START Center for Cancer Care, San Antonio, Texas.
Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Clin Cancer Res. 2017 Sep 15;23(18):5349-5357. doi: 10.1158/1078-0432.CCR-17-1243. Epub 2017 Jun 20.
This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event continual reassessment method. Twenty-three patients received combination treatment with no dose-limiting toxicities. Treatment-emergent adverse events were mostly grades 1 to 2, without any treatment-related discontinuations. Six patients (26.1%) had confirmed complete or partial responses. Pharmacokinetics and immunogenicity of utomilumab and pembrolizumab were similar when administered alone or in combination. A trend toward higher levels of activated memory/effector peripheral blood CD8 T cells was observed in responders versus nonresponders. The safety, tolerability, and clinical activity demonstrated by utomilumab in combination with pembrolizumab support further investigation in patients with advanced solid tumors. .
这项 Ib 期研究（NCT02179918）评估了 utomilumab 的安全性、抗肿瘤活性、药代动力学和药效学，utomilumab 是一种完全人源 IgG2 mAb，激动剂为 T 细胞共刺激受体 4-1BB/CD137，与人类化、PD-1 阻断 IgG4 mAb 派姆单抗联合用于晚期实体瘤患者。utomilumab（0.45-5.0mg/kg）和派姆单抗（2mg/kg）每 3 周静脉输注一次。utomilumab 剂量递增采用时间事件连续评估方法。23 名患者接受了联合治疗，没有剂量限制毒性。治疗出现的不良反应大多为 1 至 2 级，没有任何与治疗相关的停药。6 名患者（26.1%）有确认的完全或部分缓解。当单独或联合使用时，utomilumab 和派姆单抗的药代动力学和免疫原性相似。与无应答者相比，应答者外周血中激活的记忆/效应 CD8 T 细胞水平较高。utomilumab 与派姆单抗联合使用的安全性、耐受性和临床活性为晚期实体瘤患者的进一步研究提供了支持。
