Niraparib Demonstrates PFS Benefit in Chinese Population With Advanced Ovarian Cancer

First-line maintenance treatment with the PARP inhibitor niraparib (Zejula) yielded a clinically meaningful and statistically significant improvement in progression-free survival (PFS) vs placebo in Chinese patients with platinum-responsive advanced ovarian cancer, regardless of biomarker status, according to topline data from the phase 3 PRIME trial (NCT03705156) released by Zai Lab Limited.¹

Results showed that the study met its primary end point of PFS and demonstrated a tolerable safety profile in those with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, following a response to platinum-based chemotherapy.

“I believe the data of the PRIME study will have a significant impact on the clinical practice in the first-line treatment of ovarian cancer in China and beyond, as the individualized starting dose regimen has demonstrated an improved safety profile,” Lingying Wu, PhD, director of the Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, said in a press release. “In addition, the PRIME study is the only study conducted in China that has demonstrated that a PARP inhibitor significantly improved PFS when given as monotherapy maintenance therapy in all Chinese patients with newly diagnosed ovarian cancer, regardless of biomarker status.”

The PRIME study enrolled 384 patients with advanced ovarian cancer who achieved a complete response (CR) or partial response (PR) to first-line platinum-based chemotherapy. Patients were randomized 2:1 to receive niraparib or placebo until disease progression. The starting dose of niraparib was individualized at 200 mg except for in patients with a baseline body weight 77 kg or more and a platelet count of 150K/μL or more, in which case the starting dose increased to 300 mg.

The primary end point of the study was PFS as assessed by blinded independent central review. Secondary end points included chemotherapy-free interval, time to first subsequent anti-cancer treatment, and overall survival.²

Niraparib is an oral, once daily PARP inhibitor that has shown promising activity in prior studies in patients with ovarian cancer. In September 2020, the China National Medical Products Administration (NMPA) approved a supplemental new drug application for the agent as a frontline maintenance treatment for adult patients with advanced ovarian cancer who achieved a CR or PR to first-line platinum-based chemotherapy.

Niraparib was also approved as a maintenance treatment for adult patients with high-grade serous epithelial ovarian cancer who achieved a CR or PR to first-line platinum-based chemotherapy by the Hong Kong Department of Health.

Currently, Zai Lab Limited is seeking National Reimbursement Drug List (NRDL) inclusion for niraparib for a first-line ovarian cancer indication. Additionally, the agent is being examined in China in a phase 1b/2 trial (NCT04178460) in combination with tebotelimab for the treatment of patients with advanced gastric cancer, triple-negative breast cancer, biliary tract cancer, and endometrial cancer.³

“The PRIME clinical data in Chinese patients confirmed the clinical profile of niraparib and were consistent with the results seen in the global PRIMA study [NCT02655016],” Alan Sandler, MD, president and head of Global Development, Oncology, Zai Lab, said in a press release. “Importantly, the PRIME study further underscores the status of niraparib as the first and only PARP inhibitor approved globally, including in China, as monotherapy for all-comer patients in the first-line maintenance treatment settings.”

References

1. Zai Lab announces positive topline results from phase 3 PRIME study of ZEJULA (niraparib) as first-line monotherapy maintenance treatment in Chinese women with platinum-responsive advanced ovarian cancer. News release. Zai Lab Limited. November 30, 2021. Accessed November 30, 2021. https://bit.ly/3Ec7esv
2. Clinical trial evaluating the efficacy and safety of ZL-2306 (niraparib) in ovarian cancer patient. clinicaltrials.gov. Updated October 15, 2021. Accessed November 30, 2021. https://clinicaltrials.gov/ct2/show/NCT03705156
3. A study of niraparib combined with MGD013 in patients with advanced or metastatic solid tumor who failed prior treatment. clinicaltrials.gov. Updated April 1, 2021. Accessed November 30, 2021. https://clinicaltrials.gov/ct2/show/NCT04178460