RATIONALE: Monoclonal antibodies, such as tremelimumab and CD40 agonist monoclonal antibody CP-870,893, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving tremelimumab together with CD 40 agonist monoclonal antibody CP-870, 893 may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of giving tremelimumab together with CD40 agonist monoclonal antibody CP-870,893 in treating patients with metastatic melanoma.
PRIMARY OBJECTIVES: I. To assess the safety, dose-limiting toxicities and maximum tolerated doses of tremelimumab (administered intravenously every 12 weeks) and CP- 870,893 (administered intravenously every 3 weeks). SECONDARY OBJECTIVES: I To seek preliminary evidence of anti-tumor efficacy of the combination of tremelimumab and CP-870,893, including objective response rate at MTD. II. To determine the immune pharmacodynamic changes associated with the administration of the combination of tremelimumab and CP-870,893. OUTLINE: Patients receive tremelimumab IV over 1 hour on day 1 and CD40 agonist monoclonal antibody CP-870,893 IV over 30 minutes on days 2, 22, 43, and 64. Treatment repeats every 12 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States
Toxicity as assessed by CTCAE v3.0
Toxicities which occur during later cycles will be monitored and described separately. The MTD is defined as the dose level at which 0-1/6 patients experience DLT in the first 12 week cycle and at least 2/3 or 2/6 patients treated at the next higher dose level (unless MTD is level 4) experience DLT in the first 12 week cycle.
Time frame: 2 years
Response
Clinical response will be scored using RECIST criteria. Patients who do not complete a clinical response evaluation will be scored as unevaluable. The objective response rate is defined as the proportion of patients treated at the MTD who achieve either a complete or partial response. Unevaluable patients are included in the calculation of the objective response rate.
Time frame: 2 years
Immunological outcomes (analysis of antigen presenting cell activation, antigen-specific T cells, and tumor-specific T cells)
Analysis of antigen presenting cell (APC) activation, 2) analysis of antigen-specific T cells and 3) tumor-specific T cells, as described in Section 7.2. For T cell response analyses, overall immune response is defined as \>2 fold pre-treatment/post-treatment increase in any of the key T cell parameters.
Time frame: 2 years
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