A Randomized, Double-Blind, Multi-Center Phase 3 Study of ADI-PEG 20 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Subjects With Advanced Hepatocellular Carcinoma (HCC) Who Have Failed Prior Systemic Therapy

Inclusion Criteria:

- Prior diagnosis of HCC confirmed histologically.

- Prior treatment with at least 1 systemic agent, with documented progressive disease
after systemic agent(s), or adverse event(s)associated with prior systemic agent(s)
that resulted in discontinuance of that agent(s).

- Cirrhotic status of Child-Pugh grade B7.

- Expected survival of at least 3 months.

- Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

- Candidate for potential curative therapies (i.e., resection or transplantation) or
loco-regional approaches (i.e., ablation, embolization).

- Significant cardiac disease.

- Serious infection requiring treatment with systemically administered antibiotics.

- Pregnancy or lactation.

- Expected non-compliance.

- Uncontrolled intercurrent illness, or psychiatric illness or social situations that
would limit compliance with study requirements.

- Subjects who have had any anticancer treatment within 2 weeks prior to entering the
study.

- Subjects who have not fully recovered from toxicities associated with previous HCC
loco-regional or systemic therapies.

- Subjects with history of another primary cancer, with the exception of: a) curatively
resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;
or c) other primary solid tumor with no known active disease present in the opinion
of the investigator will not affect patient outcome in the setting of current HCC
diagnosis.

- Allergy to pegylated products.

- Bleeding esophageal or gastric varices within the prior three months, except if
banded or treated.

- Subjects known to be HIV positive.

- Uncontrolled ascites (defined as not easily controlled with diuretic treatment).

- Having received any blood transfusion, blood component preparation, erythropoietin,
albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days
prior to screening laboratories or after screening laboratories have been obtained
until first dose of study drug or placebo.

- Use of traditional medicines approved by local authorities, including but not limited
to Chinese herbs within 14 days of first dose of study drug or placebo.

- ECOG performance status > 2.

- Prior allograft,including liver transplant.