Clin Cancer Res:免疫检查点靶向药MEDI0562治疗晚期实体瘤

2020-09-10 QQY MedSci原创

免疫检查点阻断已被证明对多种实体肿瘤有临床益处;但耐药性和复发经常发生,限制了免疫检查点抑制剂的临床应用。现下,我们需要开发在激活的免疫细胞中高表达的新型免疫调节靶点。MEDI0562是一种人源化的激

免疫检查点阻断已被证明对多种实体肿瘤有临床益处;但耐药性和复发经常发生,限制了免疫检查点抑制剂的临床应用。现下,我们需要开发在激活的免疫细胞中高表达的新型免疫调节靶点。MEDI0562是一种人源化的激动型单克隆抗体,可特异性地与协同刺激分子OX40结合。

本研究是一项多中心、开放标签、单臂、剂量递增(3+3设计)的I期临床试验,也是首个评估MEDI0562用于晚期实体瘤成年患者的人体研究。予以患者不同剂量的MEDI0562(0.03、0.1、0.3、1.0、3.0或10 mg/kg·2周)静滴治疗,直到病情进展或出现不可耐受的毒性。主要目的是评估安全性和耐受性。次要终点包括抗肿瘤活性、药效学、免疫原性和药代动力学。

总体上,有55位患者至少接受了1剂量的MEDI0562治疗被纳入分析。最常见的肿瘤类型是头颈鳞状细胞癌(47%)。中位治疗持续时间为10周(范围 2-48周)。治疗相关不良反应(TRAEs)发生于67%的患者,最常见的有疲劳(31%)和输液相关反应(14%)。3级TRAEs发生于14%的患者,无明显剂量相关性;无TRAEs导致的死亡。两位患者出现免疫相关部分缓解,44%的患者病情稳定。MEDI0562治疗可诱导增加外周血的Ki67+CD4+和CD8+记忆T细胞的增殖,并减少瘤内的OX40+FOXXP3+细胞。

MEDI0562用于重症预处理的患者,即使剂量高达10 mg/kg也是安全的,值得进一步进行评估。

原始出处:

Bonnie S. Glisson, et al. Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors. Clinical Cancer Research. September 09, 2020. DOI: 10.1158/1078-0432.CCR-19-3070

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