Advertisement

A phase I trial of the Fc engineered CD19 antibody XmAb®5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed chronic lymphocytic leukemia

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

Key points

  • XmAb5574 is an Fc engineered CD19 monoclonal antibody which is well tolerated as a single agent in patients with relapsed or refractory CLL.

  • XmAb5574 has preliminary efficacy as a single agent in CLL and is of interest for further study in this disease.

Abstract

CD19 is ubiquitously expressed on CLL cells and is therefore an attractive candidate for antibody targeting. XmAb®5574 (aka MOR00208) is a novel humanized CD19 monoclonal antibody with an engineered Fc region to enhance Fc gamma receptor binding affinity. Here we report results of a first in human Phase I trial of XmAb5574 in patients with relapsed or refractory CLL. 27 patients were enrolled to 6 escalating dose levels, with expansion at the highest dose level of 12 mg/kg. 9 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 exam criteria and laboratory studies, and 8 patients (29.6%) responding by CT criteria. Pharmacokinetics showed a half-life of 14 days with clearance that was not dose-dependent. In conclusion, this Phase I trial demonstrates safety and preliminary efficacy of a novel Fc engineered CD19 monoclonal antibody XmAb5574 and justifies movement into the Phase II setting. Trial is registered on clinicaltrials.gov: NCT01161511.

  • Submitted August 4, 2014.
  • Accepted September 27, 2014.