Inclusion Criteria:

1. Male or non-pregnant, non-breast feeding female;

2. Aged between 18 and 75 years;

3. Stage IIIB, stage IIIC or stage IV melanoma with:

- At least 2 cutaneous or subcutaneous non necrotic accessible tumours;

- Tumour size of 1 to 1.5 cm diameter;

- No minimum distance between the 2 selected lesions;

4. Progressive melanoma not responding to previous treatments or patients refusing other
therapies;

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;

6. For women of child-bearing age: effective contraception method (oral contraception or
intra-uterine device) used for more than 2 months before the 1st administration and
to be maintained for 3 months after the last administration of Plasmid AMEP;

7. Having given a written informed consent.

Exclusion Criteria:

1. Patients who can benefit from other melanoma treatments including surgery;

2. Significant cardiac arrhythmias, electronic pacemakers, defibrillators, or any
implanted electronic device;

3. Recent (less than 6 months) acute vascular diseases (stroke, MI…);

4. Advanced peripheral arterial diseases, venous ulcers, or scleroderma;

5. History or treatment of seizures within the last 5 years;

6. Clinically significant abnormality at pre-study full physical examination;

7. Any clinically significant ECG abnormalities;

8. Prior systemic therapy or any other antineoplastic treatments within the last 4
weeks, radiotherapy or surgery unrelated to the fields in question are allowed;

9. Abnormal renal function (creatinine plasma level > ULN);

10. Abnormal liver function tests (any of the following):

- PT < 70%, ASAT, ALAT, alkaline phosphatases, GGT and/or total bilirubin > ULN in
the absence of liver metastasis;

- PT < 70%, ASAT, ALAT > 2 ULN, alkaline phosphatases > 1.5 ULN, GGT > 5 ULN
and/or total bilirubin > 3 ULN in the case of liver metastases;

11. Abnormal bone marrow function: haemoglobin < 10g/dL, WBC < 3.109 /L and/or platelet
count < 100.103 /L;

12. Clinically significant abnormality in pre-study laboratory tests;

13. Evidence of significant active infection (e.g., pneumonia, wound abscess, etc);

14. Intractable coagulopathy;

15. Any significant disease, including psychiatric and dermatology diseases that may
affect the proper evaluation of efficacy or safety;

16. Patients who had participated in another clinical trial in the last 30 days prior to
enrolment in the present clinical trial;

17. Patients unwilling or unable to comply with protocol requirements and scheduled
visits.

Note: patients with brain metastases, or waiting for other therapies (i.e. isolated limb
perfusion) may be included.