1000P - Efficacy and safety of oral poly (ADP-ribose) polymerase inhibitor fluzoparib in patients with BRCA1/2 mutations and platinum sensitive recurrent ovarian cancer

Abstract

BackgroundFluzoparib is a potent orally administered poly(ADP-ribose) polymerase (PARP) inhibitor. The safety and tolerability of fluzoparib has been evaluated in a phase 1 trial (NCT02575651). In this study, we aim to characterize the efficacy and safety of fluzoparib in patients (pts) with germline BRCA1/2 mutations and platinum sensitive recurrent ovarian cancer who had received ≥2 prior lines of chemotherapy. MethodsThis was an open-label, multi-centre, phase 2 study of oral fluzoparib in pts with recurrent ovarian cancer. Adult pts (≥18 years) with germline BRCA1 or BRCA2 mutations and platinum-sensitive recurrent high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with two or more previous platinum-based chemotherapy regimens were enrolled. Patients were treated with fluzoparib capsule at 150mg orally twice daily up to disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. ResultsFrom April 4 2018 to March 21 2019, 113 pts at Chinese national-wide 26 sites were received the fluzoparib. At the data cutoff date (April 15, 2019), 103 pts were efficacy evaluable (follow-up ≥8 weeks). The ORR and disease control rate (DCR) were 64.1% (66/103) and 95.1% (98/103), respectively. Complete response (CR) was observed in 9 pts (8.7%). Median duration of response (DOR) and progression free survival (PFS) have not yet been reached. Any grade treatment-related AEs (TRAEs) occurred in 108 patients (95.6%). The most common (≥20%) TRAE were nausea (55.8%), fatigue (47.8%), white blood cell count decreased (44.2%), anemia or decreased hemoglobin (42.5%), neutrophil count decreased (31.9%), decreased appetite (30.1%), thrombocytopenia (29.1%), and vomiting (23.9%). The most common grade ≥3 TRAE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption and dose reduction in 31.0% and 21.1% of patients, respectively. ConclusionsFluzoparib demonstrated promising antitumor activity and acceptable safety in patients with advanced BRCA1/2-mutated ovarian cancer. And this is the first report of a PARP inhibitor in Chinese patients with BRCA1/2 mutations and recurrent ovarian cancer. Clinical trial identificationNCT03509636. Legal entity responsible for the studyJiangsu Hengrui Medicine Co. LTD, China. FundingJiangsu Hengrui Medicine Co. LTD. DisclosureJ. Zou: Shareholder / Stockholder / Stock options: Jiangsu Hengrui Medicine Co. LTD. Q. wang: Shareholder / Stockholder / Stock options: Jiangsu Hengrui Medicine Co. LTD. All other authors have declared no conflicts of interest.