BeiGene has started enrollment in its Phase 3 clinical trial evaluating the investigational PARP inhibitor pamiparib (BGB-290) as a maintenance therapy for ovarian cancer patients who are responding to platinum-based chemotherapy.
The trial (NCT03519230) is expected to include 216 adult women with confirmed high-grade serous or endometrioid ovarian cancer, including primary peritoneal and fallopian tube cancer, across 15 to 20 sites in China.
Eligible participants must have received at least two prior lines of platinum-based chemotherapy, and achieved a complete or partial response to the last one.
Patients in the trial will be randomly assigned to receive oral pamiparib (60 mg) or a placebo twice a day. Researchers will then examine if pamiparib is better than placebo at preventing or delaying disease progression or death.
Secondary objectives of the trial include overall survival, objective response rate, and duration of response.
“This trial is designed to provide important confirmatory clinical data that could enable registration in the maintenance setting, as well support our planned initial regulatory submission for the treatment of patients with advanced ovarian cancer who carry a germline BRCA1/2 mutation,” Amy Peterson, MD, chief medical officer of immuno-oncology of BeiGene, said in a press release.
Pamiparib is an inhibitor of PARP1 and PARP2 enzymes that has shown promise in laboratory studies, including its ability to cross the blood-brain barrier and to trap PARP enzymes at damaged DNA sites.
By selectively binding to these enzymes, pamiparib prevents key mechanisms of DNA repair, leading to toxic and harmful accumulation of genetic errors in cancer cells that eventually cause them to die.
The candidate is being evaluated in several clinical trials in China, either alone or in combination with checkpoint inhibitors, as a treatment for several solid cancer types.
“In China there are currently no approved PARP inhibitors, despite the multiple approvals of PARP inhibitors in other regions of the world and in a variety of settings. Our development program in ovarian cancer is designed to address the limited treatment options that currently exist for these patients in China,” said Lai Wang, PhD, senior vice president and head of China development at BeiGene.
In an ongoing Phase 1 trial (NCT03333915), out of nine patients with high-grade non-mucinous ovarian cancer enrolled so far, pamiparib treatment induced some sort of benefit in eight patients. Among them, two experienced a partial response, and six had their disease stabilized by the treatment. All patients with BRCA mutations benefited from pamiparib. The trial is still enrolling up to 85 participants in China.
Data from the trial was recently presented in the poster, “A phase I dose escalation study of BGB-290 in Chinese subjects with advanced ovarian, fallopian, and primary peritoneal, or advanced triple-negative breast cancer,” at the American Association for Cancer Research 2018 Annual Meeting held in April in Chicago.
“As we look to improve the current 30 to 40 percent five-year survival rate for patients with advanced ovarian cancer, I look forward to evaluating pamiparib as a potential new maintenance therapy,” said Ding Ma, MD, professor and chairman of the department of obstetrics and gynecology at Tongji Medical College of Huazhong University of Science and Technology and principal investigator of the trial.