Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer

Key Inclusion Criteria:

• Patients with histologically or cytologically documented, unresectable, locallyadvanced or metastatic transitional cell carcinoma (transitional cell and mixedtransitional/non-transitional cell histologies) of the urothelium (including renalpelvis, ureters, urinary bladder, and urethra)

• Patients who have not been previously treated with first-line chemotherapy. Patientswho have received prior definitive chemoradiation, adjuvant or neoadjuvant treatmentfor locally advanced disease are eligible provided that progression to locallyadvanced or metastatic disease has occurred >12 months from the last therapy [forchemoradiation and adjuvant treatment] or >12 months from the last surgery [forneoadjuvant treatment].

• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 targetlesion at baseline.

• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG)performance status (PS) of 0 or 1 at enrolment

• Adequate organ and marrow function as defined in the protocol

• Life expectancy ≥12 weeks in the opinion of the investigator

• Evidence of post-menopausal status, or negative urinary or serum pregnancy test forfemale pre-menopausal patients.

Key Exclusion Criteria:

• Prior exposure to immune-mediated therapy (with exclusion of Bacillus CalmetteGuerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, oranti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted.Prior local intervesical chemotherapy or immunotherapy is allowed if completed atleast 28 days prior to the initiation of study treatment.

• No severe concomitant condition that requires immunosuppression medication

• Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis

• Patients who may be eligible for or are being considered for radical resectionduring the course of the study.

• Any medical contraindications to platinum (cisplatin or carboplatin) based doubletchemotherapy and/or known allergy or hypersensitivity to any of the study drugs orany of the study drug excipients