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A phase 1 dose-escalation study of antibody BI-505 in relapsed/refractory multiple myeloma.

Hansson, Markus LU ; Gimsing, Peter; Badros, Ashraf Z; Martinsson Niskanen, Titti; Nahi, Hareth; Offner, Fritz; Salomo, Morten; Sonesson, Elisabeth; Mau-Sorensen, Morten and Stenberg, Yvonne, et al. (2015) In Clinical Cancer Research 21(12). p.2730-2736
Abstract
Purpose: 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. Experimental design: BI-505 was given intravenously, every two 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... (More)
Purpose: 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. Experimental design: BI-505 was given intravenously, every two 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, seven patients on extended therapy had stable disease for more than two months. Conclusion: 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). (Less)
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published
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Clinical Cancer Research
volume
21
issue
12
pages
2730 - 2736
publisher
American Association for Cancer Research
external identifiers
  • pmid:25712687
  • wos:000357336600012
  • scopus:84941955989
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-14-3090
language
English
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yes
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fcd48262-d969-424f-b10d-65e12cc5d0a7 (old id 5142864)
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http://www.ncbi.nlm.nih.gov/pubmed/25712687?dopt=Abstract
date added to LUP
2015-03-10 21:43:30
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2017-10-22 03:07:25
@article{fcd48262-d969-424f-b10d-65e12cc5d0a7,
  abstract     = {Purpose: 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. Experimental design: BI-505 was given intravenously, every two 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, seven patients on extended therapy had stable disease for more than two months. Conclusion: 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).},
  author       = {Hansson, Markus and Gimsing, Peter and Badros, Ashraf Z and Martinsson Niskanen, Titti and Nahi, Hareth and Offner, Fritz and Salomo, Morten and Sonesson, Elisabeth and Mau-Sorensen, Morten and Stenberg, Yvonne and Sundberg, Annika and Teige, Ingrid and van Droogenbroeck, Jan and Wichert, Stina and Zangari, Maurizio and Frendeus, Bjorn and Korsgren, Magnus and Poelman, Martine and Tricot, Guido},
  issn         = {1078-0432},
  language     = {eng},
  number       = {12},
  pages        = {2730--2736},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {A phase 1 dose-escalation study of antibody BI-505 in relapsed/refractory multiple myeloma.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-14-3090},
  volume       = {21},
  year         = {2015},
}