Ph 1 Trial of ADI-PEG 20 Plus Cisplatin in Patients With Metastatic Melanoma

Inclusion Criteria:

1. Histologically confirmed diagnosis of advanced solid tumor (dose escalation
component) or metastatic melanoma (uveal or cutaneous) (doses escalation and MTD
expansion components) or platinum-resistant (tumor progression within a year after
the completion of platinum-based therapy) ovarian carcinoma (high grade serous,
endometrial or poorly differentiated endometrioid) or HCC that has failed treatment
with sorafenib or did not tolerate sorafenib or refused sorafenib, or HCC with
coexistent BCT that has or has not been treated with chemotherapy, or BCT that has or
has not been treated with chemotherapy. For HCC and HCC with coexistent BCT,
cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should
be determined based on clinical findings and laboratory data during the screening
period (Appendix C). 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.

2. Ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only 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 to be performed retrospectively for the
ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only cohorts. Subjects
with no tissue available would require a biopsy.

3. Unresectable disease or patient refused surgery.

4. Progressive disease if treated with chemotherapy, radiotherapy, surgery or
immunotherapy. If prior radiation was given, the measurable disease should be outside
the radiation port. Unequivocal progression of HCC/BTC lesions previously treated
with catheter-based therapy including transarterial chemoembolization or
radioembolization is allowed.

5. Measurable disease as assessed by RECIST 1.1 criteria (Appendix A).

6. Age ≥ 18 years.

7. ECOG performance status of 0 - 1.

8. No prior systemic therapy, immunotherapy, investigational agent, chemoembolization,
radioembolization or radiation therapy within the last 4 weeks.

9. Fully recovered from any prior surgery and no major surgery within 4 weeks of
initiating treatment, except for gamma knife which can take place within 2 weeks.
Surgery for placement of vascular access devices is acceptable.

Exclusion Criteria:

1. 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. For the HCC, HCC/BTC and
BTC subgroups hepatitis C infection and hepatitis B infection if controlled with
antiviral therapy are allowable.

2. Pregnancy or lactation.

3. Expected non-compliance.

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

5. Subjects who have had any anticancer treatment prior to entering the study and have
not recovered to baseline (except alopecia) or ≤ Grade 1 AEs, or deemed irreversible
from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a
safety risk by the Sponsor and investigator may be allowed upon agreement with both.

6. Subjects with history of another primary cancer, including co-existent second
malignancy, 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 cancer diagnosis.

7. Subjects who had been treated with ADI-PEG 20 previously.

8. History of seizure disorder not related to underlying cancer.

9. Known HIV positivity (testing not required).