First-line Senaparib Maintenance Meets PFS End Point in Advanced Ovarian Cancer

Maintenance therapy with senaparib (IMP4297) improved progression-free survival (PFS) vs placebo for patients with stage III/IV ovarian carcinoma, fallopian tube cancer, or primary peritoneal cancer who achieved a complete or partial response to first-line platinum-based chemotherapy, meeting the primary end point of the phase 3 FLAMES trial (NCT04169997).¹

An independent data monitoring committee (IDMC) concluded that the primary end point met the predefined efficacy boundary at the trial’s prespecified interim analysis. Junshi Biosciences and IMPACT Therapeutics plan to communicate with regulatory authorities regarding a new drug application for senaparib.

“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 breast cancer susceptibility gene [BRCA] mutation status,” Jianjun Zou, MD, PhD, president of Global Research and Development at Junshi Biosciences, stated in a news release. “We will collaborate with our partner IMPACT Therapeutics to engage in communication with regulatory agencies and look forward to expanding our commercial cancer drug portfolio to provide more effective treatment options at a lower cost for patients with advanced ovarian cancer.”

Senaparib is a novel PARP inhibitor, and in August 2022, the FDA granted an orphan drug designation to the fixed-dose combination capsule of senaparib and temozolomide for the treatment of adult patients with small cell lung cancer.²

FLAMES is a randomized, double-blind, placebo-controlled, multicenter phase 3 study evaluating the efficacy and safety of senaparib monotherapy as maintenance treatment in patients with advanced ovarian cancer who responded to first-line platinum-based chemotherapy.¹

Patients were required to be at least 18 years of age with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade serous ovarian cancer or other histological types of ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a BRCA mutation, per local pathological diagnosis.³

Other key inclusion criteria included normal organ and bone marrow function, an ECOG performance status of 0 or 1, and a life expectancy of at least 16 weeks. Patients with CA125 levels no higher than the upper limit of normal (ULN) were permitted to enroll. Those who had CA125 levels above the ULN were allowed to take a second test at least 7 days after the first; however, if the second CA125 assessment was at least 15% higher than the first, they were not permitted to enroll.

Patients were excluded from the trial if they had an unclear BRCA mutation status, had early-stage disease (FIGO stage I/II), had stable disease or progressive disease following first-line chemotherapy, underwent more than 1 cytoreductive surgery prior to randomization, or previously received chemotherapy for any abdominal or pelvic tumor. Any systemic chemotherapy or radiotherapy was not allowed within 4 weeks of study treatment, except for palliative reasons.

Patients who completed and responded to first-line platinum-based chemotherapy with carboplatin or cisplatin were randomly assigned to receive oral senaparib at a starting dose of 100 mg, or matching placebo.

Along with the primary end point of PFS per blinded independent central review, secondary end points consisted of chemotherapy-free interval, time to second progression (PFS2), time to subsequent treatment, time to treatment discontinuation or death, and overall survival.

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. https://www.junshipharma.com/en/
2. FDA granted orphan drug designation to IMP4297+TMZ for SCLC. News release. IMPACT Therapeutics. August 11, 2022. Accessed April 12, 2023. http://www.impacttherapeutics.com/en/new/161.html
3. A study of IMP4297 as maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer (FLAMES). ClinicalTrials.gov. Updated February 12, 2020. Accessed April 12, 2023. https://clinicaltrials.gov/ct2/show/NCT04169997