1. Signed Written Informed Consent: patients must be willing and able to give written
informed consent, that have to be given before starting of screening procedure.
2. Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by
the "Product Specification File".
3. Patients must have histologically or cytologically confirmed malignant unresectable
stage III or stage IV melanoma;
4. Patients must have a minimum of two lesions, one of which must be measurable,(i.e.
that can be accurately measured in two perpendicular dimensions, with at least 1
diameter >20 mm and the other dimension >10 mm with conventional techniques or at
least 10 x 10 mm with spiral CT scan).
5. Patients carrying BRAF mutation-positive melanoma must have received previous
Vemurafenib, unless they are not eligible or refuse the treatment.
6. Patients treated with previous first line therapy must have received Ipilimumab,
unless they are not eligible or refuse the treatment.
7. Pretreated brain metastases which have been clinically stable for at least 6 months
and not requiring corticosteroids are allowed;
8. ECOG performance status 0-1;
9. Negative screening tests for HIV, HBV HCV and syphilis not older than 30 days before
performing any of the GMP-regulated activities required (leukapheresis, collection of
tumor biopsies to be used for tumor lysate/homogenate preparation);
10. Prior lines of chemotherapy, immunotherapy or biological therapy (e.g. inhibitors of
B-Raf or c-Kit, Ipilimumab, etc.) for advanced disease are allowed (patients must have
lasted prior treatments at least 4 weeks before the first vaccine dose);
11. Men and women aged 18-70 years.
12. Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up 8 weeks after the
study, in order to minimize the risk of pregnancy;
13. Patients must have normal organ and marrow function as defined below:
- - leukocytes >1,500/microL
- absolute neutrophil count >1,000/microL
- platelets >80,000/microL
- total bilirubin within 2 x ULN
- AST(SGOT)/ALT(SGPT) <2.5 x ULN
- creatinine ≤ 2 mg/dl
Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing
must be performed within 30 days before any GMP-regulated activity (leukapheresis and
collection of tumor biopsies to be used for tumor lysate/homogenate preparation).
2. Patients with unresectable or metastatic melanoma BRAF V600 mutation-positive eligible
to Vemurafenib cannot be enrolled in first line, unless they refuse this treatment.
3. Patients eligible for Ipilimumab treatment, cannot be enrolled unless they refuse this
4. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier.
5. Participation in another clinical trial with any investigational agents within 30 days
prior to study screening.
6. Patients with known progressing and/or symptomatic brain metastases.
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements (on physician's judgment).
8. Other known malignant neoplastic diseases in the patient's medical history with a
disease-free interval of less than 3 years (except for previously treated basal cell
carcinoma and in situ carcinoma of the uterine cervix);
9. Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g.
severe anemia, piastrinopenia, oral anticoagulant therapy).