1004P - A prospective evaluation of tolerability of niraparib dosing based on baseline body weight (BW) and platelet (plt) count: Blinded pooled interim safety data from the NORA study

Abstract

BackgroundNiraparib is a highly selective PARP-1/-2 inhibitor approved by FDA for the maintenance therapy of platinum-sensitive recurrent (PSR) ovarian cancer based on the significantly improved progression-free survival for niraparib-treated patients (pts) in the phase III NOVA study. A retrospective analysis of NOVA study suggests that pts with BW <77kg or baseline plt count <150*109/L may have an improved safety profile from a starting dose of 200mg once daily (QD) without compromising efficacy. A double-blinded, 2:1 randomized, placebo-controlled phase III study (NORA) is being conducted in China to investigate niraparib as maintenance therapy in Chinese pts with PSR ovarian cancer. The dosing regimen in the study was 300mg QD but the study protocol was subsequently amended to have a starting dose of either 300 or 200mg of niraparib/placebo QD based on baseline BW and plt counts. The trial has completed accrual and remains blinded for efficacy and safety. The current analysis was intended to evaluate niraparib tolerability for pts starting treatment with an individualized starting dose and compare with that in pts with the fixed starting dose of 300mg QD. MethodsThe initial protocol adopted a fixed starting dose of 300mg QD. After 16 patients were enrolled, the protocol was amended to start niraparib treatment at a dose of 200mg QD in pts with BW <77kg or plt count <150*109/L, and 300mg for others. Blinded data were pooled from niraparib and placebo arms. ResultsA total of 265 pts had been enrolled, and 232 pts who have been followed up≥90 days ending Mar 31, 2019 were included in this analysis. There were no major differences in key pts demographics or disease characteristics between both arms. Key safety data are presented in the table. More detailed safety data in all population will be disclosed. ConclusionsThe results indicate that niraparib tolerability will be improved with a starting dose based on body weight or platelet count. Clinical trial identificationNCT03705156. Editorial acknowledgementJun Wan and John Zhang of Zai Lab Writing and coordinated by Sean Li and Wendy Zhang of Zai Lab, Inc, funded by Zai Lab, Inc. (Shanghai,China). Legal entity responsible for the studyZai Lab (Shanghai) Co., Ltd. FundingZai Lab (Shanghai) Co., Ltd. DisclosureJ. Hou: Full / Part-time employment: Zai Lab (Shanghai) Co., Ltd C. Zhang: Full / Part-time employment: Zai Lab (Shanghai) Co., Ltd Y. Hei: Full / Part-time employment: Zai Lab (Shanghai) Co., Ltd. All other authors have declared no conflicts of interest.Table: 1004PTable: 1004PPre-Amendment, Fixed starting dose (pooled niraparib and placebo arms)Post-Amendment, Individualized starting dose (pooled niraparib and placebo arms )300mg (N=16)300mg (N=14)200mg (N=202)Total (N=216)Median BW, kg (min, max)62 (40,76)83 (78,94)59 (37,82)61 (37,94)Median plt count,109/L (min, max)211 (124,336)187(153,325)184 (62,447)184 (62,447)Any ≥ grade 3 TEAE, n(%)9 (56.3)4 (28.6)56 (27.7)60 (27.8)≥Grade 3 thrombocytopenia, n(%)3 (13.8)1 (7.1)6 (3.0)7 (3.2)≥Grade 3 anemia, n(%)4 (25.0)2 (14.3)9 (4.5)11 (5.1)≥Grade 3 neutropenia, n(%)2 (12.5)025 (12.4)25 (11.6)Any serious TEAE, n(%)4 (25.0)1 (7.1)19 (9.4)20 (9.3)TEAE leading to end of treatment, n (%)1 (6.3)03 (1.5)3 (1.4)