Brahmer Julie R, Hammers Hans, Lipson Evan J
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Future Oncol. 2015;11(9):1307-26. doi: 10.2217/fon.15.52. Epub 2015 Mar 23.
Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Nivolumab is approved in Japan and the USA for the treatment of patients with advanced melanoma. A Phase I trial reported overall objective response rates of 17, 32 and 29% in patients with advanced non-small-cell lung cancer, melanoma and renal cell carcinoma, respectively, which included many heavily pretreated patients. 1-/2-year overall survival rates were 42%/24%, 63%/48% and 70%/50% for non-small-cell lung cancer, melanoma and renal cell carcinoma, respectively. Nivolumab significantly improved survival versus dacarbazine in previously untreated patients with metastatic melanoma in a Phase III trial. Nivolumab is associated with a manageable adverse event profile. Numerous clinical trials are investigating nivolumab alone or in combination with other therapies in multiple cancer settings. This article summarizes the development of nivolumab as of November 2014.
纳武单抗是一种全人源IgG4程序性死亡受体1（PD-1）免疫检查点抑制剂抗体，可阻断PD-1，并通过消除PD-1通路介导的T细胞抑制作用来恢复抗癌免疫反应。纳武单抗在日本和美国被批准用于治疗晚期黑色素瘤患者。一项I期试验报告称，晚期非小细胞肺癌、黑色素瘤和肾细胞癌患者的总体客观缓解率分别为17%、32%和29%，其中包括许多经过大量预处理的患者。非小细胞肺癌、黑色素瘤和肾细胞癌的1/2年总生存率分别为42%/24%、63%/48%和70%/50%。在一项III期试验中，纳武单抗与达卡巴嗪相比，显著提高了先前未治疗的转移性黑色素瘤患者的生存率。纳武单抗的不良事件情况可控。众多临床试验正在研究纳武单抗单独或与其他疗法联合用于多种癌症的治疗。本文总结了截至2014年11月纳武单抗的研发情况。
