Immunotherapy of HLA-A2 Positive Stage II-IV Melanoma Patients

Vaccination of Melanoma Patients (Stage II-IV) With ImmuFact IMP321, Tumor Antigenic Peptides and Montanide

The purpose of this study is to determine whether vaccination with tumor antigenic peptides and both IMP321/LAG-3 and Montanide adjuvants can induce an immune response in melanoma patients and to assess the safety and tolerability of this vaccination. Tumor responses following this vaccination will also be documented.

The primary objective of this study is:

• to evaluate melanoma antigen specific immune response induced by this vaccination with tumor antigenic peptides derived from MAGE-A3 (Melanoma Antigen family A3) (MHCI: MAGE-A3.A2 and MHCII: MAGE-A3.DP4), NY-ESO-1 (New York Esophageal squamous cell carcinoma antigen-1), Melan A (analog ELA and native EAA) and NA-17A with IMP321 (ImmuFact)/ LAG-3Ig (Lymphocyte activation gene-3 immunoglobulin-like domains) as adjuvant/immunostimulant, formulated with Montanide ISA-51.
• to assess the safety and tolerability of this vaccination

The secondary objective is to document tumor responses in patients following this vaccination.

Inclusion Criteria:

• Histologically confirmed stage II, III or IV melanoma patients.
• Tumor expression of Melan-A.
• Human leukocyte antigen-A2 (HLA-A2) positive.
• Expected survival of at list 3 months.
• Karnofsky scale performance status of 70 % or more.
• Age ≥ 18 years.
• Able to give a written informed consent.
• The following laboratory results:

Hemoglobin ≥ 100g/L, Neutrophil count ≥ 1.5 x 109/L, Lymphocyte count ≥ 0.5 x 109/L, Platelet count ≥ 100 x 109/L, Serum creatinine ≤ 2 mg/dL (0.18mmol/L), Serum bilirubin ≤ 2mg/dL (0.034mmol/L), Granulocyte count > 2.5x109/L, Aspartate Amino Transférase (ASAT), Alanine Amino Transferase (ALAT) < 2.5 x upper limit of normal, Activated Partial Thromboplastin Time (aPTT) within the normal ranges ±25%, Thromplastin (TP) ≥ 80%

Exclusion Criteria:

• Clinically significant heart disease.
• Serious illness, eg. serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders.
• History of immunodeficiency disease or autoimmune disease.
• Metastatic disease to the central nervous system, unless treated and stable.
• Known HIV positivity.
• Known seropositivity for hepatitis B surface antigen.
• Concomitant treatment with steroids, antihistamine drugs. Topical or inhalation steroids are permitted.
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
• Pregnancy or lactation.
• Women of childbearing potential not using a medically acceptable means of contraception.
• Psychiatric or addictive disorders that may compromise the ability to give informed consent.
• Lack of availability of the patient for immunological and clinical follow-up assessment.
• Coagulation or bleeding disorders.
• Kidney dysfunction with creatinine > 2 X the upper limit of the normal value.
• Reported strong (allergic) reactions to previous vaccination.