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[Development of mogamulizumab and establishment of an optimal therapy based on genomic biomarkers: from the academic viewpoint].
Yakugaku Zasshi 2015; 135(5):663-9YZ

Abstract

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.

Authors+Show Affiliations

Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

jpn

PubMed ID

25948299

Citation

Iida, Shinsuke, et al. "[Development of Mogamulizumab and Establishment of an Optimal Therapy Based On Genomic Biomarkers: From the Academic Viewpoint]." Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, vol. 135, no. 5, 2015, pp. 663-9.
Iida S, Ishida T, Ueda R. [Development of mogamulizumab and establishment of an optimal therapy based on genomic biomarkers: from the academic viewpoint]. Yakugaku Zasshi. 2015;135(5):663-9.
Iida, S., Ishida, T., & Ueda, R. (2015). [Development of mogamulizumab and establishment of an optimal therapy based on genomic biomarkers: from the academic viewpoint]. Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, 135(5), pp. 663-9. doi:10.1248/yakushi.14-00230-3.
Iida S, Ishida T, Ueda R. [Development of Mogamulizumab and Establishment of an Optimal Therapy Based On Genomic Biomarkers: From the Academic Viewpoint]. Yakugaku Zasshi. 2015;135(5):663-9. PubMed PMID: 25948299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Development of mogamulizumab and establishment of an optimal therapy based on genomic biomarkers: from the academic viewpoint]. AU - Iida,Shinsuke, AU - Ishida,Takashi, AU - Ueda,Ryuzo, PY - 2015/5/8/entrez PY - 2015/5/8/pubmed PY - 2016/9/13/medline SP - 663 EP - 9 JF - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan JO - Yakugaku Zasshi VL - 135 IS - 5 N2 - 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. SN - 1347-5231 UR - https://www.unboundmedicine.com/medline/citation/25948299/[Development_of_mogamulizumab_and_establishment_of_an_optimal_therapy_based_on_genomic_biomarkers:_from_the_academic_viewpoint]_ L2 - https://dx.doi.org/10.1248/yakushi.14-00230-3 DB - PRIME DP - Unbound Medicine ER -