皮下注射恩沃利单抗治疗中国晚期实体瘤的Ⅰ期临床研究
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%(6...
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| Published in | 中华肿瘤杂志 Vol. 45; no. 10; pp. 898 - 903 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
解放军总医院第五医学中心肿瘤学部肿瘤内科，北京 100071%湖南省肿瘤医院介入科，长沙 410031%解放军海军军医大学第一附属医院泌尿外科，上海 200433%广州中医药大学第一附属医院肿瘤中心，广州 510405%苏州大学附属第一医院消化内科，苏州 215006%天津医科大学总医院肿瘤内科，天津 300052%复旦大学附属中山医院肿瘤内科，上海 200032%湖南省肿瘤医院肺胃肠内科，长沙 410031%北京大学肿瘤医院消化肿瘤内科，北京 100142%四川思路康瑞药业有限公司，成都 610036
01.10.2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0253-3766 |
| DOI | 10.3760/cma.j.cn112152-20220530-00373 |
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| Abstract | 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。 |
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| AbstractList | 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。 |
| Abstract_FL | 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. |
| Author | 沈琳 卢妮 钟殿胜 张允 龚兆龙 刘容锐 周铁 林丽珠 徐建明 陈卫昌 杨农 刘天舒 古善智 徐司颖 |
| AuthorAffiliation | 解放军总医院第五医学中心肿瘤学部肿瘤内科，北京 100071%湖南省肿瘤医院介入科，长沙 410031%解放军海军军医大学第一附属医院泌尿外科，上海 200433%广州中医药大学第一附属医院肿瘤中心，广州 510405%苏州大学附属第一医院消化内科，苏州 215006%天津医科大学总医院肿瘤内科，天津 300052%复旦大学附属中山医院肿瘤内科，上海 200032%湖南省肿瘤医院肺胃肠内科，长沙 410031%北京大学肿瘤医院消化肿瘤内科，北京 100142%四川思路康瑞药业有限公司，成都 610036 |
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| Author_FL | Zhong Diansheng Liu Tianshu Zhang Yun Yang Nong Xu Jianming Lin Lizhu Shen Lin Liu Rongrui Gong Zhaolong Gu Shanzhi Chen Weichang Lu Ni Zhou Tie Xu Siying |
| Author_FL_xml | – sequence: 1 fullname: Liu Rongrui – sequence: 2 fullname: Gu Shanzhi – sequence: 3 fullname: Zhou Tie – sequence: 4 fullname: Lin Lizhu – sequence: 5 fullname: Chen Weichang – sequence: 6 fullname: Zhong Diansheng – sequence: 7 fullname: Liu Tianshu – sequence: 8 fullname: Yang Nong – sequence: 9 fullname: Shen Lin – sequence: 10 fullname: Xu Siying – sequence: 11 fullname: Lu Ni – sequence: 12 fullname: Zhang Yun – sequence: 13 fullname: Gong Zhaolong – sequence: 14 fullname: Xu Jianming |
| Author_xml | – sequence: 1 fullname: 刘容锐 – sequence: 2 fullname: 古善智 – sequence: 3 fullname: 周铁 – sequence: 4 fullname: 林丽珠 – sequence: 5 fullname: 陈卫昌 – sequence: 6 fullname: 钟殿胜 – sequence: 7 fullname: 刘天舒 – sequence: 8 fullname: 杨农 – sequence: 9 fullname: 沈琳 – sequence: 10 fullname: 徐司颖 – sequence: 11 fullname: 卢妮 – sequence: 12 fullname: 张允 – sequence: 13 fullname: 龚兆龙 – sequence: 14 fullname: 徐建明 |
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| Keywords | 恶性肿瘤 抗程序性死亡受体配体1抗体 安全性 Efficacy 恩沃利单抗 Malignant tumor Safety Envafolimab Anti-programmed death-ligand 1 antibody 疗效 |
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