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.

© 2015 by The American Society of Hematology.

Figures

Figure 1

Kaplan-Meier curves of estimated progression-free survival. Number of patients at risk are indicated above the x-axis.

Figure 2

Response in blood to mogamulizumab in Sézary syndrome. Patient had received 6 prior systemic therapies. Total CD3+ lymphocytes from peripheral blood are shown. Red, circulating cutaneous T-cell lymphoma cells; green, normal CD3+CD4+ cells; blue, normal CD3+CD4− cells.

Figure 3

Mean plasma mogamulizumab concentration-time profiles for the dose cohorts in phase 1. Bar indicates upper limit of the standard deviation. Purple arrows indicate timing of weekly mogamulizumab administration.