A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL

Jennifer A. Woyach, Farrukh Awan, Ian W. Flinn, Jesus G. Berdeja, Elizabeth Wiley, Sharmeen Mansoor, Ying Huang, Gerard Lozanski, Paul A. Foster, John C. Byrd

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

CD19 is ubiquitously expressed on chronic lymphocytic leukemia (CLL) cells and is therefore an attractive candidate for antibody targeting. XmAb5574 (aka MOR00208) is a novel humanized CD19 monoclonal antibody with an engineered Fc region to enhance Fc g receptor binding affinity. Here we report results of a first in human phase 1 trial of XmAb5574 in patients with relapsed or refractory CLL. Twenty-seven patients were enrolled to 6 escalating dose levels, with expansion at the highest dose level of 12 mg/kg. Nine doses of XmAb5574 were infused over 8 weeks. No maximal tolerated dose was reached, and the drug was generally well tolerated, with infusion reactions of grades 1 and 2 being the most common toxicities. Grade 3 and 4 toxicities occurred in 5 patients and included neutropenia, thrombocytopenia, increased aspartate aminotransferase, febrile neutropenia, and tumor lysis syndrome. XmAb5574 showed preliminary efficacy, with 18 patients (66.7%) responding by physical examination criteria and laboratory studies, and 8 patients (29.6%) responding by computed tomography criteria. Pharmacokinetics showeda half-life of 14 days with clearance that was not dose-dependent. In conclusion, this phase 1 trial demonstrates safety and preliminary efficacy of a novel Fc-engineered CD19 monoclonal antibody XmAb5574 and justifies movement into the phase 2 setting. This trial was registered at www.clinicaltrials.gov as #NCT01161511.

Original languageEnglish (US)
Pages (from-to)3553-3560
Number of pages8
JournalBlood
Volume124
Issue number24
DOIs
StatePublished - Dec 4 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Woyach, J. A., Awan, F., Flinn, I. W., Berdeja, J. G., Wiley, E., Mansoor, S., Huang, Y., Lozanski, G., Foster, P. A., & Byrd, J. C. (2014). A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL. Blood, 124(24), 3553-3560. https://doi.org/10.1182/blood-2014-08-593269