Ph 1 Trial of ADI PEG 20 Plus Sorafenib to Treat Patients With Liver Cancer

Inclusion Criteria:

1. Prior diagnosis of HCC confirmed histologically.

2. HCC tissue either from an archived specimen or from a new biopsy of sufficient amount
and quality should be available for IHC determination of ASS status, and other
biomarkers, to be performed retrospectively. Subjects with no tissue available would
require a biopsy.

3. No prior treatment with systemic chemotherapy (except as noted in exclusion criteria
# 10).

4. Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable
lesion must be present. Subjects who have received local-regional therapy such as
(but not limited to) chemoembolization, embolization, cryoablation, hepatic artery
therapy, percutaneous ethanol injection, radiation therapy, radiofrequency ablation
or surgery are eligible, provided that they have either a target lesion which has not
been treated with local therapy and/or the target lesion(s) within the field of the
local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy
must be completed at least 4 weeks prior to the baseline CT scan. Local therapies
including chemoembolization do not count as prior systemic therapy.

5. Cirrhotic status of Child-Pugh grade A. Child-Pugh status should be determined based
on clinical findings and laboratory data during the screening period (Appendix B).
Subjects on anti-coagulants are to receive 1 point for their INR status, as they are
presumed to have a <1.7 baseline PT/INR.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix C).

7. Expected survival of at least 3 months.

8. Age ≥ 18 years.

Exclusion Criteria:

1. Candidate for potential curative therapies (i.e., resection or transplantation).

2. Prior allograft transplantation including liver transplantation.

3. Serious infection requiring treatment with systemically administered antibiotics at
the time of study entrance, or an infection requiring systemic antibiotic therapy
within 7 days prior to the first dose of study treatment.

4. Pregnancy or lactation.

5. Expected non-compliance.

6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (New York Heart Association Class III
or IV; Appendix D), unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness or social situations that would limit compliance with study requirements.

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

8. 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.