Investigational New Drugs

, Volume 26, Issue 1, pp 35–43

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

Authors

  • Catherine Delbaldo
    • Department of Medical OncologyBeaujon University Hospital
  • Eric Raymond
    • Department of Medical OncologyBeaujon University Hospital
  • Karina Vera
    • Department of Medical OncologyBeaujon University Hospital
  • Luz Hammershaimb
    • MedImmune Oncology
  • Karen Kaucic
    • MedImmune Oncology
  • Stéphanie Lozahic
    • Department of Medical OncologyBeaujon University Hospital
  • Michel Marty
    • Department of Medical OncologySaint-Louis University Hospital
    • Department of Medical OncologyBeaujon University Hospital
    • Service Inter-Hospitalier de Cancérologie Bichat-BeaujonHôpital Beaujon
Phase I Studies

DOI: 10.1007/s10637-007-9077-0

Cite this article as:
Delbaldo, C., Raymond, E., Vera, K. et al. Invest New Drugs (2008) 26: 35. doi:10.1007/s10637-007-9077-0

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.

Keywords

Angiogenesisαvβ3 receptorAdvanced solid tumorsEndothelial cell adhesionVitaxinMEDI-522

Copyright information

© Springer Science+Business Media, LLC 2007