NY-ESO-1 Protein Vaccine With Imiquimod in Melanoma (Adjuvant Setting)

This was a Phase 1, single-arm, open-label, pilot study of NY-ESO-1 protein vaccination with imiquimod as an adjuvant in patients with resected Stage IIB, IIC, and III malignant melanoma. The primary study objective was to determine the safety of NY-ESO-1 protein/imiquimod treatment, and the secondary objective was to evaluate the immunogenicity of treatment.

Patients applied imiquimod (250 mg) topically to a designated area of healthy skin on the upper inner arm or inner thigh (the cream remained on the skin overnight for 6-10 hours) every day for 5 consecutive days (i.e., for the first 5 days of Cycles 1-3 and for the first 4 days of Cycle 4). The NY-ESO-1 protein (100 μg) was injected intradermally into the imiquimod-pretreated area on Day 3 of each cycle for 4 consecutive 21-day cycles.

Safety was monitored continuously. Immunization was assessed by the generation of NY-ESO-1-specific cluster of differentiation (CD)4+ and CD8+ T cell responses in enzyme-linked immunosorbent spot (ELISPOT) assays and by the development or augmentation of NY-ESO-1-specific antibody titers, assessed by enzyme-linked immunosorbent assay (ELISA).

Blood samples were obtained for the assessment of clinical biochemistry and hematology, and physical examinations were performed at baseline, on Day 1 of each cycle, and at a follow-up visit at Week 13.

Skin biopsies of the vaccinated area were obtained 48 hours after the last injection (Day 5 of Cycle 4). To avoid irritation, imiquimod was not applied after the biopsies.

Eligibility Criteria:
Inclusion Criteria:

* Had histologically confirmed, resected American Joint Committee on Cancer Stage IIB, IIC or III malignant melanoma
* Fully recovered from surgery
* Age ≥ 18 years; children were excluded from this study, as the safety of imiquimod had not been established in patients below the age of 18
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Adequate organ and marrow function as defined below:

  * absolute neutrophil count: ≥ 1500/μL
  * hemoglobin: ≥ 9 g/dL
  * platelets: ≥ 100,000/μL
  * total bilirubin: ≤ 1.5 × institutional upper limit of normal (ULN)
  * aspartate aminotransferase/alanine aminotransferase (AST/ALT): ≤ 2.5 × institutional ULN
  * creatinine: ≤ 1.5 × institutional ULN
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Received chemotherapy, immunotherapy (including interferon), or radiotherapy within 4 weeks prior to first dosing of study agent
* Prior treatment with NY-ESO-1 vaccines
* Known human immunodeficiency virus infection or autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions could have interfered with the evaluation of the induced immune response; patients with vitiligo or melanoma-associated hypopigmentation were not excluded
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod or other agents used in the study
* 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 have limited compliance with study requirements
* Pregnancy or lactation
* Women of childbearing potential not using a medically acceptable means of contraception
* Known history of inflammatory skin disorders, as imiquimod might have exacerbated these conditions
* Chronic corticosteroid or immunosuppressive therapies, as these might have interfered with the evaluation of the induced immune response
* Lack of availability for immunological and clinical follow-up assessments