Phase II Randomized, Open-Label Study of IMC-1121B With or Without Dacarbazine in Patients with Metastatic Malignant Melanoma

INTERVENTION: Product Name: IMC‐1121B Product Code: IMC‐1121B Pharmaceutical Form: Solution for infusion CAS Number: 947 687‐13‐0 Current Sponsor code: IMC‐1121B Other descriptive name: recombinant human IgG1 monoclonal antibody (MAb) targeted to VEGFR‐2 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 5‐ Product Name: Dacarbazine Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: Dacarbazine CAS Number: 4342‐03‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Product Name: Dacarbazine Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: Dacarbazine CAS Number: 4342‐03‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ CONDITION: Metastatic Malignant Melanoma ; MedDRA version: 9.1 Level: LLT Classification code 10027480 Term: Metastatic malignant melanoma PRIMARY OUTCOME: Main Objective: The primary objective is to determine the progression‐free survival (PFS) of patients with metastatic malignant melanoma who have not received prior chemotherapy for metastatic disease when treated with IMC‐1121B alone or in combination with dacarbazine. Primary end point(s): The primary efficacy endpoint for this study is PFS. PFS is defined as the time from the day of randomization to the first evidence of progression as defined by RECIST or death from any cause. Patients who die without a reported prior progression will be considered to have progressed on the day of their death. Patients who do not progress and are subsequently lost to follow‐up will have their data censored at the day of their last tumor assessment.; The Kaplan‐Meier method will be used to analyze PFS and to estimate the median survival time. The Kaplan‐Meier survival curves will be presented as stratified. Log‐rank test will be used to compare the survival curves for the stratification factors LDH status and extent‐of‐metastasis. The 95% confidence interval for the median survival time will be provided. A univariate Cox proportional hazards model analysis will be performed using treatment as a simple covariate and LDH status and extent of metastasis as strata. Secondary Objective: The secondary objectives will be to:; • Assess the safety and tolerability of IMC‐1121B alone and in combination with dacarbazine; • Measure overall response rate (ORR); • Determine median duration of response; • Measure stable disease rate at 6 weeks and 12 weeks; • Determine 12‐week response rate; • Assess the pharmacokinetics of IMC‐1121B alone and in combination with dacarbazine; INCLUSION CRITERIA: 1. The patient has histologically or cytologically confirmed cutaneous malignant melanoma that is American Joint Committee on Cancer (AJCC) stage IV (metastatic). 2. The patient is = 18 years of age. 3. The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0‐1. 4. The patient has completed any prior radiotherapy, biologic/immunotherapy or vaccine therapy (for adjuvant or advanced disease) at least 6 weeks prior to the first dose of study therapy. 5. The patient has a life expectancy > 3 months. 6. The patient has evidence of measurable disease as defined by RECIST. 7. The patient has resolution of all clinically significant toxic effects of prior cancer therapy to grade = 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI‐CTCAE). 8. The patient has adequate hematological functions (absolute neutrophil count [ANC] = 1500 cells/µL, hemoglobin = 9 g/dL and platelet