Lessons learned: Nivolumab treatment at doses of 3 mg/kg once every 2 weeks (Q2W), 240 mg Q2W, and 360 mg once every 3 weeks was well tolerated in the Chinese population, with no new safety signals identified.Comparison of intensive pharmacokinetic profiles of nivolumab at 3 mg/kg Q2W in Chinese versus global populations revealed no ethnic differences of nivolumab treatment.Nivolumab shows promising preliminary antitumor activity in nasopharyngeal carcinoma.
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.
经验总结
纳武单抗治疗剂量每 2 周 (Q2W) 3 mg/kg、240 mg Q2W、360 mg Q3W 的用药方式在中国人群中耐受性良好，没有发现新的安全信号。
对比 3 mg/kg Q2W 纳武单抗用药方式在中国与全球人群中的强化药代动力学特征，结果显示，纳武单抗治疗没有种族差异。
纳武单抗在鼻咽癌治疗中，具有良好的初步抗肿瘤活性。
摘要
背景。本项 I/II 期研究探讨了纳武单抗(抗程序性细胞死亡‐1 单克隆抗体)在中国鼻咽癌 (NPC)及其他实体肿瘤患者中的安全性与药代动力学 (PK) 特征。
方法。剂量评估阶段 [每 2 周(Q2W) 3 mg/kg]之后，开展队列扩展(3 mg/kg/Q2W 或 240 mg Q2W 或每 3 周 360 mg 的固定剂量)。
结果。在剂量评估阶段，8/8 例患者完成了第一个疗程，未出现剂量限制性毒性。数据截止时，46/51 名患者接受了安全性评估(所有队列)。35 例 (76%) 患者产生治疗相关不良事件 (TRAE)，以 1‐2 级事件为主；1 例 (3 mg/kg Q2W) 因产生研究药物毒性而停药。3mg/kg，240 mg 和 360 mg强化PK特性在单剂量和多剂量纳武单抗得到良好表征。6 例 (6/46) 患者出现客观反应，4 例 (4/32) 为NPC。
结论。纳武单抗 3mg /kg、和 240 mg、360 mg 固定剂量单药治疗在中国患者中耐受性良好，3mg/kg 的 PK 分析结果与全球患者相似。初步疗效表明，纳武单抗对晚期NPC具有良好的抗肿瘤活性。
Trial registration: ClinicalTrials.gov NCT02593786.
© AlphaMed Press; the data published online to support this summary are the property of the authors.