Following the positive phase 3 results, GSK anticipates regulatory submissions in the first half of 2023.
Dostarlimab (Jemperli; GSK) plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by dostarlimab showed a statistically significant and clinically meaningful improvement in adult patients with primary advanced or recurrent endometrial cancer, according to the interim analysis results from part 1 of a 2-part study looking at immune-oncology therapy/standard-of-care chemotherapy combination.
The treatment met the primary endpoint of investigator-assessed progression-free survival (PFS) in 2 prespecified subgroups—those with mismatch repair proficient (MMRp)/ microsatellite stable (MSS) and those with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H).
“Patients with primary advanced or recurrent endometrial cancer have limited treatment options,” said Hesham Abdullah, senior vice president, global head of Oncology Development, GSK, in a press release. “Long-term outcomes remain poor, and new treatment options are urgently needed to evolve the current standard of care, which is platinum-based chemotherapy.”
Dostarlimab plus standard-of-care chemotherapy followed by dostarlimab also showed a possible association with overall survival (OS) in both subgroups. There are not enough mature OS data to make an official association.
Endometrial cancer, which affects the endometrium, is the most common gynecologic cancer in the United States. It is also the second most common gynecological cancer worldwide. As many as 1 in 5 cases are diagnosed in the advanced stage, when treatment becomes increasingly difficult.
Researchers conducted the 2-part global, randomized, double-blind, multicenter phase 3 RUBY trial to evaluate the efficacy and safety of dostarlimab combination therapy for patients with primary advanced or recurrent endometrial cancer.
Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab against carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating the safety and efficacy of dostarlimab with carboplatin-paclitaxel followed by dostarlimab plus niraparib against carboplatin-paclitaxel and placebo followed by placebo.
Among subgroup populations, the endometrial cancer patients in the dMMR/ MSI-H group expressed statistically significant and clinically meaningfully benefits from the dostarlimab combination therapy. Dostarlimab combination observably benefited the overall patient population as well. Further, the data suggested that patients in the MMRp/ MSS subgroup experienced clinically relevant benefits in PFS, according to the investigators.
RUBY is the only first-line trial for an immune-oncology therapy/standard-of-care chemotherapy combination to improve PFS in patients with primary advanced or recurrent endometrial cancer.
Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks ligand function. It is indicated to treat patients with mismatch repair deficient (dMMR) or microsatellite instability high (MSI-H). It is also indicated to treat patients with recurrent or advanced endometrial cancer who have used a platinum-containing treatment.
The PD-1-blocking antibody shows a consistent safety and tolerability to similar regimens. Nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, and diarrhea appear to be the most common adverse events of dostarlimab and chemotherapy.
“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 in the treatment of primary advanced or recurrent endometrial cancer,” Abdullah said in the press release.
GSK plc. Jemperli (dostarlimab) RUBY phase III trial met its primary endpoint in a planned interim analysis in patients with primary advanced or recurrent endometrial cancer. News Release. December 2, 2022.