A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin α v β 3 , ± dacarbazine in patients with stage IV metastatic melanoma

BACKGROUND: The alpha v beta 3 (α v β 3 ) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor‐induced angiogenesis. METHODS: This phase 2, randomized, open‐label, 2‐arm study was designed to capture safety data and evaluate the antitumor efficacy of etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the α v β 3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive etaracizumab alone (N = 57) or etaracizumab + dacarbazine (N = 55). Safety of etaracizumab ± dacarbazine was acceptable with infusion‐related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the etaracizumab‐alone study arm and 12.7% of patients in the etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression‐free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the etaracizumab‐alone study arm and 40.0% of patients in the etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the etaracizumab‐alone study arm and 2.5 and 2.6 months in the etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the etaracizumab‐alone study arm and 9.4 months in the etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.