Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma

Blood. 2015 Mar 19;125(12):1883-9. doi: 10.1182/blood-2014-09-600924. Epub 2015 Jan 20.

Abstract

This phase 1/2 study evaluated the efficacy of mogamulizumab, a defucosylated, humanized, anti-CC chemokine receptor 4 monoclonal antibody, in 41 pretreated patients with cutaneous T-cell lymphoma. No dose-limiting toxicity was observed and the maximum tolerated dose was not reached in phase 1 after IV infusion of mogamulizumab (0.1, 0.3, and 1.0 mg/kg) once weekly for 4 weeks followed by a 2-week observation. In phase 2, patients were dosed with 1.0 mg/kg mogamulizumab according to the same schedule for the first course followed by infusion every 2 weeks during subsequent courses until disease progression. The most frequent treatment-emergent adverse events were nausea (31.0%), chills (23.8%), headache (21.4%), and infusion-related reaction (21.4%); the majority of events were grade 1/2. There were no significant hematologic effects. Among 38 evaluable patients, the overall response rate was 36.8%: 47.1% in Sézary syndrome (n = 17) and 28.6% in mycosis fungoides (n = 21). Eighteen of 19 (94.7%) patients with ≥B1 blood involvement had a response in blood, including 11 complete responses. Given the safety and efficacy of mogamulizumab, phase 3 investigation of mogamulizumab is warranted in cutaneous T-cell lymphoma patients. This trial was registered at www.clinicaltrials.gov as #NCT00888927.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Lymphoma, T-Cell, Cutaneous / immunology*
  • Lymphoma, T-Cell, Cutaneous / therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Mycosis Fungoides / immunology
  • Mycosis Fungoides / therapy
  • Prognosis
  • Receptors, CCR4 / immunology*
  • Sezary Syndrome / immunology
  • Sezary Syndrome / therapy
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • CCR4 protein, human
  • Receptors, CCR4
  • mogamulizumab

Associated data

  • ClinicalTrials.gov/NCT00888927