Study of Mapatumumab in Combination With Sorafenib in Subjects With Advanced Hepatocellular Carcinoma

Inclusion Criteria:

- Child-Pugh Class A.

- Barcelona Clinic Liver Cancer (BCLC) advanced stage (C) hepatocellular carcinoma, or
BCLC intermediate stage (B) hepatocellular carcinoma if treatment with transarterial
chemoembolization is not considered appropriate

- Measurable disease demonstrating intratumoral arterial enhancement by contrast
enhanced computerized tomography (CT), with use of multislice scanners, or contrast
enhanced dynamic magnetic resonance imaging (MRI), with at least 1 tumor lesion that
meets the following criteria: located in the liver; can be accurately measured in at
least 1 dimension; well delineated area of viable, hypervascular (contrast enhancement
in the arterial phase) tumor that is >2 centimeter (cm) in the axial plane; suitable
for repeat measurement; OR not previously treated with locoregional or systemic
treatment unless the lesion shows a well-delineated area of viable (contrast
enhancement in the arterial phase) tumor that is >2 cm in the axial plane. (If the
lesion is poorly demarcated or exhibits atypical enhancement as a result of the
previous intervention, then it cannot be selected as a target lesion)

- Radiologic eligibility (measurable disease) must be must be confirmed by the BICR
prior to randomization.

- Adequate bone marrow, renal and liver function as defined in the protocol.

- Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale

- Age 18 years or older

- Have the ability to understand the requirements of the study, provide written informed
consent (including consent for the use and disclosure of research-related health
information), and comply with the study and follow-up procedures.

Exclusion Criteria:

- Any co-morbid condition that in the judgment of the investigator renders the subject
at high risk of treatment complications or reduces the possibility of assessing
clinical effect.

- Received prior investigational or non-investigational cytotoxic chemotherapy, hormonal
therapy, biological therapy (including but not limited to monoclonal antibodies, small
molecules or other immunotherapy) to treat hepatocellular carcinoma.

- History of organ allograft.

- Previously received mapatumumab or sorafenib.

- Underwent resection, radiofrequency ablation, radiation or chemoembolization within 4
weeks before enrollment or not recovered from such treatments.

- Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy,
immunotherapy, radiofrequency ablation) or other investigational agents during the
study treatment period.

- Major surgery (i.e., the opening of a major body cavity, requiring the use of general
anesthesia) within 4 weeks before enrollment; minor surgery (except for insertion of
vascular access device) within 2 weeks before enrollment; or not yet recovered from
the effects of the surgery.

- Systemic steroids within 1 week before enrollment except steroids used as part of an
antiemetic regimen or maintenance-dose steroids for non-cancerous disease.

- Hepatic encephalopathy, per the investigator's evaluation.

- History of clinically significant gastrointestinal bleeding requiring procedural
intervention (e.g., variceal banding, transjugular intrahepatic portosystemic shunt
procedure, arterial embolization, topical coagulation therapy) within 4 weeks before
enrollment.

- Gastrointestinal disease resulting in an inability to take oral medication or a
requirement for intravenous hyperalimentation.

- History of any infection requiring hospitalization or intravenous antibiotics within 2
weeks before enrollment.

- Known brain or spinal cord metastases unless adequately treated (surgery or
radiotherapy) with no evidence of progression and neurologically stable off
anticonvulsants and steroids.

- Known human immunodeficiency virus infection.

- Unstable angina, myocardial infarction, cerebrovascular accident, >= Class II
congestive heart failure according to the New York Heart Association Classification
for Congestive Heart Failure within 6 months before enrollment.

- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
digoxin.

- Uncontrolled hypertension (systolic blood pressure >150 millimeters of mercury [mmHg]
or diastolic pressure >90 mmHg despite optimal medical management).

- Using and unable to discontinue use of concomitant strong CYP3A4 inducers (e.g.,
including but not limited to St. John's Wort, dexamethasone, phenytoin, carbamazepine,
rifampin, rifabutin, phenobarbital)

- Pregnant female or nursing mother. All females with an intact uterus (unless
amenorrheic for the 24 months before enrollment) must have a negative serum pregnancy
test at screening. All non-sterile or non-postmenopausal females must practice a
medically accepted method of contraception over the course of the study and for 60
days after the last dose of study agent.

- Males who do not agree to use effective contraception during the study and for a
period of 60 days following the final dose of study agent.

- Subject is currently enrolled in or has not yet completed at least 30 days since
ending other investigational device or drug study(s) or subject is receiving other
investigational agents.

- Acute or chronic severe renal insufficiency (glomoerular filtration rate <30
milliliters [mL]/minute/1.73 square meters) or acute renal insufficiency of any
severity due to the hepato-renal syndrome.

- Hepatitis B virus deoxyribonucleic acid (DNA) levels >2,000 international units/mL.