Summary

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.

Age: 18 Years and older

Gender: All

Start Date: 07/15/2024

Primary Completion Date (Estimated): 07/30/2027

Study Completion Date (Estimated): 12/30/2027

Accepts Healthy Volunteers: No

Trial Purpose and Description

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.

Eligibility Criteria

Age: 18 Years and older

Gender: All

Accepts Healthy Volunteers: No

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