title: 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.affiliation: MD Anderson Cancer Center, Houston, TX;
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.affiliation: University of California, Los Angeles, CA;
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Pinter-Brown
authors.affiliation: Smilow Cancer Center at Yale New Haven Hospital, New Haven, CT;
authors.forename: Francine M
authors.initials: FM
authors.lastname: Foss
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Lubomir
authors.initials: L
authors.lastname: Sokol
authors.affiliation: MD Anderson Cancer Center, Houston, TX;
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.affiliation: MD Anderson Cancer Center, Houston, TX;
authors.forename: Pramoda
authors.initials: P
authors.lastname: Challagundla
authors.affiliation: Kyowa Hakko Kirin Pharma Inc, Princeton, NJ;
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
authors.affiliation: Kyowa Hakko Kirin Pharma Inc, Princeton, NJ;
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Kyowa Hakko Kirin Pharma Inc, Princeton, NJ;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kurman
authors.affiliation: Kyowa Hakko Kirin Pharma Inc, Princeton, NJ;
authors.forename: Rocco
authors.initials: R
authors.lastname: Ballerini
authors.affiliation: ReSearch Pharmaceutical Services, Inc, Fort Washington, PA; and.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000276:immunology / Q000628:therapy; D011379:Prognosis; D054398:Receptors, CCR4 / Q000276:immunology*; D012751:Sezary Syndrome / Q000276:immunology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C515354:CCR4 protein, human; D054398:Receptors, CCR4; C549035:mogamulizumab