Bristol-Myers Squibb, Princeton, New Jersey, USA.
CPT Pharmacometrics Syst Pharmacol. 2020 Jan;9(1):29-39. doi: 10.1002/psp4.12477. Epub 2019 Dec 1.
Ipilimumab is a fully human monoclonal antibody approved for the treatment of melanoma as monotherapy and for the treatment of melanoma, renal cell carcinoma, and colorectal cancer in combination with nivolumab. Ipilimumab time-varying clearance (CL) was assessed by a population pharmacokinetics (PPK) model developed using statistically significant covariates identified in a previous PPK analysis plus additional covariates. Data from 3,411 patients who received ipilimumab 0.3-10 mg/kg alone or in combination with nivolumab in 16 clinical trials were analyzed. Ipilimumab CL decreased over time; the change in CL was greater in patients treated with nivolumab combination than ipilimumab alone and in responders vs. nonresponders. Time-varying covariates including body weight, lactate dehydrogenase, albumin, and performance status were evaluated on change in ipilimumab CL. In addition, ipilimumab CL was similar across different tumor types, nivolumab dosing regimens, and lines of therapy. These data suggest an association of ipilimumab CL with disease severity.
依匹单抗是一种全人源单克隆抗体，已被批准用于治疗黑色素瘤的单药治疗，以及与纳武单抗联合用于治疗黑色素瘤、肾细胞癌和结直肠癌。通过对先前的群体药代动力学（PPK）分析中确定的具有统计学意义的协变量加上其他附加协变量进行分析，建立了依匹单抗时变清除率（CL）的群体药代动力学（PPK）模型进行评估。对来自 16 项临床试验中 3411 名接受依匹单抗 0.3-10mg/kg 单药或联合纳武单抗治疗的患者的数据进行了分析。依匹单抗 CL 随时间降低；与接受依匹单抗单药治疗相比，接受纳武单抗联合治疗的患者以及应答者与无应答者的 CL 变化更大。对依匹单抗 CL 变化的体重、乳酸脱氢酶、白蛋白和表现状态等时变协变量进行了评估。此外，依匹单抗 CL 在不同的肿瘤类型、纳武单抗给药方案和治疗线中相似。这些数据表明依匹单抗 CL 与疾病严重程度有关。
