Senaparib Achieves Notable Survival Benefit in Advanced Ovarian Cancer

The investigational PARP inhibitor senaparib (JS109/IMP4297) was found to prolong progression-free survival (PFS) in patients with advanced ovarian cancer, meeting the primary end point of the phase 3 FLAMES study (NCT04169997).¹

Senaparib was designed to selectively bind to PARP 1/2 and prevent PARP-mediated repair of single-strand DNA breaks via the base excision repair pathway. This process may enhance the accumulation of DNA strand breaks while promoting genomic instability eventually leading to apoptosis.

In a press release on findings from the study’s interim analysis, senaparib met the pre-defined efficacy boundary for PFS by independent data monitoring committee. Based on the data, investigators plan to communicate with regulatory authorities on submitting a new drug application for the agent in the future.

“As the first phase 3 clinical study of a domestically developed PARP inhibitor that has achieved positive results for advanced ovarian cancer maintenance treatment following first-line therapy, the FLAMES study’s interim analysis results show that senaparib can significantly extend the PFS of patients with advanced ovarian cancer, regardless of the patient’s [BRCA] mutation status,” Jianjun Zou, MD, president of Global Research and Development at Junshi Biosciences, said in the press release.

Senaparib is an orally available inhibitor of the nuclear enzymes PARP 1/2 that has demonstrated potential antineoplastic activity.² The agent was designed to selectively bind to PARP 1/2 and prevent PARP-mediated repair of single-strand DNA breaks via the base excision repair pathway. This process may enhance the accumulation of DNA strand breaks while promoting genomic instability eventually leading to apoptosis.

Investigators of the randomized, double-blind, placebo-controlled, multi-center phase 3 FLAMES study are evaluating the safety and efficacy of senaparib monotherapy as maintenance treatment following first-line chemotherapy in patients with stage III or IV ovarian cancer who achieved a complete response or partial response. Patients were randomly assigned to receive 100 mg of senaparib or matched placebo once a day.

Secondary end points of the FLAMES study include chemotherapy-free interval, PFS2, time to first subsequent anti-tumor treatment, time from randomization to study treatment discontinuation or death, and overall survival.

Patients [MOU1] 18 years and older with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage III or IV high-grade serous ovarian carcinoma or other histological types of ovarian, fallopian tube, or primary peritoneal cancer harboring BRCA mutations were eligible for enrollment on the trial.

Additional inclusion criteria included completing platinum-based chemotherapy in the first line, having adequate organ and bone marrow function, an ECOG performance status of 0 or 1, and a life expectancy of at least 16 weeks.

Patients with an unclear BRCA mutations status, stage I or II disease, stable disease or progressive disease following first-line chemotherapy, or more than 1 cytoreductive surgery prior to study randomization were unable to enroll on the study.

Patients were also unsuitable for enrollment if they have previously received chemotherapy for any abdominal or pelvic tumor, ascites drawn during the last 2 chemotherapy cycles prior to enrollment, participated in another investigational drug trial during chemotherapy, or have history of other malignancies within the past 5 years.

Receiving any systemic chemotherapy or radiotherapy within 4 weeks of beginning study treatment, having myelodysplastic syndrome or acute myeloid leukemia, active or untreated central nervous system metastases, and receiving prior treatment with a PARP inhibitor were also grounds for exclusion.

References

1. Junshi Biosciences announces phase 3 clinical study of senaparib for advanced ovarian cancer maintenance treatment following first-line therapy met primary endpoint. News release. Junshi Biosciences. April 11, 2023. Accessed April 12, 2023. yhoo.it/410Blyt
2. Senaparib. National Center for Biotechnology Information. Accessed April 12, 2023. bit.ly/3GCRJ07