抗肿瘤抗体偶联药物临床药理学研究的若干问题与考虑

General considerations for clinical pharmacology of antitumor antibody-conjugated drugs:Implications from FDA review cases

抗体偶联药物(antibody-drug conjugates,ADC)由靶向特异性抗原的抗体药物与有效载荷(如小分子细胞毒药物)通过连接子偶联而成,兼具传统小分子细胞毒药物的强大杀伤效应和抗体药物的肿瘤靶向性。截至2022年2月,美国食品药品监督管理局(FDA)已批准12个ADC抗肿瘤药物。本文通过分析已批准ADC药物的临床药理学审评报告结合相关指导原则,梳理ADC药物临床药理学的研究要点,发现在ADC药物研发中,除临床药理学方面的常规研究外,由于ADC特殊的抗肿瘤作用机制,其剂量选择以及特殊人群用药有着特殊的考虑。希望本文对国内研发人员在开发ADC药物时有所启示。

Antibody-drug conjugates(ADCs)are conjugated by a linker between an antibody drug targeting a specific antigen and a payload,such as a small cytotoxic drug.ADCs combine the potent killing effect of traditional small cytotoxic drugs with the tumor targeting property of antibody drugs.As of February 2022,the U.S.Food and Drug Administration(FDA)had approved 12 ADC anti-tumor agents.Based on the analysis of clinical pharmacology review reports of approved ADC drugs combined with relevant guidelines,it is found that in the development of ADC,in addition to the general research in clinical pharmacology,there are special considerations in dose selection and dose modification for special population due to the special anti-tumor mechanism of ADC.It is hoped that this paper will be enlightening to domestic researchers when developing ADC.