Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma

Leuk Lymphoma. 2015 Jan;56(1):42-8. doi: 10.3109/10428194.2014.911859. Epub 2014 Jul 14.

Abstract

This phase 2 study assessed the safety and efficacy of ocaratuzumab, a humanized anti-CD20 monoclonal antibody. Fifty patients with previously treated follicular lymphoma (FL) and a low-affinity genotype of FcγRIIIa received ocaratuzumab 375 mg/m(2) weekly for 4 weeks. Grade 3/4/5 adverse events (AEs) were reported in 11/1/1 patients, respectively. Serious AEs were reported by 11/50 patients, and three discontinued due to AEs. One patient died from aspiration pneumonia due to possibly drug-related nausea and vomiting. Investigator-assessed response rate was 30% (15/50), including four complete responses (CR), three CR unconfirmed (CRu) and eight partial responses (PR). Investigator-assessed median Progression-free survivial (PFS) was 38.3 weeks. Ocaratuzumab's pharmacokinetic profile was similar to that reported for rituximab. Lymphocyte subset analysis showed significant, selective reduction of B-cells during and after ocaratuzumab treatment. Ocaratuzumab at this dose and schedule is active and well tolerated in patients with previously treated FL with low affinity FcγRIIIa genotypes. ClinTrials registry number: NCT00354926.

Keywords: FcγRIIIa; Follicular lymphoma; ocaratuzumab.

Publication types

  • Case Reports
  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Heterozygote
  • Humans
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / metabolism*
  • Lymphoma, Follicular / mortality
  • Lymphoma, Follicular / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Retreatment
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • FCGR3A protein, human
  • Receptors, IgG
  • ocaratuzumab

Associated data

  • ClinicalTrials.gov/NCT00354926