A phase I pharmacokinetic study of copanlisib in Chinese patients with relapsed indolent non-Hodgkin lymphoma

• Published in: Cancer chemotherapy and pharmacology 2022-06, Vol.89 (6), p.825-831
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Cancer Research; China; Clinical Trial Report; Disease control; Humans; Hyperglycemia; Hypertension; Intravenous administration; Intravenous infusion; Leukocytes (neutrophilic); Lymphoma; Lymphoma, Non-Hodgkin - drug therapy; Medicine; Medicine & Public Health; Non-Hodgkin's lymphoma; Oncology; Patients; Pharmacokinetics; Pharmacology; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases; Pyrimidines; Quinazolines; Safety; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-022-04417-3

Purpose 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. Methods 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. Results Sixteen patients were enrolled and 13 were treated with 60 mg of copanlisib for a median of 15.0 weeks. With a C max 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. Clinical trial registration number NCT03498430 (April 13, 2018).