Abstract 3891: A phase 1 study to evaluate the pharmacokinetics (PK) and safety of niraparib in Chinese patients with epithelial ovarian cancer (OC)

Abstract

Abstract Purposes: To characterize the PK and safety of niraparib as a maintenance therapy in Chinese OC patients. Methods: Eligible patients were randomized 1:1:1 to 100, 200, or 300 mg once daily cohort. Plasma samples were collected following single and multiple dosing and analyzed using a validated LC/MS/MS method. PK parameters were analyzed by standard non-compartmental approach with WinNonlin. A population PK (Pop PK) model was derived from pooled PK data of current study and two previous PK studies in Caucasian: the dose escalation and expansion study (PN001), and the ENGOT-OV16/NOVA sub-study. Non-linear mixed effect modeling was done with NONEM®. Results: 36 patients were randomized and included in the PK and safety analysis set. Niraparib was rapidly absorbed after dosing with tmax~3h. The exposure of niraparib was dose proportional, while other PK parameters such as t1/2, accumulation ratio were dose independent (Table 1). The POP-PK analysis model was established using PK data from 144 Caucasians and 39 Chinese. Chinese patients had a slightly higher Cmax than Caucasian patients but similar total exposure (AUC0-∞) after a single dose. Simulation by final Pop PK model indicated comparable total exposure (AUC0-∞) and Cmax between Chinese and Caucasian patients at the steady-state following multiple daily doses. Treatment emergent AEs (TEAEs) occurred in 97.2% of all patients treated with niraparib. The most frequent (>20%) TEAEs were consistent with the known safety profile of PARP inhibitors. TEAEs of Grade 3/4 reported in ≥ 5% patients included decreased platelet count (13.9%), decreased neutrophil count (11.1%), anemia (8.3%) and increased gamma-glutamyl transferase (5.6%). Conclusions: The PK profile of niraparib in Chinese was consistent with its known profile in Caucasian. Niraparib in Chinese OC patients has a manageable safety profile, similar to that observed in global studies. (NCT03551171) Citation Format: Jian Zhang, Yu Nong Gao, Ge Lou, Ru Tie Yin, Jian Mei Hou, James Yan, Jing Li, Zhi Yi Zhang, Xiao Hua Wu. A phase 1 study to evaluate the pharmacokinetics (PK) and safety of niraparib in Chinese patients with epithelial ovarian cancer (OC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3891.