肿瘤免疫治疗药物相关种属选择的一般考虑

General considerations on the selection of relevant species for immune - oncology drugs

肿瘤免疫基础研究和临床研究的快速发展使越来越多的新疗法成为可能,新的免疫检查点抑制剂、共刺激分子激动剂(本文中统称为肿瘤免疫治疗药物)以及以此为基础的联合用药展现了未来的研究方向。由于这类药物的生物活性大多具有较高的种属特异性,健康动物中目标靶点的表达特性与人体疾病状态(或疾病部位)下的表达特性存在较大差异。因此,非临床安全性评价中的一个主要挑战是确定能够预测临床风险尤其是免疫相关不良事件(irAEs)的相关种属或/动物模型。本文分析了肿瘤免疫治疗药物非临床安全性评价中存在的挑战,并结合ICH S6(R1)指南和帕博利珠单抗非临床研究案例简述了相关种属选择时的一般考虑,供申请人和监管机构关注或参考。

The rapid development of fundamental and clinical researches on immune-oncology makes more promising new therapies available.Novel immune checkpoint inhibitors and co-stimulatory molecule agonists(referred as immune-oncology drugs in this paper),as well as the combinations of these monotherapy drugs,are believed to represent the future research direction.Since most biological activities of these drugs are highly species-specific,and significant difference of target expression levels may exist between healthy animals and humans,a major challenge in the non-clinical safety evaluation of this kind of drugs is to identify relevant species that can predict the drug-related risks in human use,especially immune-related adverse events(irAEs).In this paper,the challenges in non-clinical safety evaluation of immune-oncology drugs were reviewed,the non-clinical development program of pembrolizumab were also discussed and the general considerations on the selection of relevant species were summarized based on the guidance of ICH S6(R1),hoping to draw attentions and provide references on this issue for researchers and regulators.