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

A Phase II, Open-label, Multi-cohort, Multicenter Study in Patients With Unresectable Hepatocellular Carcinoma and Child-pugh B7 and B8 Cirrhosis

The purpose of this study is to assess the safety of atezolizumab and bevacizumab, or atezolizumab alone, as first-line treatment in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC) with Child-pugh B7 or B8 cirrhosis.

This is a Phase II, open-label, multicohort, multicenter study in participants with unresectable, locally advanced, or metastatic HCC who have Child-pugh B7 or B8 liver cirrhosis and have received no prior systemic therapy in this treatment setting. The study is designed to non-comparatively evaluate the safety of atezolizumab plus bevacizumab (Cohort A) or atezolizumab monotherapy (Cohort B) in this population.

General Inclusion 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 Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group (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 10^9 per liter (/L) (≥1000 per microliter [/μL]) without granulocyte colony-stimulating factor support
• Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
• Hemoglobin ≥ 80 grams per liter (g/L) (8 grams per deciliter [g/dL]) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN)
• Serum bilirubin ≤ 3 × ULN
• Creatinine clearance ≥ 50 milliliters per minute (mL/min) (calculated using the Cockcroft-gault formula)
• Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
• International normalized ratio (INR) ≤2.3

General Exclusion Criteria:

• Pregnancy or breastfeeding
• Prior treatment with cluster of differentiation 137 (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: one large volume paracentesis prior to enrollment with diuretic controlled ascites is allowed.
• Participants with ascites controlled on diuretics are allowed
• History of spontaneous bacterial peritonitis within last 12 months