Senaparib Receives NMPA Approval As First-Line Maintenance in Ovarian Cancer

China’s National Medical Products Administration (NMPA) has approved senaparib (IMP4297) monotherapy for the maintenance treatment of adult patients with advanced epithelial high-grade ovarian, fallopian tube, or primary peritoneal cancer who achieved a complete or partial response after the completion of first-line platinum-based chemotherapy.1

Senaparib is a potent and selective PARP1/2 inhibitor with a novel molecular structure that enables high in vitro and in vivo activity and a favorable safety profile.

Findings from the phase 3 FLAMES trial (NCT04169997) supported this regulatory decision. Topline results from FLAMES were first presented during the 2023 ESMO Congress and subsequently published in Nature Medicine on May 15, 2024. At a median follow-up of 22 months, single-agent senaparib significantly reduced the risk of progression or death by 57% in patients with newly diagnosed advanced ovarian cancer regardless of BRCA mutation status (HR, 0.43; 95% CI, 0.32-0.58; P < .0001).1,2 The median progression-free survival (PFS) by blinded independent central review (BICR) assessment per RECIST 1.1 criteria was not reached (NR) in the senaparib arm vs 13.6 months in the placebo arm.2

Among patients harboring BRCA mutations, the median PFS was NR with senaparib vs 15.6 months with placebo (HR, 0.43; 95% CI, 0.24-0.76; P = .0026). For those with BRCA-negative disease, these respective figures were NR vs 12.9 months (HR, 0.43; 95% CI, 0.30-0.61; P < .0001).

Senaparib exhibited a tolerable safety profile, and no new safety signals were identified.1 Moreover, senaparib showed a more favorable non-hematological safety profile compared with other PARP inhibitors.2 Grade 3 or higher treatment-emergent adverse effects (AEs) were reported in 66.3% and 20.3% of patients in the senaparib and placebo groups, respectively.3 AEs leading to dose reduction occurred in 63.3 % vs 6.0% of patients; there were no toxicities leading to death.

Notably, both homologous recombination deficiency (HRD)–positive and HRD-negative patient populations benefited from senaparib maintenance therapy.1 IMPACT Therapeutics, the drug’s developer, asserts that these findings support the use of senaparib as a standard of care for first-line maintenance therapy in patients with newly diagnosed ovarian cancer.

"It is our great pleasure to share with you the successful approval of senaparib for the Chinese market, which is another strong proof of the excellence of IMPACT's in-house synthetic lethality research and development platform and the research and development execution team,” “Sui Xiong Cai, PhD, chief executive officer of IMPACT Therapeutics, stated in a news release.

The randomized, double-blind, placebo-controlled, multicenter, FLAMES study evaluated the efficacy and safety of senaparib as monotherapy for maintenance treatment in patients at least 18 years of age with newly diagnosed, FIGO stage III/IV, high-grade serous or endometrioid ovarian cancer who had completed first-line chemotherapy and achieved a response.2 An ECOG performance status of 0 or 1 was also required.4

A total of 404 patients were enrolled onto the study and randomly assigned 2:1 to receive a starting 100 mg dose of senaparib (n = 270) or placebo (n = 133) in tablet form each day.2,4

The primary end point was PFS by BICR assessment, with key secondary end points including chemotherapy-free interval, investigator-assessed time to second progression, time to first subsequent anti-tumor treatment, time from randomization to discontinuation or death, overall survival, and safety.

References

1. Senaparib approved by NMPA for 1L maintenance therapy in ovarian cancer. News Release. IMPACT Therapeutics. January 17, 2024. Accessed January 17, 2025. http://www.impacttherapeutics.com/en/new/184.html
2. IMPACT Therapeutics presented pivotal phase 3 clinical data for senaparib as first-line maintenance therapy in advanced ovarian cancer patients at ESMO Congress 2023 as a proffered late-breaking paper presentation. News Release. IMPACT Therapeutics. October 20, 2023. Accessed January 17, 2025. http://www.impacttherapeutics.com/en/new/174.html
3. Wu X, Liu J, Wang X, et al. Efficacy and safety of senaparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer (FLAMES): a randomized, double-blind, placebo-controlled, phase 3 trial. Ann Oncol. 2023;34(suppl 2):LBA36. doi:10.1016/iotech/iotech100589
4. A study of IMP4297 as maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer (FLAMES). ClinicalTrials.gov. Updated February 2, 2020. Accessed January 17, 2025.https://clinicaltrials.gov/study/NCT04169997