Personalized dosing of immune checkpoint inhibitors by pharmacokinetics/pharmacodynamics analysis and immunogenicity assessment

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07126
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Fukudo Masahide 札幌医科大学, 医学部, 教授 (60437233)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 免疫チェックポイント阻害薬 / 薬物動態 / 薬効 / 抗薬物抗体 / 最適使用法

Outline of Final Research Achievements

We first revealed the incidence of anti-drug antibodies (ADAs) for nivolumab and pembrolizumab as well as ipilimumab in real-world practice. Although ADA titers of the respective drugs examined were relatively low, baseline positive ADA was suggested to relate to systemic symptoms such as fever after start of therapy with nivolumab as well as pembrolizumab. Furthermore, it was suggested that exposure to cemiplimab was associated with clinical activity.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、免疫チェックポイント阻害薬の臨床薬物動態と免疫原性を把握する上で有用な知見を提供するものであり、特に治療薬物モニタリング（therapeutic drug monitoring）を利用した薬物血中濃度測定および抗薬物抗体評価に基づく治療アウトカムの改善が期待され、高額な抗体医薬品の適正使用の推進とそれによる医療費の抑制にも貢献することが考えられる。