Abstract
BACKGROUND: Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction. METHODS: A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1. RESULTS: From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8-NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8-5·6) and 5·6 months (95% CI 3·4-7·0), respectively. CONCLUSIONS: This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib).