Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: 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. Results: 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% CI: 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. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
目的： 评估恩沃利单抗单药治疗中国晚期实体瘤患者的初步疗效及安全性。 方法： 研究为一项开放、多中心、剂量递增和剂量扩展的前瞻性Ⅰ期临床研究，剂量递增阶段采用改良的"3+3"设计在6个剂量组(0.1~10.0 mg/kg)中进行，皮下注射每周给药1次。剂量扩展阶段分别在2.5和5.0 mg/kg剂量组进行。 结果： 截至2019年9月2日，共287例实体瘤患者入组并接受恩沃利单抗治疗。在剂量递增阶段未观察到剂量限制性不良反应。所有级别和3~4级药物相关治疗期间不良事件发生率分别为75.3%(216/287)和20.6%(59/287)。所有级别的免疫相关不良反应发生率为24.0%(69/287)，常见免疫相关不良反应(发生率≥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。3.8%(11/287)的患者发生注射部位反应，均为1~2级。在216例疗效可评估的患者中，客观缓解率和疾病控制率分别为11.6%和43.1%，中位缓解持续时间为49.1周(95% CI：24.0~49.3周)。药代动力学结果显示，恩沃利单抗的体内暴露量与剂量成正比，达到血药峰浓度的时间为72~120 h。 结论： 皮下注射恩沃利单抗显示出良好的安全性和初步抗肿瘤活性。.
Keywords: Anti-programmed death-ligand 1 antibody; Efficacy; Envafolimab; Malignant tumor; Safety.