GSK's phase III FIRST-ENGOT-OV44 trial evaluating the combination of Jemperli (dostarlimab) and Zejula (niraparib) in first-line advanced ovarian cancer has met its primary endpoint of progression-free survival (PFS). The study, sponsored by GSK and led by GINECO, demonstrated a statistically significant improvement in PFS with the addition of dostarlimab to standard-of-care carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab.
The trial's design included patients with stage III or IV nonmucinous epithelial ovarian cancer. Participants were initially randomized into three arms: standard chemotherapy followed by placebo, standard chemotherapy followed by niraparib, and standard chemotherapy plus dostarlimab followed by niraparib and dostarlimab. Due to the approval of PARP inhibitors in the first-line setting, the placebo arm was closed, and patients were subsequently randomized to the niraparib or combination arms.
Overall Survival Data Awaited
While the primary endpoint was met, the key secondary endpoint of overall survival (OS) did not reach statistical significance. Further analyses are ongoing, and the data will be shared with health authorities and presented at an upcoming scientific meeting. According to Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, the company will continue to evaluate the potential of this combination in gynecological cancers.
The safety and tolerability profile of the combination was generally consistent with the known profiles of the individual agents.
Ovarian Cancer Context
Ovarian cancer is the eighth most common cancer in women worldwide. Despite high initial response rates to platinum-based chemotherapy, approximately 85% of patients experience disease recurrence. Once recurrence occurs, the disease is rarely curable, with decreasing time intervals between subsequent recurrences.
About Jemperli and Zejula
Jemperli (dostarlimab) is a programmed death receptor-1 (PD-1)-blocking antibody and serves as the backbone of GSK's immuno-oncology research and development program. Zejula (niraparib) is an oral, once-daily Poly (ADP-ribose) polymerase (PARP) inhibitor. Jemperli is currently indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer in the US. Zejula is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.
