Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin

Inclusion Criteria:

* Histologically or cytologically documented muscle-invasive UC of the bladder.
* Participants with transitional cell and mixed transitional/non-transitional cell histologies;
* Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0 (participants with T1 stage are allowed only with N1 disease)
* Participants should also have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC or bladder UC.
* Medically fit for cystectomy and able to receive neoadjuvant therapy;
* Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;
* ECOG performance status of 0,1,2 at enrollment.
* Availability of tumor sample prior to study entry;
* Must have a life expectancy of at least 12 weeks at randomization.
* Cisplatin-ineligible, following criteria based on Galsky et al 2011 OR Refuse cisplatin based chemotherapy (must be documented in the medical records)

Exclusion criteria:

* Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
* Active infection
* Uncontrolled intercurrent illness
* Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin \[BCG\]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or anti-PD-L2 antibodies.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.