Pharmacodynamic (phase 0) study using etaracizumab in advanced melanoma.

AlphaVbeta3 (alphavbeta3) is an important molecule for tumor-induced angiogenesis and is upregulated in metastatic melanoma (MM). We proposed to study the mechanism of action of etaracizumab, a monoclonal antibody targeting alphavbeta3, in MM. Patients with MM and biopsiable tumor were treated with etaracizumab in 3 dose cohorts starting from 8 mg/kg.

A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin alpha(v)beta(3), + or - dacarbazine in patients with stage IV metastatic melanoma.

Background: The alpha (v) beta (3) (alpha(v)beta(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 alpha(v)beta(3) integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether etaracizumab + or - dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial.

EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell malignancies.

Purpose: We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies.

Experimental Design: We conducted a single-institution phase I dose-escalation trial of siplizumab, a humanized monoclonal antibody to CD2, in 29 patients with T-cell malignancies.

Phase I and pharmacokinetic study of etaracizumab (Abegrin), a humanized monoclonal antibody against alphavbeta3 integrin receptor, in patients with advanced solid tumors.

This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the alphavbeta3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2-5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1-6 mg/kg.

Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis.