participants receive the selected recommended dose of Dato-DXd or gemcitabine, each combined with either carboplatin or cisplatin, administered intravenously every three weeks. The specific platinum drug and dosing schedule are based on eligibility and investigator judgment, including options for split-dose cisplatin in certain cases. During the trial, participants undergo regular assessments including imaging scans to monitor tumor response, safety evaluations, and laboratory tests. The primary outcomes include overall response rate in Phase 2 and progression-free survival and overall survival in Phase 3, tracked up to approximately 34 to 38 months. Participants are followed throughout treatment and for a period afterward to evaluate treatment effects and safety under medical supervision.

Study of Datopotamab Deruxtecan Plus Carboplatin or Cisplatin Versus Gemcitabine Plus Carboplatin or Cisplatin in Participants With Locally Advanced or Metastatic Urothelial Carcinoma