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

Hansson, MarkusLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine (author)

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).

Gimsing, Peter (author)
Badros, Ashraf Z (author)
Martinsson Niskanen, Titti (author)
Nahi, HarethKarolinska Institutet (author)
Offner, Fritz (author)
Salomo, Morten (author)
Sonesson, Elisabeth (author)
Mau-Sorensen, Morten (author)
Stenberg, Yvonne (author)
Sundberg, Annika (author)
Teige, IngridLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups(Swepub:lu)infl-ite (author)
van Droogenbroeck, Jan (author)
Wichert, Stina (author)
Zangari, Maurizio (author)
Frendeus, Bjorn (author)
Korsgren, Magnus (author)
Poelman, Martine (author)
Tricot, Guido (author)
Avdelningen för hematologi och transfusionsmedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

In:Clinical Cancer Research21:12, s. 2730-27361078-0432
In:Clinical cancer research : an official journal of the American Association for Cancer Research21:12, s. 2730-27361557-3265

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.