a study evaluating atezolizumab, with or without bevacizumab, in participants with unresectable hepatocellular carcinoma and child-pugh b7 and b8 cirrhosis

Conditions: Hepatocellular Carcinoma

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.

this is a phase ii, open-label, multicohort, multicenter study in participants with unresectable, locally advanced, or metastatic hepatocellular carcinoma (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:
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 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 general exclusion criteria: * 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

Keywords: cirrhosis liver cancer liver tumor child-pugh b hepatocellular carcinoma atezolizumab bevacizumab immune checkpoint inhibitor digestive system neoplasms kirros ml44719 liver disease genentech immunotherapy cpb cpb 7 cpb 8 tecentriq avastin hcc cirrhotic liver fatty liver