Durvalumab And Radiation Therapy Followed by Adjuvant Durvalumab in Patients With Urothelial Cancer (T2-4 N0-2 M0) of the Bladder

OUTLINE: This is a multi-center study. The phase Ib study will evaluate the safety of combining durvalumab with RT followed by adjuvant durvalumab. The phase II study will estimate the Progression Free Survival (PFS) and Disease Control Rate (DCR) with durvalumab plus RT followed by single agent durvalumab for patients with UC of bladder. PHASE Ib INVESTIGATIONAL TREATMENT: Cohort 1 will consist of up to 6 patients who will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will be started on day 1; RT will be started on day 1 or 2. Three patients will be enrolled initially. If 2 or more patients (out of 3) experience dose-limiting toxicity (DLT), the combined treatment will be considered unsafe. Otherwise, an additional 3 patients will be treated at the same dose. If 0 or 1 patient experience DLT, the dose of durvalumab will be deemed safe for phase 2 part of the study. If, however, 2 or more patients (out of 6) experience DLT, the combined treatment will be considered unsafe. Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab treatment will be started 3-4 weeks post completion of durvalumab and RT. PHASE II INVESTIGATIONAL TREATMENT: Subjects will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab monotherapy will be started 3-4 weeks post completion of durvalumab and RT. Life expectancy of \>6 months per treating physician. Adequate organ and marrow function as defined below: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (\> 1500 per mm\^3) 3. Platelet count ≥ 100 x 10\^9/L (\>100,000 per mm\^3) 4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. 5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN. 6. Serum creatinine CL\>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: