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A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma†
Article first published online: 27 JAN 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 6, pages 1526–1534, 15 March 2010
How to Cite
Hersey, P., Sosman, J., O'Day, S., Richards, J., Bedikian, A., Gonzalez, R., Sharfman, W., Weber, R., Logan, T., Buzoianu, M., Hammershaimb, L. and Kirkwood, J. M. (2010), A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma. Cancer, 116: 1526–1534. doi: 10.1002/cncr.24821
The authors thank Miriam Gitler, PhD, MedImmune, LLC, for her assistance in preparation of the manuscript.
- Issue published online: 3 MAR 2010
- Article first published online: 27 JAN 2010
- Manuscript Accepted: 10 JUN 2009
- Manuscript Revised: 9 JUN 2009
- Manuscript Received: 8 APR 2009
- etaracizumab (Abegrin);
- alpha v beta 3;
- clinical trials
The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis.
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 αvβ3 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.
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.
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.