Lessons learned: This pharmacokinetic study of nivolumab showed that there is little ethnic difference in the handling of nivolumab.Nivolumab was well tolerated in Korean patients.
Background: This phase I study of nivolumab, an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody, investigated the pharmacokinetics and safety of nivolumab in Korean patients with advanced solid tumors. Findings were compared with results from Japan and the U.S.
Materials and methods: In this two-part study, patients received a single dose of nivolumab (1, 3, and 10 mg/kg; ONO-4538-13) and were followed up for 3 weeks. Those who met the required criteria proceeded to the second part (ONO-4538-14), and received the same dose as in part one every 2 weeks.
Results: Six patients per dose level were enrolled (n = 18). The mean elimination half-life of nivolumab among the groups ranged from 15.0 to 19.1 days. The maximum serum concentration and area under serum concentration-time curve increased almost dose-proportionally at doses from 1 to 10 mg/kg. Adverse drug reactions (ADRs; mostly grade ≤2) were reported in seven patients (38.9%). ADRs grade ≥3 occurred in one patient (5.6%; pneumonitis). Three patients (16.7%) developed ADRs related to thyroid dysfunction.
Conclusion: The pharmacokinetic parameters of nivolumab were similar among patients from Korea, Japan, and the U.S. The safety profile was consistent with findings from previous studies.
经验总结
• nivolumab的药代动力学研究显示nivolumab的体内代谢几乎没有种族差异。
• 韩国患者对nivolumab的耐受性良好。
摘要
背景.此nivolumab [一种抗程序性细胞死亡蛋白‐1（抗‐PD‐1）单克隆抗体] I期研究考察了nivolumab在韩国晚期实体瘤患者中的药代动力学和安全性。我们将研究结果与日本和美国的结果进行了比较。
材料与方法.在这个由两部分组成的研究中, 患者接受nivolumab单次给药（1、3和10 mg/kg；ONO‐4538‐13）, 随访3周。那些符合所要求标准的受试者进入第二部分（ONO‐4538‐14）, 每两周接受一次与第一部分中相同的剂量。
结果.每种剂量水平入组六名患者（n=18）。nivolumab的平均消除半衰期介于15.0至19.1天之间。最大血清浓度和血清浓度‐时间曲线下面积在1至10 mg/kg的剂量下几乎与剂量成比例增加。有7例患者（38.9%）报告了药品不良反应（ADR；大多数≤2级）。有1例患者（5.6%）发生了≥3级的ADR（肺炎）。有3例患者（16.7%）发生了与甲状腺功能不全有关的ADR。
结论.来自韩国、日本和美国的患者的nivolumab药代动力学参数相似。安全性特征与以前的研究结果一致。
Trial registration: ClinicalTrials.gov NCT02261285 NCT02261298.
© AlphaMed Press; the data published online to support this summary is the property of the authors.