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

This is a multi-center, randomized, open-label, Phase 3 study comparing Pexa Vec followed by
sorafenib versus sorafenib in patients with advanced HCC without prior systemic therapy.

A total of 600 patients will be randomly assigned to 2 treatment arms in a 1:1 ratio (300 in
each arm) to reach at least 570 evaluable patients.

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