260P - A phase I study of copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor, in Chinese patients with relapsed indolent non-Hodgkin lymphoma (iNHL)

Background

Copanlisib is a novel, potent, i.v. pan-PI3K inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms that has demonstrated robust anti-tumor efficacy in patients with iNHL and was approved by the FDA in September 2017. Here we report on the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent copanlisib in Chinese patients with relapsed iNHL (NCT03498430).

Methods

Patients with relapsed histologically confirmed iNHL received copanlisib 60 mg as a 1-h i.v. infusion on days 1, 8, and 15 of a 28-day cycle. Safety was monitored throughout the study. The efficacy variable was objective tumor response rate (ORR) per independent radiologic review (Cheson et al. J Clin Oncol 2007). Plasma copanlisib levels were measured for pharmacokinetic analysis.

Results

13 patients (11 with follicular lymphoma and 2 with marginal zone lymphoma) received treatment; 12 patients were evaluable for efficacy. Median age was 40 years (range 30-64). The most common treatment-emergent adverse events of worst grade 3 were transient hypertension in 7 patients (53.8%) and hyperglycemia in 6 patients (46.2%), with no grade 4 hyperglycemia or hypertension events. No grade 5 events were reported. Copanlisib PK exposures (maximum observed concentration and area under the concentration vs time curve after single-dose administration) were in range of those from previous studies of copanlisib in non-Chinese patients. The ORR was 50% (95% CI 21.1, 78.9), with 6 patients achieving a partial response and 6 patients with stable disease as best response. The disease control rate was 100% (95% CI 73.5, 100.0). The estimated median duration of response was to be 63 days (range 1-115, including censored values). The median duration of stable disease was 163 days (range 106-218, including censored values).

Conclusions

Copanlisib was well tolerated in Chinese patients with relapsed iNHL at the approved clinical dose of 60 mg, with PK profiles comparable to non-Chinese patients. The observed efficacy profile of copanlisib was in the range of overall response rates previously observed for copanlisib monotherapy.

Clinical trial identification

NCT03498430.

Editorial acknowledgement

Jack Adams, Complete HealthVizion, McCann Health Medical Communications.

Legal entity responsible for the study

Bayer HealthCare Co. Ltd.

Funding

Bayer HealthCare Co. Ltd.

Disclosure

Y. Niu, T. Li, J. Zhai: Full/Part-time employment: Bayer HealthCare Co. Ltd. G. Cisternas, F. Hiemeyer, S. Reschke: Full/Part-time employment: Bayer AG. F. Huang, J. Garcia-Vargas, B.H. Childs, A. Mehra, C. Granvil: Full/Part-time employment: Bayer HealthCare Pharmaceuthicals, Inc. All other authors have declared no conflicts of interest.