A Phase I Dose-Ranging Safety Study Using Intranodal Delivery of a Plasmid DNA (Synchrotope TA2M) in Adult Stage IV Melanoma Patients

Inclusion Criteria

INCLUSION CRITERIA - Patient must meet the following during the screening and baseline
visits:

1. The patients or their legally acceptable representative must give signed informed
consent for participation in the study before any study procedure is performed.

2. Patients must be 18 years of age or older at pre-study

3. Patients must be ambulatory, ECOG performance status of 0 or 1 (Appendix II)

4. Patients have histologically confirmed diagnosis of Stage IV melanoma according to
AJCC/UICC modified system with an expected survival time of more than 3 months

5. Patients must be positive for HLA-A2 (Patients tested positive within 5 years of
pre-study screening do not need to be tested again for HLA-A2)

6. Patients must agree to use an acceptable method of birth control

1. intrauterine device

2. oral hormonal contraception

3. combination of spermicide and barrier method or

4. abstinence

7. Female patients of childbearing potential must have a confirmed negative urine
pregnancy test on Day 0

EXCLUSION CRITERIA - Patients meeting any of the following criteria will NOT be eligible
for the study:

1. Patients who have hematological abnormalities as evidenced by:

1. Neutrophils < 1,500/mm3

2. Leukocytes < 3,000/mm3

3. Platelets < 75,000/mm3

4. Hemoglobin < 9.0 g/dL

2. Patients who have hepatic disease as evidenced by:

1. SGOT/SGPT (AST/ALT) > 2.5 x the upper limit of normal (ULN)

2. alkaline phosphatase > 2.5 x ULN

3. Bilirubin > 1.5 x ULN\

4. positive for hepatitis B surface antigen

5. positive for hepatitis C antibody

3. Patients who have known or suspected renal impairment as evidenced by:

1. serum creatinine > 1.5 x ULN, and/or

2. serum urea > 2.6 x ULN

4. Patients with a history of ocular melanoma

5. Patients with brain metastases, unless completed resected

6. Patients with a positive HIV antibody test

7. Patients with medical, sociological, or psychological impediments that may compromise
compliance with the protocol

8. Patients who are nursing, pregnant or planning to become pregnant within 6 months of
treatment completion

9. Patients who are receiving chemo-, radio- or immunotherapy concurrently or within the
preceding four weeks

10. Patients who are taking drugs that affect immune function such as systemic
corticosteroids or immunomodulatory drugs concurrently or within the preceding four
weeks

11. Patients who are receiving any investigational drug concurrently or within the
preceding four weeks