Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

This is a Phase I open label dose escalation study of the TLR3 agonist Poly-ICLC as an
adjuvant for NY-ESO-1 protein vaccination in patients with high risk melanoma in clinical
complete remission (cCr), followed by a randomized Phase II component in which patients will
be randomized to subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD
(Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide® ISA-51 VG (Montanide)
(Arm B).

Patients with histological confirmed malignant melanoma, AJCC Stages: IIB, IIC, III or IV,
who are in complete clinical remission (cCr) but at high risk of disease recurrence, will be
eligible for enrollment, regardless of whether antigen expression in the autologous tumor can
be demonstrated by either PCR or immunohistochemistry.

Primary Objectives:

- Phase I: To define the safety of subcutaneous vaccination with NY-ESO-1 protein,
Montanide and escalating doses of Poly-ICLC.

- Phase II: To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to
subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given
with or without Montanide.

Exploratory analyses:

- Evaluation of primary tumor expression of NY-ESO-1 by IHC or RT-PCR.

- Histologic quantitation of original tumor TILs (tumor infiltrating lymphocytes), CD3+
cells, evaluation of mitotic index and correlation of this data with immunologic
response.

- Correlation of NY-ESO-1 specific T cell responses with HLA type

- Investigation of polymorphisms for TLR3 through germline SNP analysis.

- Clinical Outcome (Time to Progression) reported descriptively.

- Skin section analysis of protein/adjuvant treated sites for immune cell infiltration and
gene expression analysis

Inclusion Criteria

1. Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically
confirmed cCr without clinical evidence of disease.

2. At least 4 weeks since surgery prior to first dosing of study agent.

3. Laboratory values within the following limits:

1. Hemoglobin > 10.0 g/dL

2. Neutrophil count > 1.5 x l09/L

3. Lymphocyte count > Lower limit of institutional normal

4. Platelet count > 80 x l09/L

5. Serum creatinine < 2.0 mg/dL

6. Serum bilirubin < 2 x upper limit of institutional normal

7. AST/ALT < 2 x upper limit of institutional normal

4. Patients must have an ECOG performance status of <2 (ECOG criteria published in [67].

5. Life expectancy > 6 months.

6. Age > 18 years.

7. Able and willing to give written informed consent for participation in the trial (see
Section 12.2).

Exclusion Criteria

1. Serious illnesses, e.g., serious infections requiring antibiotics.

2. Previous bone marrow or stem cell transplant.

3. History of immunodeficiency disease (such as HIV) or autoimmune disease except
vitiligo.

4. Metastatic disease to the central nervous system.

5. Other malignancy within 3 years prior to entry into the study, except for treated
early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.

6. Prior chemotherapy or vaccine therapy.

7. Radiation therapy, biological therapy or surgery within 4 weeks prior to first dose of
study agent.

8. Concomitant treatment with systemic corticosteroids greater than physiologic doses.
Topical (but not at the proposed vaccination sites) or inhalational steroids are
permitted.

9. Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to first dose of study agent.

10. Pregnancy or lactation.

11. Women of childbearing potential not using a medically acceptable means of
contraception.

12. Psychiatric or addictive disorders that may compromise the ability to give informed
consent.

13. Lack of availability of the patient for immunological and clinical follow-up
assessment.

14. Children <18 years of age who cannot undergo the leukapheresis procedure, do not meet
the disease staging and/or the size criteria for frequent blood donations