A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-based Treatment Combinations in Patients With Locally Advanced or Metastatic Urothelial Carcinoma After Failure With Platinum-Containing Chemotherapy

Open to people ages 18 years and up

• Histologically documented, locally advanced or metastatic UC (also termed TCC or urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
• Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing
• Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
• ECOG Performance Status of 0 or 1
• Measurable disease (at least one target lesion) according to RECIST v1.1
• Adequate hematologic and end-organ function
• Negative HIV test at screening
• Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV) antibody at screening
• Tumor accessible for biopsy
• For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

• Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
• Eligibility only for the control arm
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled tumor-related pain
• Uncontrolled or symptomatic hypercalcemia
• Symptomatic, untreated, or actively progressing CNS metastases
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Significant cardiovascular disease
• Uncontrolled hypertension
• Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study
• Additional drug-specific exclusion criteria might apply