Zejula Maintenance Therapy Extends Progression-free Survival in Advanced Ovarian Cancer Patients, Phase 3 Trial Shows

Maintenance treatment with Zejula (niraparib) extended the time without disease worsening in women with advanced ovarian cancer who had responded to first-line chemotherapy, according to updated results of a Phase 3 trial.

The study, called PRIMA (NCT02655016), is a randomized, double-blind clinical trial assessing Zejula as a maintenance therapy in 620 women with newly diagnosed ovarian cancer following response to platinum-based chemotherapy.

All patients have stage III or IV cancer, meaning it has spread outside the ovaries to the nearby lymph nodes or to other regions in the body. Chemotherapy was given before or after surgery to remove the tumor.

Zejula’s starting dose is 200 mg once-daily in patients with baseline weight under 77 kg or a platelet count below 150K/μL, and 300 mg in all other participants. Each treatment cycle lasts 28 days.

Besides providing prolonged time without disease progression, or progression-free survival, regardless of the patients’ biomarker status, the results showed that treatment with Zejula was consistent with previous clinical trials in its safety and tolerability. Full results from PRIMA will be presented at an upcoming scientific meeting.

Zejula is an oral PARP inhibitor. It is marketed by GlaxoSmithKline (GSK) and its subsidiary Tesaro, and works by blocking the activity of PARP proteins, which are enzymes involved in DNA repair inside cells.

“Almost 300,000 women around the world are diagnosed with ovarian cancer every year, yet only about 15% of patients are currently eligible to receive PARP inhibitors as their initial therapy,” Hal Barron, GSK’s chief scientific officer, and president of research and development, said in a press release. “These exciting data demonstrate that Zejula has the potential to significantly benefit even more women.”

Zejula is currently approved in the U.S. and Europe as a maintenance therapy for women with recurrent and high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have at least partially responded to platinum-based chemotherapy.

Recently, the U.S. Food and Drug Administration granted priority review to Tesaro’s application seeking to extend the approval of Zejula for women with late-stage ovarian cancer, previously treated with three or more chemotherapies, and with a BRCA mutation or a mutation in other DNA repair genes. The submission was based on results of the QUADRA Phase 2 study (NCT02354586), which showed that Zejula had relevant anti-cancer activity across different subgroups.

Another Phase 3 trial, called BRAVO (NCT01905592) is evaluating Zejula in patients with metastatic breast cancer and germline mutations in BRCA.

The therapy is also being tested as a combination approach. The TOPACIO Phase 1/2 trial (NCT02657889) showed that a combination of Zejula with Keytruda (pembrolizumab, by Merck) was well-tolerated and has promising anti-tumor activity in patients with advanced, platinum-resistant ovarian cancer.

In addition, the ENGOT-OV24/AVANOVA study (NCT02354131), also a Phase 1/2 trial, is evaluating Zejula with Avastin (bevacizumab, by Genentech) in women with recurrent, platinum-sensitive ovarian cancer.