ny-eso-1 protein vaccine with imiquimod in melanoma (adjuvant setting)

Conditions: Malignant Melanoma

Summary: 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

Keywords: malignant melanoma stages iib-iii