GSK announced positive headline results from the planned interim analysis of Part 1 of the RUBY phase III trial investigating Jemperli (dostarlimab) plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by Jemperli compared to chemotherapy plus placebo followed by placebo in adult patients with primary advanced or recurrent endometrial cancer.

The trial met its primary endpoint of investigator-assessed progression-free survival (PFS). It showed a statistically significant and clinically meaningful benefit in the prespecified mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) patient subgroup and in the overall population. A clinically relevant benefit in PFS was also observed in the mismatch repair proficient (MMRp)/microsatellite stable (MSS) patient subgroup.

While the overall survival (OS) data were immature at the time of this analysis, a favourable trend was observed in the overall population, including both the dMMR/MSI-H and MMRp/MSS subgroups.

The safety and tolerability profile of dostarlimab in the RUBY phase III trial was consistent with clinical trials of similar regimens. The most common treatment-emergent adverse events in patients receiving dostarlimab plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anaemia, arthralgia, constipation and diarrhoea.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK said: “Patients with primary advanced or recurrent endometrial cancer have limited treatment options. Long-term outcomes remain poor, and new treatment options are urgently needed to evolve the current standard of care, which is platinum-based chemotherapy. Based on these positive headline results from the RUBY phase III trial, GSK intends to seek regulatory approvals for a potential new indication for dostarlimab in the treatment of primary advanced or recurrent endometrial cancer.”

Regulatory submissions based on the trial results are anticipated in the first half of 2023. Full results from the trial will be published in a medical journal and presented at an upcoming scientific meeting.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.3 Dostarlimab is being investigated in registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with Stage III or IV non-mucinous epithelial ovarian cancer, and patients with other advanced solid tumours or metastatic cancers.

In the US, dostarlimab is indicated for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that have progressed on or following prior treatment with a platinum-containing regimen. Dostarlimab is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. These indications are approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).