Trial of pIL-12 Electroporation Malignant Melanoma

Plasmid IL-12 (pIL-12) at a concentration of 0.5 mg/mL will be injected intratumorally at a
dose volume of ¼ of the calculated lesion volume and a dose volume per lesion of 0.1 mL for
lesions of volume < 0.4 cm3. Six pulses at field strengths of (E+) of 1500 V/cm and pulse
width of 100 μs at 1-second intervals will be administered using the OMS to each previously
injected tumor.

Two treatment regimens will be explored:

Regimen A: Treatment on Days 1, 8 and 15 every 6 weeks Regimen B: Treatment on Days 1, 5 and
8 every 6 weeks. Lesions will be treated on either Regimen A or Regimen B. Subsequent cycles
may be given at 6-week intervals, for up to 9 treatment cycles in total.

Inclusion Criteria:

- Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma

- Age ≥ 18 years of age

- ECOG performance status 0-2

- Patients may have had prior chemotherapy or immunotherapy (vaccines, interferon,
ipilimumab, or IL-2) with progression or persistent disease

- Patients may have had radiation therapy, but must have progressive disease after
radiation therapy if the lesions to be treated are within the radiation field

- Female patient of childbearing potential has a negative pregnancy test within 14 days
prior to the start of study drug

- Adequate organ function

- Able to give informed consent

Exclusion Criteria:

- Prior therapy with IL-12 or prior gene therapy

- Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of subject
participation on study

- Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess,
etc.) at time of study enrollment

- Pregnant or breast-feeding women

- Patients with electronic pacemakers or defibrillators are excluded from this study

- The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has
another confirmed or suspected immunosuppressive or immunodeficient condition
(patients with thyroiditis are eligible)

- Life expectancy of less than 6 months

- History of significant cardiovascular disease (i.e. NYHA class 3 congestive heart
failure; myocardial infarction with the past 6 months; unstable angina; coronary
angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac
arrhythmias)

- Other clinically significant co-morbidities such as uncontrolled pulmonary disease,
uncontrolled diabetes, active CNS disease, active infection or any other condition
that could compromise the patients participation in the study according to the
investigator