title: A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma.
abstract: OBJECTIVE
  This multicenter, first-in-human study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-505, a human anti-ICAM-1 monoclonal antibody, in advanced relapsed/refractory multiple myeloma patients.
  
  
  METHODS
  BI-505 was given intravenously, every 2 weeks, at escalating doses from 0.0004 to 20 mg/kg, with extension of therapy until disease progression for responding or stable patients receiving 0.09 mg/kg or higher doses.
  
  
  RESULTS
  A total of 35 patients were enrolled. The most common adverse events were fatigue, pyrexia, headache, and nausea. Adverse events were generally mild to moderate, and those attributed to study medication were mostly limited to the first dose and manageable with premedication and slower infusion. No maximum tolerated dose was identified. BI-505's half-life increased with dose while clearance decreased, suggesting target-mediated clearance. The ICAM-1 epitopes on patient bone marrow myeloma were completely saturated at 10 mg/kg doses. Using the International Myeloma Working Group criteria, 7 patients on extended therapy had stable disease for more than 2 months.
  
  
  CONCLUSIONS
  BI-505 can be safely administered at doses that saturate myeloma cell ICAM-1 receptors in patients. This study was registered at www.clinicaltrials.gov (NCT01025206).
authors.affiliation: Department of Hematology, Skåne University Hospital and Lund University, Lund, Sweden. markus.hansson@med.lu.se.
authors.forename: Markus
authors.initials: M
authors.lastname: Hansson
authors.affiliation: Department of Hematology, Copenhagen University and Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Gimsing
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Titti Martinsson
authors.initials: TM
authors.lastname: Niskanen
authors.affiliation: Department of Medicine, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
authors.affiliation: Department of Hematology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
authors.affiliation: Department of Hematology, Copenhagen University and Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Salomo
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sonesson
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Mau-Sorensen
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Stenberg
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Sundberg
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Teige
authors.affiliation: Department of Hematology, AZ St Jan Hospital, Bruges, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Droogenbroeck
authors.affiliation: Department of Hematology, Skåne University Hospital and Lund University, Lund, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Wichert
authors.affiliation: Myeloma Institute, University of Arkansas, Little Rock, Arkansas.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Frendeus
authors.affiliation: Clinical Development, BioInvent International AB, Lund, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Korsgren
authors.affiliation: Medical and Scientific Department, Covance Inc., Brussels, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Poelman
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents