A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma

Peter Hersey, Jeffrey Sosman, Steven O'Day, Jon Richards, Agop Bedikian, Rene Gonzalez, William Sharfman, Robert Weber, Theodore Logan, Manuela Buzoianu, Luz Hammershaimb, John M. Kirkwood

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

BACKGROUND: The alpha v beta 3vβ3) 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 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. 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.

Original languageEnglish
Pages (from-to)1526-1534
Number of pages9
JournalCancer
Volume116
Issue number6
DOIs
StatePublished - Mar 15 2010

Fingerprint

Integrin beta3
Dacarbazine
Melanoma
Monoclonal Antibodies
etaracizumab
Disease-Free Survival
Integrin alphaVbeta3
Safety
Antibodies, Monoclonal, Humanized
Phase III Clinical Trials
Survival

Keywords

  • Alpha beta
  • Clinical trials
  • Etaracizumab (Abegrin)
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hersey, P., Sosman, J., O'Day, S., Richards, J., Bedikian, A., Gonzalez, R., ... 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(6), 1526-1534. https://doi.org/10.1002/cncr.24821

A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma. / Hersey, Peter; Sosman, Jeffrey; O'Day, Steven; Richards, Jon; Bedikian, Agop; Gonzalez, Rene; Sharfman, William; Weber, Robert; Logan, Theodore; Buzoianu, Manuela; Hammershaimb, Luz; Kirkwood, John M.

In: Cancer, Vol. 116, No. 6, 15.03.2010, p. 1526-1534.

Research output: Contribution to journalArticle

Hersey, P, Sosman, J, O'Day, S, Richards, J, Bedikian, A, Gonzalez, R, Sharfman, W, Weber, R, Logan, T, Buzoianu, M, Hammershaimb, L & Kirkwood, JM 2010, 'A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma', Cancer, vol. 116, no. 6, pp. 1526-1534. https://doi.org/10.1002/cncr.24821
Hersey, Peter ; Sosman, Jeffrey ; O'Day, Steven ; Richards, Jon ; Bedikian, Agop ; Gonzalez, Rene ; Sharfman, William ; Weber, Robert ; Logan, Theodore ; Buzoianu, Manuela ; Hammershaimb, Luz ; Kirkwood, John M. / A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma. In: Cancer. 2010 ; Vol. 116, No. 6. pp. 1526-1534.
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abstract = "BACKGROUND: The alpha v beta 3 (α vβ3) 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 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. 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.",
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AU - Richards, Jon

AU - Bedikian, Agop

AU - Gonzalez, Rene

AU - Sharfman, William

AU - Weber, Robert

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AU - Hammershaimb, Luz

AU - Kirkwood, John M.

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N2 - BACKGROUND: The alpha v beta 3 (α vβ3) 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 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. 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.

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