替拉戈单抗联合阿特珠单抗治疗中国晚期实体瘤患者的药代动力学、安全性和初步疗效的 I 期研究。

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-07-01 Epub Date: 2024-03-07 DOI:10.1007/s00280-024-04650-y
Colby S Shemesh, Yongsheng Wang, Andrew An, Hao Ding, Phyllis Chan, Qi Liu, Yih-Wen Chen, Benjamin Wu, Qiong Wu, Xian Wang
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引用次数: 0

摘要

目的:Tiragolumab 是一种免疫球蛋白 G1 单克隆抗体,靶向具有免疫球蛋白和免疫受体 ITIM 结构域的免疫检查点 T 细胞免疫受体。靶向多种免疫途径可改善抗肿瘤反应。YP42514 I期研究评估了替拉戈单抗联合阿特珠单抗在中国晚期实体瘤患者中的药代动力学(PK)、安全性和初步疗效:方法: 符合条件的中国大陆成人患者均为东部合作肿瘤学组(Eastern Cooperative Oncology Group)表现评分为0/1分、预期寿命≥12周且血液学/内脏器官功能正常。患者每3周接受一次tiragolumab 600毫克和atezolizumab 1200毫克静脉注射。主要终点是PK(替拉戈单抗和阿特珠单抗的血清浓度)和安全性。这项研究的结果与全球 I 期研究 GO30103(NCT02794571)的结果进行了比较:在这项研究中,20 名患者接受了中位数为 5 个剂量的替拉戈单抗和阿特珠单抗治疗。中位年龄为57.5岁,85.0%的患者为男性,最常见的肿瘤类型为非小细胞肺癌。中国患者的暴露量与全球GO30103人群相当:第1周期替拉单抗浓度-时间曲线下面积的几何平均比值为1.07,0-21;第1周期阿特珠单抗暴露峰值和谷值的几何平均比值分别为0.92和0.93。在中国和全球人群中,治疗相关不良事件的发生率一致。本研究中有两名患者(10.0%)获得了部分应答:结论:在这项研究中,替拉戈单抗联合阿特佐利珠单抗具有耐受性,并显示出初步的抗肿瘤活性。在中国和全球人群中,替拉戈单抗联合阿特珠单抗的PK和安全性没有明显差异:中国临床试验注册编号:CTR20210219/YP42514。注册日期:2021年3月16日。
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Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.

Purpose: Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors.

Methods: Adult patients from mainland China with Eastern Cooperative Oncology Group performance score 0/1, life expectancy of ≥ 12 weeks, and adequate hematologic/end organ function were eligible. Patients received tiragolumab 600 mg and atezolizumab 1200 mg intravenous every 3 weeks. Key endpoints were PK (serum concentrations of tiragolumab and atezolizumab) and safety. Results from this study were compared with the global phase I study, GO30103 (NCT02794571).

Results: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of patients were male and the most common tumor type was non-small cell lung cancer. Exposures in Chinese patients were comparable to the global GO30103 population: geometric mean ratio was 1.07 for Cycle 1 tiragolumab area under the concentration-time curve0-21 and 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. Treatment-related adverse events were consistent across the Chinese and global populations. Two patients (10.0%) in this study achieved a partial response.

Conclusion: In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations.

Clinical trial registration number: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021.

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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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