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

Abstract

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 60mg infusion of copanlisib over 1h on days 1, 8, and 15 of a 28-day cycle, with 1week 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 60mg of copanlisib for a median of 15.0weeks. With a Cmax of 566μg/L and a AUC (0-24) of 1880μg·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 60mg and demonstrated encouraging disease control, thus warranting further clinical investigation. NCT03498430 (April 13, 2018).