Randomized, Double Blind, Placebo-controlled Topical Resiquimod Adjuvant for NY-ESO-1 Protein Vaccination

There is no published data on the application of topical resiquimod in combination with an
antigen in Montanide, therefore, this study includes a 2-part design where Part I represents
a dose-escalation part with topical resiquimod in an open-label fashion. Part II represents
the randomized part.

In Part I, 2 cohorts are planned: If no dose-limiting toxicity (DLT) occurs by day 8 of the
last vaccination cycle in the last patient enrolled the first cohort, 3 additional patients
(cohort 2) will be enrolled. If no DLT occurs by day 8 of the last vaccination cycle in the
last patient enrolled the second cohort in Part I, the trial will proceed to Part II where
patients will be randomized.

Inclusion Criteria

Patients will be eligible for enrollment if they fulfill the following criteria:

1. Histological diagnosis of surgically resected Stage IIB, IIC, Stage III or Stage IV
(AJCC criteria) melanoma independent of NY-ESO-1 expression in a tumor biopsy

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

3. Laboratory values within the following limits:

Hemoglobin > 10.0 g/dL Neutrophil count > 1.5 x l09/L Lymphocyte count > Lower limit
of institutional normal Platelet count > 80 x l09/L Serum creatinine < 2.0 mg/dL Serum
bilirubin < 2 x upper limit of institutional normal AST/ALT < 2 x upper limit of
institutional normal

4. Patients must have an ECOG performance status of <2 (ECOG criteria published in [46])

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)

8. Patients enrolled in the adjuvant setting must have received standard curative
therapy, e.g., surgery, radiation. Alternatively, patients can enter after refusing
standard curative therapy only if therapy was clearly discussed with the treating
physician or if they have failed another biologic therapy due to toxicity.

Exclusion Criteria

Patients will be excluded from the study if they fulfill any of the following 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 prior to entry into the study.

6. No radiation therapy, prior biological therapy or surgery within 4 weeks prior to
first dose of study agent.

7. No prior chemotherapy or prior vaccine or immunotherapy.

8. Concomitant treatment with systemic corticosteroids greater than physiologic doses.
Topical (but not at the proposed vaccination sites) or inhalational steroids are
permitted. (See also Section 6.7 for restrictions/recommendations on 'Ancillary
Therapy'.)

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. Patients with known history of inflammatory skin disorders (e.g.,psoriasis, lupus)
that may be exacerbated by Resiquimod.

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

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