A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Participants With High-risk Muscle-invasive Bladder Cancer (MIBC) Who Are ctDNA Positive Following Cystectomy

Inclusion Criteria:

Inclusion Criteria for the Surveillance Phase:

• Histologically confirmed MIUC (also termed transitional cell carcinoma [TCC]) of thebladder

• Tumor, nodes, and metastases (TNM) classification (based on American Joint Committeeon Cancer [AJCC] Cancer Staging Manual, 8th Edition; Amin et al. 2016) atpathological examination of surgical resection specimen as follows: For participantstreated with prior neoadjuvant chemotherapy (NAC): tumor stage of ypT2-4a or ypN+and M0. For participants who have not received prior NAC: tumor stage of pT2-4a orpN+ and M0

• Surgical resection of MIUC of the bladder

• Participants who have not received prior platinum-based NAC must be ineligible forcisplatin-based adjuvant chemotherapy, have refused it, or will not receive it basedon physician's decision

• ctDNA assay developed based on tumor tissue specimen and matched normal DNA fromblood

• Tumor programmed death ligand (PD-L1) expression per immunohistochemistry (IHC) thatis evaluable by central testing of a representative tumor tissue specimen

• Absence of residual disease and absence of metastasis, as confirmed by a negativebaseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of thepelvis, abdomen, and chest no more than 4 weeks prior to enrollment

• Full recovery from cystectomy and enrollment within 24 weeks following cystectomy.Minimum of 6 weeks must have elapsed from surgery

Additional Inclusion Criteria for the Treatment Phase:

• Blood for plasma ctDNA sample evaluated to be ctDNA positive, defined as thepresence of two or more mutations out of the 16 mutations identified based onparticipant' whole exome sequencing (WES) evaluable (ctDNA assay designability)report

• Absence of residual disease and absence of metastasis, as confirmed by a negativebaseline CT or MRI scan of the pelvis, abdomen, and chest no more than 28 days priorto randomization, as assessed by the investigator and Independent Review Facility

• Eastern cooperative oncology group (ECOG) performance status of ≤ 2

• Life expectancy ≥12 weeks

• Adequate hematologic and end-organ function

• For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraception and agreement to refrain fromdonating eggs

Exclusion Criteria:

General Medical Exclusion Criteria for the Surveillance Phase:

• Known PD-L1 IHC result for adjuvant therapy. The decision for the adjuvant therapyshould not be based on the PD-L1 IHC result

• Pregnancy or breastfeeding

• Positive test for human immunodeficiency virus (HIV), with the following exception:Participants with a positive HIV test at screening are eligible provided they arestable on antiretroviral therapy, have a cluster of differentiation 4 (CD4) count ≥ 200 per microliter (/µL), and have an undetectable viral load

• Participants with active hepatitis B virus (HBV) or hepatitis C virus (HCV).Participants with past HBV infection or resolved HBV infection are eligible. Anegative HBV deoxyribonucleic acid (DNA) test must be obtained in these participantsprior to enrollment. Participants positive for HCV antibody are eligible only ifpolymerase chain reaction (PCR) is negative for HCV RNA

• Active tuberculosis (TB) confirmed by a test performed within 3 months prior totreatment initiation

• History of severe allergic, anaphylactic, or other hypersensitivity reactions tochimeric or humanized antibodies or fusion proteins

• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cellsor any component of the atezolizumab formulation

• History of autoimmune disease. Participants with a history of autoimmune-relatedhypothyroidism on a stable dose of thyroid replacement hormone may be eligible forthis study. Participants with controlled type I diabetes mellitus (T1DM) on a stabledose of insulin regimen may be eligible for this study

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-inducedpneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screeningchest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) ispermitted

• Significant cardiovascular disease, such as New York Heart Association cardiacdisease (Class II or greater), myocardial infarction (MI) within the previous 3months, unstable arrhythmias, or unstable angina

Cancer-Specific Exclusion Criteria for the Surveillance Phase:

• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment

• Adjuvant chemotherapy or radiation therapy for UC following cystectomy

• Treatment with any other investigational agent or participation in another clinicaltrial with therapeutic intent within 28 days or 5 half-lives of the drug, whicheveris longer, prior to enrollment

• Malignancies other than UC within 5 years prior to study enrollment

Additional Exclusion Criteria for the Treatment Phase:

• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to randomization to the treatment phase. Hormone-replacement therapyor oral contraceptives are allowed

• Adjuvant chemotherapy or radiation therapy for UC following cystectomy

• Treatment with any other investigational agent or participation in another clinicaltrial with therapeutic intent within 28 days or 5 half-lives of the drug, whicheveris longer, prior to randomization to the treatment phase

• Positive test for HIV, with the following exception: Participants with a positiveHIV test at screening are eligible provided they are stable on antiretroviraltherapy, have a CD4 count ≥200/μL, and have an undetectable viral load

• Participants with active HBV or HCV

• Active tuberculosis confirmed by a test performed within 3 months prior to treatmentinitiation