Perlmutter Cancer Center

This is a randomized, open-label, multicenter, Phase 2 clinical study of intravesical gemcitabine delivered via the TAR-200 drug-device combination product in combination with neoadjuvant IV cetrelimab and neoadjuvant IV cetrelimab alone in participants with muscle-invasive urothelial carcinoma of the bladder (clinically referred to as MIBC [muscle invasive bladder cancer]) who are scheduled for RC and are ineligible for or refusing platinum-based neoadjuvant chemotherapy. The transurethral resection of bladder tumor (TURBT) demonstrating an initial pathologic diagnosis of cT2-T4a MIBC must have been completed within 120 days of randomization. All enrolled participants who have confirmed MIBC with absence of nodal or metastatic disease at screening and have met all eligibility criteria will be randomly assigned (5:3) to receive intravesical TAR-200 + IV cetrelimab (Cohort 1) or IV cetrelimab alone (Cohort 2). Two stratification factors for analysis will be completeness of TURBT (visibly complete vs incomplete and =3 cm) and tumor stage (cT2 vs. cT3-4a) at initial diagnosis. Participants must have tumor volume =3 cm prior to randomization. Participants in screening must undergo a cardiovascular risk assessment based on available guidelines for cardiac and surgical risk assessment and must not be enrolled if not considered eligible for RC.