Liu Weiping, Ping Lingyan, Xie Yan, Sun Yingli, Du Tingting, Niu Yi, Cisternas Galia, Huang Funan, Garcia-Vargas Jose, Childs Barrett H, Mehra Aruna, Reschke Susanne, Wang Xiaopei, Song Yuqin, Zhu Jun
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, No.52 Fucheng Road, Haidian District, Beijing, 100142, China.
Bayer HealthCare Co. Ltd., Beijing, China.
Cancer Chemother Pharmacol. 2022 Jun;89(6):825-831. doi: 10.1007/s00280-022-04417-3. Epub 2022 Mar 23.
Copanlisib, a pan-PI3K inhibitor, has previously shown clinical efficacy and a tolerable safety profile in patients with indolent non-Hodgkin lymphoma. However, the pharmacokinetics, safety, tolerability, and efficacy of copanlisib in Chinese patients have not been reported.
This was a single-arm, open-label, phase I study of copanlisib in Chinese patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). Patients received a single intravenous 60 mg infusion of copanlisib over 1 h on days 1, 8, and 15 of a 28-day cycle, with 1 week of rest. Safety was monitored throughout the study, and plasma copanlisib levels were measured for pharmacokinetic analysis. Tumor response was determined by independent central radiologic review.
Sixteen patients were enrolled and 13 were treated with 60 mg of copanlisib for a median of 15.0 weeks. With a C of 566 μg/L and a AUC (0-24) of 1880 μg·h/L following single intravenous infusion, the pharmacokinetic parameters of copanlisib were consistent with that in previous studies, and no accumulation in plasma was observed. Treatment-emergent adverse events were reported for all 13 patients, the most common of which were hyperglycemia (100.0%), hypertension (76.9%), decreased neutrophil count (76.9%), and decreased white blood cell count (69.2%). Seven out of 12 evaluated patients achieved partial response, resulting in an overall response rate of 58.3% CONCLUSIONS: Copanlisib was well tolerated in Chinese patients with relapsed or refractory iNHL at the dose of 60 mg and demonstrated encouraging disease control, thus warranting further clinical investigation.
NCT03498430 (April 13, 2018).
库潘尼西是一种泛PI3K抑制剂，此前已在惰性非霍奇金淋巴瘤患者中显示出临床疗效和可耐受的安全性。然而，库潘尼西在中国患者中的药代动力学、安全性、耐受性和疗效尚未见报道。
这是一项针对中国复发或难治性惰性非霍奇金淋巴瘤（iNHL）患者的库潘尼西单臂、开放标签的I期研究。患者在28天周期的第1、8和15天接受1小时静脉输注60mg库潘尼西，休息1周。在整个研究过程中监测安全性，并测量血浆库潘尼西水平进行药代动力学分析。肿瘤反应由独立的中央放射学审查确定。
16例患者入组，13例接受60mg库潘尼西治疗，中位治疗时间为15.0周。单次静脉输注后，库潘尼西的药代动力学参数与既往研究一致，C为566μg/L，AUC(0-24)为1880μg·h/L，血浆中未观察到蓄积。所有13例患者均报告了治疗中出现的不良事件，最常见的是高血糖（100.0%）、高血压（76.9%）、中性粒细胞计数减少（76.9%）和白细胞计数减少（69.2%）。12例评估患者中有7例达到部分缓解，总缓解率为58.3%。结论：60mg剂量的库潘尼西在中国复发或难治性iNHL患者中耐受性良好，并显示出令人鼓舞的疾病控制效果，因此值得进一步进行临床研究。
NCT03498430（2018年4月13日）。
