Novel Adjuvants for Peptide-Based Melanoma Vaccines

In the Phase I/II trial, patients with resected stages III and IV melanoma who have been
rendered free of disease, but are at high risk of relapse, are treated with peptides/IFA at
a dose of 0.5 mg each peptide plus CTLA-4 antibody given intravenously, 3 mg/kg, after each
vaccination. In the Phase II randomized study, patients are treated with the melanoma
peptide vaccine alone, with CTLA-4 antibody, or with CTLA-4 antibody combined with IL-12 at
30 ng/kg with alum. The peptides are tyrosinase 368-376 (370D); gp100 209-217 (210M); and
MART-1 26-35 (27L) which are emulsified with IFA. The dosing schedule for both trials are at
1, 2, 3, 4, 5, and 6 months; then at 9 and 12 for a total of 8 vaccinations.

Inclusion criteria:

- Diagnosis of stage III or IV cutaneous, mucosal, or ocular melanoma

- Completely resected disease or disease-free

- HLA-A2.1 positive

- Tumor tissue available for immunohistochemical analysis and staining positive for at
least 1 of the specified antigens

- At least 1 month since prior therapy for cancer, including radiotherapy and adjuvant
therapy

- WBC count at least 3,000/mm3

- Granulocyte count at least 1,500/mm3

- Platelet count at least 100,000/mm3

- Hemoglobin at least 9.0 gm/dL

- Creatinine no greater than 2.0 mg/dL

- Bilirubin no greater than 2.0 mg/dL

- SGOT/SGPT no greater than 2.5 times upper limit of normal

- ECOG performance status 0-1

- Have failed alpha-interferons (patients with resected stage III disease)

Exclusion criteria:

- Prior treatment with tyrosinase: 368-376(370D), gp100:209-217(210M), and
MART-1:26-35(27L) peptides

- Steroid therapy or other immunosuppressive medication requirement

- Major systemic infections (e.g., pneumonia or sepsis)

- Coagulation or bleeding disorders

- Major medical illnesses of the gastrointestinal, cardiovascular, or respiratory
systems

- Allergic reaction to Montanide ISA 51 (incomplete Freund's adjuvant)

- History of uveitis or autoimmune inflammatory eye disease

- Other active autoimmune disease

- Positive for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody

- Pregnant or nursing