Treatment with dostarlimab plus chemotherapy demonstrated a statistically significant improvement in progression-free survival compared with placebo and chemotherapy among patients with advanced or recurrent endometrial cancer.
Findings from part 1 of the phase 3 RUBY trial (NCT03981796) demonstrated that dostarlimab-gxly (Jemperli) plus standard-of-care chemotherapy use in adults with primary advanced or recurrent endometrial cancer met its primary end point of progression-free survival (PFS) vs placebo plus chemotherapy, according to a press release from the manufacturer.
Regulatory submissions based on trial data are planned for the first half of 2023, and full results will be published in a medical journal and shared at a future scientific meeting.
Dostarlimab yielded a statistically significant and clinically meaningful PFS benefit in the overall patient population and among patients in the mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) subgroup. Trial investigators also reported a clinically relevant PFS benefit in the mismatch repair proficient (MMRp) or microsatellite stable (MSS) patient subgroup. Additionally, a favorable trend in terms of overall survival was observed among the overall population and both the dMMR/MSI-H and MMRp/MSS subgroups, although the data were immature at the time of the analysis.
Dostarlimab produced a safety profile that was consistent with those previously reported in clinical trials. The most common treatment-emergent adverse effects (TEAEs) observed in patients receiving dostarlimab with chemotherapy included nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, and diarrhea.
“Based on these positive headline results from the RUBY phase 3 trial, GSK intends to seek regulatory approvals for a potential new indication for dostarlimab-gxly in the treatment of primary advanced or recurrent endometrial cancer,” Hesham Abdullah, senior vice president and global head of Oncology Development at GSK, said in the press release.
Investigators of the global, randomized, double-blind, multicenter phase 3 RUBY/ENGOT-EN5/GOG3031/NSGO trial enrolled patients with primary advanced or recurrent endometrial cancer across 2 parts. Part 1 of the trial assessed dostarlimab plus carboplatin-paclitaxel followed by dostarlimab compared with carboplatin-paclitaxel plus placebo followed by placebo. The second part of the trial will evaluate dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib (Zejula) vs the same placebo arm included in part 1.
The RUBY trial is part of an international collaboration between the European Network of Gynecological Oncological Trial groups and the Gynecologic Oncology Group Foundation.
Secondary end points for parts 1 and 2 of the trial included PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability of treatment.
Patients 18 years and older with histologically or cytologically proven endometrial cancer with recurrent or advanced disease were eligible to enroll on the trial. Additional inclusion criteria included having primary stage III or IV disease or first recurrent endometrial cancer, an ECOG performance status of 0 or 1, and adequate organ function.
Patients were unable to enroll on the study if they had already received adjuvant systemic therapy for primary stage III or IV disease. Patients were also unsuitable for enrollment if they had more than 1 recurrence of endometrial cancer, received prior therapy with an anti–PD-L1 agent, received prior anti-cancer therapy within 21 days prior to study treatment, had known uncontrolled central nervous system metastases, or have not recovered adequately from AEs from any major surgery before starting treatment therapy.
Jemperli (dostarlimab-gxly) RUBY phase III trial met its primary endpoint in a planned interim analysis in patients with primary advanced or recurrent endometrial cancer. News release. GSK plc. December 2, 2022. Accessed December 5, 2022. bit.ly/3B9JUw0