A phase III CHIPRO study of chiauranib plus weekly paclitaxel for platinum-resistant or refractory ovarian cancer.

Abstract

LBA5504 Background: Platinum-resistant or refractory ovarian cancer is associated with poor prognosis and has limited treatment options. Chiauranib (Ibcasertib) is an oral, novel small-molecule multi- kinase inhibitor that targets tumor cell proliferation, neoangiogenesis, and immunosuppressive tumor microenvironment through inhibition of Aurora B, VEGFR1/2, PDGFRα/β, and CSF-1R. Prior studies suggested clinical activity with chiauranib in combination with etoposide or weekly paclitaxel in this setting. Methods: We conducted a randomized, double-blind, placebo-controlled, multicenter phase III trial (CHIPRO) to evaluate the efficacy and safety of chiauranib plus weekly paclitaxel in patients with platinum-resistant or refractory ovarian cancer. Patients were randomized 1:1 to receive weekly paclitaxel plus either chiauranib (CP group) or placebo (PP group). Randomization was stratified by prior lines of chemotherapy (1-2 vs ≥3) and platinum-free interval (≥6 months vs <6 months). Patients received up to six cycles of combination therapy followed by maintenance chiauranib or placebo in those without progression. Dual primary endpoints were progression-free survival (PFS) per blinded independent review committee according to RECIST v1.1 and overall survival (OS). The study was designed to demonstrate superiority of the experimental regimen in either endpoint. Results: Between December 20, 2021, and July 29, 2025, 459 patients were enrolled; 70% had received prior anti-angiogenic therapy. At the data cutoff (July 29, 2025), the median follow-up was 16.0 months (95% CI, 14.3–17.7). Median PFS was 4.57 months (95% CI, 4.14–5.52) in the CP group versus 2.69 months (95% CI, 1.58–2.76) in the PP group (HR, 0.427; 95% CI, 0.34–0.54; P < 0.001), representing a 57% reduction in progression risk. PFS benefit was observed with CP regardless of prior anti-angiogenic exposure. Median OS was 12.09 months (95% CI, 10.51–15.18) in the CP group and 12.12 months (95% CI, 10.25–13.31) in the PP group (HR, 0.932; 95% CI, 0.73–1.20; P=0.583). A statistically significant OS benefit was observed in patients who did not receive subsequent anticancer therapy (HR, 0.599; 95% CI, 0.39–0.91; P = 0.016). Favorable OS trends were also noted in subgroups previously treated with PARP inhibitors and in those received subsequent platinum-based chemotherapy. The most common grade ≥3 treatment-emergent adverse events in the CP group were leukopenia, neutropenia and anemia. Safety was consistent with prior experience, and no new safety signals were identified. Conclusion: Chiauranib plus weekly paclitaxel significantly prolonged PFS in patients with platinum-resistant or refractory ovarian cancer, with a manageable and predictable safety profile. Significant benefit was also observed in the subgroup previously treated with anti-angiogenic agents, supporting this regimen as a promising new treatment option. Clinical trial information: NCT04921527 .