Immune checkpoint inhibitors are monoclonal antibodies (mAbs) directed against negative immunologic regulators that are used to restore the immune response against cancer. Approved drugs include anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death-ligand 1 (PD-L1) antibodies exhibiting pharmacokinetic (PK) characteristics typical of mAbs. Most factors such as age, sex, ethnicity, tumour burden, performance status and immunogenicity, but not body weight, do not seem to affect drug clearance clinically. However, an exposure-response relation has been described for both the efficacy and toxicity of anti-CTLA-4 and anti-PD-1 agents. The change in clearance over time is associated with overall response at least for nivolumab and pembrolizumab. Few PK/pharmacodynamic (PD) data are available for anti-PD-L1 mAbs, but time-varying clearance has been described for these drugs, and the high immunogenicity rate observed with atezolizumab may affect PK parameters and should be further studied. These data suggest the need for additional PK/PD studies. In this review, we summarise studies of the PKs of immune checkpoint inhibitors, exploring possible interactions with PD considerations.

中文翻译：

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肿瘤学中使用的治疗性单克隆抗体的药代动力学/药效关系：第2部分，免疫检查点抑制剂抗体。

免疫检查点抑制剂是针对阴性免疫调节剂的单克隆抗体（mAb），可用于恢复针对癌症的免疫反应。批准的药物包括具有典型药代动力学（PK）特征的抗细胞毒性T淋巴细胞抗原4（CTLA-4），抗程序性细胞死亡1（PD-1）和抗程序性细胞死亡配体1（PD-L1）抗体单克隆抗体。大多数因素，例如年龄，性别，种族，肿瘤负担，工作状态和免疫原性，但不影响体重，似乎并不影响临床上的药物清除率。然而，已经描述了抗CTLA-4和抗PD-1剂的功效和毒性的暴露-反应关系。清除率随时间的变化至少与尼古拉单抗和派姆单抗有关。抗PD-L1 mAb的PK /药效学（PD）数据很少，但已描述了这些药物随时间变化的清除率，而atezolizumab观察到的高免疫原性可能会影响PK参数，应进一步研究。这些数据表明需要进行额外的PK / PD研究。在这篇综述中，我们总结了免疫检查点抑制剂的PKs的研究，探索了与PD考虑因素的可能相互作用。