Study Investigating Intravesical HDAC Inhibition to Improve Response to Immuno-Oncology Agents

Inclusion Criteria: * Patients must have histologically confirmed MIBC (T2-T4a, N0, M0 per American Joint Commission on Cancer \[AJCC\]) pure or mixed histology urothelial carcinoma. * Patients must be ineligible for cisplatin-based chemotherapy due to any of the following: Creatinine clearance (CrCl) \< 60 mL/min by the Cockcroft-Gault formula; Hearing impaired ≥ Grade 2 by CTCAE criteria; Neuropathy ≥ Grade 2 by CTCAE criteria; Heart failure NYHA ≥ III; ECOG ≥ 2. * Patients must be medically fit for TURBT and radical cystectomy (RC * Age ≥ 18 years * Body weight \>30 kg * Ability to understand and willingness to sign IRB-approved informed consent. * Willing to provide tumor tissue, blood, and urine samples for research. * ECOG performance status 0 or 1 (Karnofsky ≥80%). * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Participants must have adequate organ and marrow function as defined below: Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1500/mcL; Platelet count ≥100,000/mcL;…