The purpose of this study is to determine whether AMG 386, in combination with Sorafenib, is effective in the treatment of advanced or inoperable Hepatocellular cancer in subjects who have not received any prior systemic therapy except surgery or locoregional therapy.

Disease status and disease progression will be assessed every 8 weeks. Subjects will remain on treatment until: progressive disease by RECIST criteria; clinical progression; death or loss to follow-up; or withdrawal of informed consent.

The primary objective is to evaluate the efficacy of AMG 386 in combination with sorafenib as measured by the progression free survival (PFS) rate at 4 months in subjects with advanced or inoperable hepatocellular carcinoma (HCC).

Inclusion Criteria:

• Histologically confirmed advanced or inoperable HCC
• Child-Pugh A liver function score
• Measurable disease with at least one unidimensionally measurable lesion per RECIST 1.0 guidelines with modifications
• Adequate organ and hematological function
• Men or women greater than or equal to 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

Exclusion Criteria:

• Subject is eligible for a liver transplant per investigators discretion
• Any previous systemic chemotherapy for HCC
• History of arterial or venous thromboembolism within 12 months prior to enrollment
• History of clinically significant bleeding within 6 months prior to enrollment
• History of central nervous system metastases
• Clinically significant cardiovascular disease within 12 months
• Uncontrolled hypertension
• Subjects with a history of prior malignancy