Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone

This is a randomized Phase 3 study to determine whether treatment with vaccinia virus based immunotherapy (Pexa-Vec) followed by sorafenib increases survival compared to treatment with sorafenib in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.

Inclusion Criteria: * Histological/cytological diagnosis of primary HCC * Advanced stage HCC (Barcelona Clinic Liver Cancer \[BCLC\] Stage C or B per American Association for the Study of Liver Disease \[AASLD\] guidelines) * At least one measurable viable tumor in the liver, ≥1 cm longest diameter (LD), using a dynamic imaging technique (arterial phase of triphasic computerized tomography \[CT\] scan, or dynamic contrast-enhanced magnetic resonance imaging \[MRI\]), and injectable under imaging-guidance (CT and/or ultrasound) * Child-Pugh Class A * Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale * Adequate hematological, hepatic, and renal function: * Additional inclusion criteria exist Exclusion Criteria: * Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma * Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months * Current or past history of cardiovascular disease (e.g.. past history of myocardial infarction, ischemic cardiomyopathy) unless cardiology consultation and clearance has been obtained for study participation * History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening * Bulky disease patients - tumors encompassing \>50% of the liver volume and / or inferior vena cava invasion * Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose corticosteroids * Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment * History of severe eczema (as determined by the Investigator) requiring medical treatment * Additional exclusion criteria exist