Liu R R, Gu S Z, Zhou T, Lin L Z, Chen W C, Zhong D S, Liu T S, Yang N, Shen L, Xu S Y, Lu N, Zhang Y, Gong Z L, Xu J M
Department of Medical Oncology, Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing 100071, China.
Department of Interventional Radiology, Hunan Cancer Hospital, Changsha 410031, China.
Zhonghua Zhong Liu Za Zhi. 2023 Oct 23;45(10):898-903. doi: 10.3760/cma.j.cn112152-20220530-00373.
To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
评估恩沃利单抗单药治疗中国晚期实体瘤患者的安全性和抗肿瘤活性。这项开放标签、多中心的I期试验包括剂量爬坡和剂量扩展阶段。在剂量爬坡阶段，患者按照改良的“3+3”设计，每周一次皮下注射0.1、0.3、1.0、2.5、5.0或10.0mg/kg恩沃利单抗。剂量扩展阶段在2.5mg/kg和5.0mg/kg（每周一次）剂量组中进行。截至2019年11月25日，共有287例患者接受了恩沃利单抗治疗。在剂量爬坡阶段，未观察到剂量限制性毒性（DLT）。在所有剂量组中，所有级别的药物相关治疗中出现的不良事件（TEAE）发生在75.3%的患者中，3级或4级发生在20.6%的患者中。所有级别的免疫相关不良反应（irAE）发生率为24.0%，最常见的irAE（≥2%）包括甲状腺功能减退、甲状腺功能亢进、免疫相关性肝炎和皮疹。注射部位反应的发生率较低（3.8%），均为1-2级。在216例可评估疗效的患者中，客观缓解率（ORR）和疾病控制率（DCR）分别为11.6%和43.1%。中位缓解持续时间为49.1周（95%置信区间24.0，49.3）。根据研究剂量爬坡阶段的药代动力学（PK）结果，恩沃利单抗的PK暴露与剂量成正比，达到最大血浆浓度的中位时间为72-120小时。皮下注射恩沃利单抗在中国晚期实体瘤患者中具有良好的安全性和有前景的初步抗肿瘤活性。
