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Pharmacological Effects and Clinical Evaluation of PD-1 Inhibitor of Tislelizumab in the Treatment of Advanced Malignant Tumors
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摘要: 近年来, 免疫治疗在恶性肿瘤领域取得了革命性突破, 越来越多的新型免疫检查点抑制剂问世, 彻底改变了恶性肿瘤的一线、二线和后线治疗选择。替雷利珠单抗是中国自主研发的PD-1抑制剂, 该药在经典型霍奇金淋巴瘤、尿路上皮癌、非小细胞肺癌、肝细胞癌、食管鳞状细胞癌和胃癌/胃食管交界癌等肿瘤治疗中均表现出良好的抗肿瘤潜力和安全性。本文就替雷利珠单抗的结构与作用机制、药效学与药代动力学、临床研究及不良反应等方面的最新进展进行阐述, 以期为临床医师提供借鉴和参考。Abstract: In recent years, immunotherapy has made breakthroughs in the field of malignant tumors, and more and more novel immune checkpoint inhibitors have been developed, revolutionizing the first-line, second-line and post-line treatment options for malignant tumors. Tislelizumab is a domestically developed inhibitor of programmed death-1 (PD-1). The drug has shown good antitumor potential and safety in classical Hodgkin's lymphoma, uroepithelial carcinoma, non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma and gastric cancer/gastroesophageal junction carcinoma. In this review, the structure and mechanism of action, pharmacodynamics and pharmacokinetics, clinical research and adverse reactions of tislelizumab are reviewed to provide reference for clinical application.
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Key words:
- malignant tumor /
- PD-1 inhibitor /
- tislelizumab /
- immunotherapy
作者贡献：罗详冲负责文献检索和论文撰写；王周清、李琼艳、毛贵兵、安乐、朱家宏、陶娥红、孙丽飞、王胜飞负责文献资料收集；李高峰负责写作指导和论文修订。利益冲突：所有作者均声明不存在利益冲突 -
表 1 正在开展的替雷利珠单抗治疗晚期恶性肿瘤患者的临床试验研究
NCT编号 试验方案 试验阶段 NCT03967977，BGB-A317-310 替雷利珠单抗联合顺铂或卡铂和吉西他滨作为局部晚期或转移性尿路上皮癌一线治疗的临床试验研究 Ⅲ期 NCT03412773，BGB-A317-301 比较替雷利珠单抗与索拉非尼作为不可切除肝细胞癌一线治疗的疗效和安全性的临床试验研究 Ⅲ期 NCT03430843，BGB-A317-302 比较替雷利珠单抗与化疗作为二线治疗用于晚期不可切除或转移性食管鳞状细胞癌患者的疗效的临床试验研究 Ⅲ期 NCT03783442，BGB-A317-306 替雷利珠单抗联合化疗作为一线治疗用于不可切除的局部晚期或转移性食管鳞状细胞癌患者的疗效和安全性的临床试验研究 Ⅲ期 NCT03957590，BGB-A317-311 替雷利珠单抗与安慰剂联合同步放化疗治疗局限性食管癌患者的临床试验研究 Ⅲ期 NCT03777657，BGB-A317-305 替雷利珠单抗联合铂类和氟尿嘧啶与安慰剂联合铂类和氟尿嘧啶作为一线治疗用于局部晚期不可切除或转移性胃或胃食管交界腺癌患者的疗效和安全性的临床试验研究 Ⅲ期 NCT03924986，BGB-A317-309 比较替雷利珠单抗联合化疗与单纯化疗用于复发或转移性鼻咽癌一线治疗的疗效和安全性的临床试验研究 Ⅲ期 NCT03594747，BGB-A317-307 比较替雷利珠单抗联合紫杉醇+卡铂或白蛋白紫杉醇+卡铂与单独紫杉醇+卡铂作为一线治疗用于晚期鳞状非小细胞肺癌的疗效和安全性的临床试验研究 Ⅲ期 NCT03663205，BGB-A317-304 比较替雷利珠单抗联合化疗与单纯化疗作为一线治疗用于晚期非鳞状非小细胞肺癌的临床试验研究 Ⅲ期 NCT03358875，BGB-A317-303 替雷利珠单抗与多西紫杉醇用于既往含铂方案进展的非小细胞肺癌患者的疗效和安全性的临床试验研究 Ⅲ期 NCT04005716，BGB-A317-312 比较替雷利珠单抗单药与联合铂类+依托泊苷用于广泛期小细胞肺癌的临床试验研究 Ⅲ期 NCT04004221，BGB-A317-204 替雷利珠单抗用于既往接受过治疗的PD-L1阳性的局部晚期或转移性尿路上皮癌的临床试验研究 Ⅱ期 NCT03419897，BGB-A317-208 替雷利珠单抗在既往接受过治疗的不可切除肝细胞癌患者中的疗效、安全性和药代动力学临床试验研究 Ⅱ期 NCT03736889，BGB-A317-209 替雷利珠单抗用于局部晚期不可切除或转移性高微卫星不稳定性或错配修复缺陷实体肿瘤患者的单药治疗临床试验研究 Ⅱ期 PD-L1：程序性死亡[蛋白]配体-1 
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