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 cellhistologies;

• Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladderwith clinical state T1N1M0 (participants with T1 stage are allowed only with N1disease)

• Participants should also have not received prior systemic chemotherapy orimmunotherapy 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 fortreatment 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 Refusecisplatin 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-CalmetteGuerin [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, antiPD-L1, or anti-PD-L2 antibodies.

• Current or prior use of immunosuppressive medication within 14 days before the firstdose of IPs.