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Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer.
Atezolizumab 在儿童和年轻成人癌症患者中的群体药代动力学、暴露安全性和免疫原性。
Atezolizumab Cancer immunotherapy Clinical pharmacology Exposure-safety Immune checkpoint inhibitor Pediatric oncology Population pharmacokinetics
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摘要

BACKGROUND:The iMATRIX-atezolizumab study was a phase I/II, multicenter, open-label study designed to assess the safety and pharmacokinetics of atezolizumab in pediatric and young adult patients. We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study.
METHODS:Patients aged < 18 years (n = 69) received a weight-adjusted dose of atezolizumab (15 mg/kg every 3 weeks [q3w]; maximum 1200 mg); those aged ≥ 18 years (n = 18) received a flat dose (1200 mg q3w). A prior two-compartment intravenous infusion input adult population-PK (popPK) model of atezolizumab was used as a basis to model pediatric data.
RESULTS:A total of 431 atezolizumab serum concentrations from 87 relapse-refractory pediatric and young adult patients enrolled in the iMATRIX-atezolizumab study were used for the popPK analysis. The dataset comprised predominantly patients aged < 18 years, including two infants aged < 2 years, with a wide body weight and age range. The clearance and volume of distribution estimates of atezolizumab were 0.217 L/day and 3.01 L, respectively. Atezolizumab geometric mean trough exposures were ~ 20% lower in pediatric patients versus young adults; this was not clinically meaningful as both groups achieved the target concentration (6 μg/mL). Safety was similar between pediatric and young adult patients with no exposure-safety relationship observed. Limited responses (4/87) precluded an exposure-response assessment on outcomes. A comparable rate (13% vs 11%) of atezolizumab anti-drug antibodies was seen in pediatric and young adult patients.
CONCLUSIONS:These findings demonstrate a similar exposure-safety profile of atezolizumab in pediatric and young adult patients, supportive of weight-based dosing in pediatric patients.
TRIAL REGISTRATION:NCT02541604.

译文

背景: iMATRIX-atezolizumab 研究是一项 I/II 期、多中心、开放标签研究,旨在评估 atezolizumab 在儿童和年轻成人患者中的安全性和药代动力学。我们描述了 atezolizumab 在患有转移性实体瘤或血液恶性肿瘤的儿童和年轻人中的药代动力学 (PK) 、暴露安全性和免疫原性。
方法: 年龄 <18 岁的患者 (n = 69) 接受体重调整剂量的阿特唑珠单抗 (每 3 周 15 毫克/千克 [q3w]; 最大 1200 毫克); 那些年龄 ≥ 18 岁 (n =-18) 的人接受了统一剂量 (1200-mg q3w)。阿特唑珠单抗先前的二室静脉输注成人人群 PK (popk) 模型被用作建立儿科数据模型的基础。
结果: 在 iMATRIX-atezolizumab 研究中登记的 87 名复发难治的儿童和年轻成人患者的 431 份 atezolizumab 血清浓度被用于 popk 分析。该数据集主要包括年龄 <18 岁的患者,包括两名体重和年龄范围较宽的 <2 岁的婴儿。Atezolizumab 的清除率和分布估计量分别为 0.217 l/天和 3.01 l/天。Atezolizumab 几何平均谷暴露在儿童患者与年轻人中降低约 20%; 这在临床上没有意义,因为两组都达到了目标浓度 (6 μ g/mL)。没有观察到暴露-安全关系的儿童和年轻成年患者之间的安全性相似。有限的反应 (4/87) 排除了对结果的暴露反应评估。在儿童和年轻成人患者中,atezolizumab 抗药物抗体的比例相当 (13% vs 11%)。
结论: 这些发现证明了阿特唑珠单抗在儿童和年轻成年患者中的暴露安全性相似,支持了在儿童患者中基于体重的剂量。
试用注册: nct02541604。

Atezolizumab

肿瘤 肺癌、膀胱癌、乳腺癌 药物
概述  :  

Atezolizumab(阿特朱单抗,Tecentriq)是人源化拮抗PD-L1的单克隆Ig G4抗体,是罗氏(Roche)研发生产,于2016年10月18日FDA批准的用于治疗在含铂化疗期间或之后病情恶化的转移性非小细胞肺癌的PD-L1单克隆抗体药物。   作为第一个上市的PD-L1抗体,Atezolizumab和传统的化疗药物相比,发生严重副作用的几率大大降低。凭借出色的临床数据,已经被FDA批准用于膀胱癌和非小细胞肺癌的二线治疗,成为继PD-1抗体Keytruda和Opdi

Atezolizumab

释    义   n. 阿特朱单抗

例    句   A combination of nivolumab and ipilimumab had the highest risk for colitis, while pembrolizumab and atezolizumab had a lower possibility than the other ICIs. 纳武单抗和易普利姆玛的结肠炎风险最高,而派姆单抗和阿特珠单抗的结肠炎风险低于其他免疫检查点抑制剂。

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