替雷利珠单抗联合阿替利珠单抗在中国晚期实体瘤患者中的 I 期药代动力学、安全性和初步疗效研究。
Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.
机构信息
Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.
Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China.
出版信息
Cancer Chemother Pharmacol. 2024 Jul;94(1):45-55. doi: 10.1007/s00280-024-04650-y. Epub 2024 Mar 7.
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 curve 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.
目的
替雷利珠单抗是一种免疫球蛋白 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 T 细胞免疫受体。靶向多种免疫途径可能会提高抗肿瘤反应。I 期 YP42514 研究评估了替雷利珠单抗联合阿特珠单抗在中国大陆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
符合条件的患者为来自中国大陆的、东部肿瘤协作组体力状态评分为 0/1、预期寿命≥12 周且血液学/终末器官功能充足的成年患者。患者接受替雷利珠单抗 600mg 和阿特珠单抗 1200mg 静脉输注，每 3 周一次。主要终点是 PK（替雷利珠单抗和阿特珠单抗的血清浓度）和安全性。本研究结果与全球 I 期研究 GO30103（NCT02794571）进行了比较。
结果
在这项研究中，20 名患者接受了中位数为 5 个周期的替雷利珠单抗联合阿特珠单抗治疗。中位年龄为 57.5 岁，85.0%的患者为男性，最常见的肿瘤类型是非小细胞肺癌。中国患者的暴露情况与全球 GO30103 人群相当：替雷利珠单抗第 1 周期的曲线下面积的几何均数比为 1.07，第 1 周期的峰值和谷值阿特珠单抗暴露的几何均数比分别为 0.92 和 0.93。研究药物相关的不良反应在中、全球人群中一致。本研究中有 2 名患者（10.0%）获得部分缓解。
结论
在这项研究中，替雷利珠单抗联合阿特珠单抗是可以耐受的，并显示出初步的抗肿瘤活性。替雷利珠单抗联合阿特珠单抗在中、全球人群中的 PK 或安全性无明显差异。
临床试验注册
中国临床试验注册中心标识符 CTR20210219/YP42514。注册日期 2021 年 3 月 16 日。
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