A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Participants With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis

Eligibility Criteria

• * Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
• * Disease that is not amenable to curative surgical and/or locoregional therapies
• * No prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
• * Measurable disease (at least one untreated target lesion) according to RECIST v1.1
• * ECOG Performance Status of 0-2 within 7 days prior to initiation of study treatment
• * Child-Pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
• * Adequate hematologic and end-organ function
• * Life expectancy of at least 12 weeks
• * Female participants of childbearing potential must be willing to avoid pregnancy and egg donation
• * Absolute neutrophil count ≥1.0 x 109/L (≥1000/μL) without granulocyte colony-stimulating factor support
• * Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
• * Hemoglobin ≥ 80 g/L (8 g/dL) AST and ALT ≤ 5 × upper limit of normal (ULN)
• * Serum bilirubin ≤ 3 × ULN
• * Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
• * Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
• * INR ≤2.3
• * Pregnancy or breastfeeding
• * Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• * Treatment with investigational therapy within 28 days prior to initiation of study treatment
• * Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
• * Treatment with systemic immunostimulatory agents
• * Treatment with systemic immunosuppressive medication
• * Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
• * Inadequately controlled hypertension
• * 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 on screening chest computed tomography (CT) scan
• * Participants who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation.
• * Participants on preventative hormonal therapies (i.e., tamoxifen and other hormonal inhibitors) are not excluded.
• * Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
• * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• * Prior allogeneic stem cell or solid organ transplantation
• * Actively listed for liver transplantation
• * Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
• * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
• * A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
• * Grade ≥3 hemorrhage or bleeding event within 6 months prior to initiation of study treatment
• * Hepatic encephalopathy is allowed if no active symptoms or stable within 3 months of study treatment
• * History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS) is excluded from Cohort A only. TIPS is acceptable in Cohort B.
• * Diagnostic Paracentesis is allowed. Therapeutic Paracentesis within 3 months is an exclusion criteria
• * Participants with ascites controlled on diuretics are allowed.
• * History of spontaneous bacterial peritonitis within last 12 months