A Study of RO7247669 Alone or in Combination With Tiragolumab vs Atezolizumab in Participants With Untreated Locally Advanced or Metastatic Urothelial Cancer

This study will evaluate the efficacy, safety, and pharmacokinetics of RO7247669 alone or in combination with tiragolumab compared with atezolizumab in participants with previously untreated, locally advanced or metastatic urothelial cancer (mUC) who are ineligible to receive a platinum containing chemotherapy.

Inclusion Criteria:Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urotheliumIneligible ("unfit") to receive platinum-based chemotherapyNo prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma (UC)Measurable disease; at least one measurable lesion as defined by response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)Availability of a representative leftover tumor specimen that is suitable for determination of PD-L1 status as assessed by a central laboratoryAdequate hematologic and end organ functionNegative for hepatitis B and hepatitis C virus (HCV)Adequate cardiovascular functionExclusion Criteria:Pregnancy or breastfeedingGFR <15 mL/min/1.73 m2Symptomatic, untreated, or actively progressing central nervous system (CNS) metastasesHistory of leptomeningeal diseaseUncontrolled tumor-related painUncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage proceduresUncontrolled or symptomatic hypercalcemiaActive or history of autoimmune disease or immune deficiencyHistory of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scanActive tuberculosis (TB) or Epstein-Barr virus (EBV)Significant cardiovascular/cerebrovascular disease within 3 months prior to initiation of study treatmentMajor surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the studyHistory of another primary malignancy other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of malignancies with a negligible risk of metastasis or deathSevere infection within 4 weeks prior to initiation of study treatmentTreatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatmentPrior allogeneic stem cell or solid organ transplantationTreatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment or within 5 months after the final dose of atezolizumab, 4 months after the final dose of RO7247669, or 90 days after the final dose of tiragolumabCurrent treatment with anti-viral therapy for HBVTreatment with any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatmentTreatment with investigational therapy within 28 days prior to initiation of study treatmentPrior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-TIGIT and anti-LAG3 therapeutic antibodies or pathways targeting agentsTreatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatmentTreatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatmentHistory of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins