Ticilimumab (CP-675,206) in Treating Patients With Stage IIIC or Stage IV Melanoma

OBJECTIVES: Primary * Determine the change in melanoma intratumoral infiltrates by cluster of differentiation 8 (CD8 positive) cytotoxic T lymphocytes in patients with stage IIIC or IV melanoma treated with ticilimumab (CP-675,206). Secondary * Determine the effects of this drug on intratumoral immune effector cells and tumor cells in these patients. * Determine the effects of this drug on circulating immune effector cells in these patients. * Determine the gene expression profile of immune effector cells and tumor cells in regressing and nonregressing tumors in these patients. * Bank plasma from peripheral blood obtained from patients with regressing and nonregressing tumors for future exploratory analysis of proteomic profile. * Assess additional evidence of antitumor activity of this drug, as measured by best on-study response rate, in these patients. * Characterize the safety profile and tolerability of this drug in these patients. * Obtain pharmacokinetic data to be used in a future meta-analysis of this drug's pharmacokinetics. * Determine whether the CTLA4 genotype influences the safety, immune response, and/or efficacy of this drug in these patients. * Determine the relationships between clinical response (i.e., efficacy or toxicity) and tumor and/or blood ex vivo analysis in patients treated with this drug. OUTLINE: This is an open-label, randomized study. Patients receive ticilimumab (CP-675,206) IV over 2 hours on day 1. Treatment repeats every 90 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection periodically during study for correlative pharmacokinetic (PK), pharmacogenetic, and pharmacogenomic analyses. Blood specimens are obtained for PK measurement at baseline and periodically during study treatment for analysis by enzyme-linked immunosorbent assay. Blood specimens are also evaluated by pharmacogenetic assessment of polymorphisms in CTLA4. Patients also undergo leukapheresis at baseline and at least once between days 30-60 for biomarker analysis of immune cell activation (i.e.,biomarkers CD45RO, CD45RA, HLA-DR, CCR5, CCR7, CD62L, CD69); Treg phenotype (i.e., CD4/CD25/GITR/intracellular FoxP3); and Treg function. In HLA-A2.1 positive patients, peripheral blood mononuclear cells (PBMC) are analyzed for antigen-specific immune reactivity by MART-1, gp100, and tyrosine MHC tetramer using enzyme-linked immunosorbent spot assay. Plasma obtained during leukapheresis is assessed for levels of circulating cytokines and chemokines. Some plasma is stored for future proteomic profile analysis. Patients also undergo excisional or punch biopsy at baseline and between days 30-60 during course 1. Tumor tissue samples embedded in paraffin are analyzed by hematoxylin-eosin and immunohistochemical staining for several biomarkers, including biomarkers of immune cell response (i.e., cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), and cluster of differentiation 8 (CD8) and biomarkers of melanoma (i.e., S-100, MART-1, and/or HMB45). Frozen tumor tissue samples are analyzed by gene chips and gene arrays for gene expression profile and by quantitative real-time polymerase chain reaction for FoxP3. Minced tumor tissue samples are analyzed by flow cytometry in nonadherent cells for HLA-DR (if tumor-infiltrating lymphocytes are available) and by Braf sequencing in adherent cells (if melanoma cells are available). After completion of study therapy, patients are followed every 6 months. PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.