Zejula (niraparib) showed an ability to treat people with recurrent and heavily treated ovarian cancer, particularly those with mutations in DNA repairing genes, results of a Phase 2 trial show.
Tesaro’s Zejula is an orally active PARP inhibitor, a class of drugs used for treating cancer in some women who have mutations in BRCA genes. The treatment relies on the notion that cancers with BRCA mutations use other enzymes, like PARP, to repair their DNA. Inhibiting, or blocking, these ‘backup’ enzymes leads to an accumulation of mutations that is not sustainable, eventually killing cancer cells.
While PARP inhibitors works best in BRCA-mutated cancers, there is scientific evidence that some cancers without BRCA mutations may also respond to this type of therapy. Tesaro is evaluating Zejula as a treatment of advanced ovarian and breast cancer in patients with and without BRCA mutations.
The treatment is approved in the U.S. and Europe, as a maintenance therapy for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have shown a complete or partial response to platinum-based chemotherapy.
Tesaro conducted this Phase 2 trial, called QUADRA (NCT02354586), to evaluate Zejula’s efficacy and safety as single treatment for patients with epithelial ovarian cancer who have gone through three or four prior chemotherapy regimens.
One of trial’s aims is to test this drug in patients that do not carry BRCA mutations.
QUADRA, an open-label, single arm study, enrolled 461 patients, who received a starting dose of 300 milligrams of Zejula once a day in a cycle of 28 days.
Clinical benefit was assessed by monitoring changes in the patients’ quality of life, response to treatment, tumor growth, and adverse events.
Most patients, 92%, had no previous treatment with a PARP inhibitor, and among them, a minority — 15% — carried BRCA mutations. Most were also resistant to platinum-based chemotherapy, and 63 percent had been treated earlier with bevacizumab (brand names, Avastin or Mvasi), an approved chemotherapy for platinum-resistant, recurrent ovarian cancer.
Zejula led to positive outcomes as an at least a fourth-line treatment in 55 patients with BRCA mutations. Among this group, tumor burden was reduced in 31% of patients, with a median response duration of 9.4 months.
Patients with four or five prior treatments, and who had responded to platinum drugs (45 people) also had a positive response to treatment. These patients did not carry BRCA mutations, but were positive for mutations in homologous recombination genes, which are also involved in DNA repair. An overall response rate — a measure of tumor growth — was reduced in 29% of patients, and such response lasted for a median of 9.2 months.
Most common adverse events were as expected from earlier clinical observations, and included myelosuppression, or reduced bone marrow activity that causes fewer blood cell production. This effect was managed by adjusting the doses of Zejula.
Based on these results, Tesaro may request that Zejula’s label be expanded. The company is preparing to meet with the U.S. Food and Drug Administration (FDA) to discuss a supplement New Drug Application covering patients with these cancers.
“These results demonstrated that Zejula is active as a late-line treatment for patients beyond those with BRCA mutations, which is the only treatment setting in which PARP inhibitors are approved today,” Mary Lynne Hedley, president and chief operating officer of Tesaro, said in a news release.
“In addition, the QUADRA data describe Zejula monotherapy activity in platinum-resistant/refractory patients, providing important context for our TOPACIO study of Zejula in combination with an anti-PD-1 inhibitor,” Hedley added.
TOPACIO is a Phase 2 trial (NCT02657889) testing Zejula and Keytruda (pembrolizumab) in patients with platinum-resistant ovarian cancer or triple negative breast cancer. Keytruda is an anti-PD-1 antibody that boosts the immune response against cancer cells. TOPACIO is expected to conclude in February.
Other clinical trials of this treatment in ovarian cancer patients are also underway; a full list is available here.