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Phase I and pharmacokinetic study of etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors

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Summary

This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the αvβ3 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. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of etaracizumab warrants further exploration in ongoing phase I/II trials.

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Acknowledgments

Dr. Delbaldo was supported by a grant from the “Ligue Genevoise contre le Cancer”.

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Authors and Affiliations

  1. Department of Medical Oncology, Beaujon University Hospital, Clichy, France

    Catherine Delbaldo, Eric Raymond, Karina Vera, Stéphanie Lozahic & Sandrine Faivre

  2. Department of Medical Oncology, Saint-Louis University Hospital, Paris, France

    Michel Marty

  3. MedImmune Oncology, One MedImmune Way, Gaithersburg, MD, 20878, USA

    Luz Hammershaimb & Karen Kaucic

  4. Service Inter-Hospitalier de Cancérologie Bichat-Beaujon, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92118, Clichy Cedex, France

    Sandrine Faivre

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  1. Catherine Delbaldo
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Correspondence to Sandrine Faivre.

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Delbaldo, C., Raymond, E., Vera, K. et al. Phase I and pharmacokinetic study of etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors. Invest New Drugs 26, 35–43 (2008). https://doi.org/10.1007/s10637-007-9077-0

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  • DOI: https://doi.org/10.1007/s10637-007-9077-0

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