A Phase I/II Open-Label Study of Nivolumab in Previously Treated Advanced or Recurrent Nasopharyngeal Carcinoma and Other Solid Tumors
A Phase I/II Open-Label Study of Nivolumab in Previously Treated Advanced or Recurrent Nasopharyngeal Carcinoma and Other Solid Tumors
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DOI：
10.1634/theoncologist.2019-0284
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发表时间：
2019-07-01
期刊：
影响因子：
5.8
通讯作者：
Zhang, Li
中科院分区：
文献类型：
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作者：
Ma, Yuxiang;Fang, Wenfeng;Zhang, Li
背景 这项 I/II 期研究调查了纳武单抗（抗程序性细胞死亡 1 单克隆抗体）在中国鼻咽癌 (NPC) 和其他实体瘤患者中的安全性和药代动力学 (PK)。方法 剂量评估阶段（3 mg/kg 每 2 周一次 [Q2W]）之后是队列扩展阶段（3 mg/kg Q2W 或 240 mg Q2W 的固定剂量或 360 mg 每 3 周一次）。结果 在剂量评估阶段，8/8 的患者完成了一个周期，没有出现剂量限制性毒性。在数据截止时，46/51 名患者可进行安全性评估（所有队列）。 35 名患者 (76%) 发生了治疗相关不良事件 (TRAE)，主要为 1-2 级；一名患者（3 mg/kg Q2W）因研究药物毒性而停药。单剂量和多剂量纳武单抗的 3 mg/kg、240 mg 和 360 mg 强化 PK 曲线得到了很好的表征。在六名 (6/46) 名患者中确定了客观缓解，其中四名 (4/32) 患有鼻咽癌肿瘤。结论 3 mg/kg 的纳武单抗单药治疗以及 240 mg 和 360 mg 的固定剂量在中国患者群体中具有良好的耐受性，3 mg/kg 的 PK 曲线与全球患者相似。初步疗效结果显示纳武单抗在晚期鼻咽癌中具有良好的抗肿瘤活性。
Background This phase I/II study investigated the safety and pharmacokinetics (PK) of nivolumab (anti-programmed cell death-1 monoclonal antibody) in Chinese patients with nasopharyngeal carcinoma (NPC) and other solid tumors. Methods A dose evaluation phase (3 mg/kg once every 2 weeks [Q2W]) was followed by a cohort expansion phase (3 mg/kg Q2W or flat doses of 240 mg Q2W or 360 mg once every 3 weeks). Results In the dose evaluation phase, 8/8 patients completed one cycle with no dose-limiting toxicities. At data cutoff, 46/51 patients were evaluable for safety (all cohorts). Treatment-related adverse events (TRAEs) occurred in 35 (76%) patients and were primarily grade 1-2; one patient (3 mg/kg Q2W) discontinued because of study drug toxicity. Intensive PK profiles at 3 mg/kg, 240 mg, and 360 mg were well characterized at single and multiple doses of nivolumab. An objective response was determined in six (6/46) patients, four (4/32) of whom had NPC tumors. Conclusion Nivolumab monotherapy at 3 mg/kg and flat doses of 240 mg and 360 mg were well tolerated in this Chinese patient population, with PK profiles at 3 mg/kg being similar to those of global patients. Preliminary efficacy results showed promising antitumor activity of nivolumab in advanced NPC.