Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumours, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III–IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years. The primary endpoint was progression-free survival assessed by a blinded independent central review. At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32–0.58; P < 0.0001). The benefit of senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively.
Senaparib is a novel and potent PARP1 inhibitor with a unique chemical structure and high inhibitory activity. Research has found that Senaparib not only effectively inhibits the enzymatic activity of PARP1 and PARP2 but also induces the "trapping" of PARP1 on DNA, leading to the stalling of DNA replication forks and double-strand DNA breaks, ultimately causing cell death. This "trapping" effect is considered a key factor in the therapeutic efficacy of PARP1 inhibitors.
