[Development of mogamulizumab and establishment of an optimal therapy based on genomic biomarkers: from the academic viewpoint].

Mogamulizumab (Moga; KW-0761) is a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody engineered to exert potent antibody-dependent cellular cytotoxicity (ADCC). A collaborative investigation with industry in preclinical studies has demonstrated in vitro and in vivo efficacy via ADCC for adult T-cell leukemia/lymphoma (ATLL) and CCR4-positive peripheral T-cell lymphoma (PTCL). In a phase I study, once-weekly administration of mogamulizumab (0.01-1.0 mg/kg) for 4 weeks was well tolerated. In a phase II study of once-weekly mogamulizumab (1.0 mg/kg) for 8 weeks in relapsed/refractory ATLL patients, an overall response rate of 50% including 30% complete response rate with a median progression-free survival of 5.2 months was observed. The drug was subsequently approved by Pharmaceuticals and Medical Devices Agency(PMDA) in March 2012. Because CCR4 is abundantly expressed on the surface of effector regulatory T cells, a phase I study is being conducted to enhance antitumor immune response in patients with solid tumors. However, approximately 60% of patients receiving mogamulizumab experience skin eruption with 19% showing grade ≥ 3 rash. Postmarketing surveillance of mogamulizumab revealed a 3-4% incidence rate of skin-related serious adverse events (SAEs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Therefore we initiated a search for predictive genomic biomarkers in the blood of patients with ATLL or solid tumors prior to treatment with mogamulizumab for not only efficacy but also immune-related SAEs. We believe the results of this study may lead to safer and more efficient use of this agent in the near future.