A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma
A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma
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DOI：
10.1182/blood.2019004701
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发表时间：
2020-11-19
期刊：
影响因子：
20.3
通讯作者：
Ansell, Stephen M.
中科院分区：
文献类型：
--
作者：
Bartlett, Nancy L.;Herrera, Alex F.;Ansell, Stephen M.
在复发/难治性霍奇金淋巴瘤（R/R HL）中，抗程序性死亡-1抑制剂派姆单抗等免疫疗法已经证明了单药治疗的有效性，并且在治疗中发挥着越来越重要的作用。CD30/CD16A双特异性抗体AFM13是一种先天性免疫细胞接合剂，是一种一流的四价抗体，旨在在HL细胞上的CD30和自然杀伤细胞和巨噬细胞上的CD16A受体之间建立桥梁，以诱导肿瘤细胞杀伤。AFM13的早期研究表明，作为R/RHL患者的单药治疗有疗效的迹象，AFM13与派姆单抗联合治疗代表了一种合理的新治疗方式。在这里，我们描述了一项1b期剂量递增研究，以评估AFM13联合派姆单抗治疗R/R HL患者的安全性和初步疗效。主要目的是估计最大耐受剂量；次要目的是评估安全性、耐受性、抗肿瘤疗效、药代动力学和药效学。在这个大量预处理的患者群体中，AFM13和pembrolizumab联合治疗通常耐受性良好，与单独使用每种药物的已知情况相比，安全性相似。AFM13联合派姆单抗在最高治疗剂量下的客观反应率为88%，总体人群的总反应率为83%。AFM13在联合用药条件下的药代动力学评估显示其半衰期高达20.6小时。这一概念验证研究有望成为一种值得进一步研究的新型免疫治疗组合。
In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/RHL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation.