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

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.

• Authors: Madeleine Duvic, Lauren C Pinter-Brown, Francine M Foss, Lubomir Sokol, Jeffrey L Jorgensen, Pramoda Challagundla, Karen M Dwyer, Xiaoping Zhang, Michael R Kurman, Rocco Ballerini, Li Liu, Youn H Kim
• Journal: Blood (Blood) Vol. 125 Issue 12 Pg. 1883-9 (Mar 19 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25605368 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

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

Topics

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