Gemcitabine/Cisplatin Plus Cemiplimab With or Without Fianlimab in Localized Muscle-invasive Bladder Cancer (NeoSTOP-IT)

This is a phase 2, open-label, randomized trial with continuous toxicity monitoring to ensure safety using Bayesian toxicity monitoring, which will evaluate treatment with doublet platinum-based chemotherapy (gemcitabine and cisplatin) plus cemiplimab (REGN2810) with or without fianlimab (REGN3767) for localized muscle-invasive bladder cancer (MIBC). Participants will be randomized to 4 cycles of 3 weeks each (12 weeks total) with gemcitabine, cisplatin, and cemiplimab with or without fianlimab. Participants achieving a clinical complete response will continue 13 more cycles of immunotherapy (39 weeks total). The total duration of systemic treatment, including neoadjuvant therapy, will be 52 weeks. In addition to the actual time on treatment, there will be time off treatment for recovery after neoadjuvant treatment and before adjuvant treatment. First, between the neoadjuvant phase and cystoscopy (with TURBT for residual disease), there will be up to 4 weeks off treatment. In between the cystoscopy/TURBT and start of adjuvant immunotherapy, there will be an additional up to 4 week interval for recovery. Participants will have regularly scheduled study visits at the clinical site on Day 1 and Day 8 of every three-week cycle in the neoadjuvant setting, where continuous assessment, including treatment response and safety assessments, will be performed. These will include laboratory tests, taking of vital signs, and physical examinations. In the adjuvant setting for participants who continue to maintenance immunotherapy, participants will have regularly scheduled study visits at the clinical site on Day 1 of every three-week cycle. Response to treatment will be determined by three modalities. First, CT scans (chest, abdomen, and pelvis with and without contrast) to ensure no metastatic disease. For participants who are unable to get a CT scan w/ contrast due to renal function (or any other reason), an MRI with and without contrast may be used instead. Scans are required at baseline and every 3 months in the adjuvant setting for participants who continue on with maintenance immunotherapy. Second, all participants will undergo post-treatment cystoscopy every 3 months while on treatment. Third, all participants will undergo post-treatment urine cytology every 3 months while on treatment.