Phase III RUBY trial of Jemperli (dostarlimab) plus chemotherapy meets endpoint of overall survival in patients with primary advanced or recurrent endometrial cancer

The trial met its primary endpoint of overall survival (OS), demonstrating a statistically significant and clinically meaningful benefit in the overall patient population.

A clinically meaningful OS benefit was observed in both prespecified subpopulations in the trial: mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and mismatch repair proficient (MMRp)/microsatellite stable (MSS) patient subgroups. OS is one of two primary endpoints in the RUBY Part 1 trial. Previously, the trial met its other primary endpoint of progression-free survival (PFS), demonstrating a 72% and 36% reduction in the risk of disease progression or death observed in the dMMR/MSI-H population (HR: 0.28 [95% CI: 0.16-0.50]) and overall patient population (HR: 0.64 [95% CI: 0.51–0.80]), respectively.

The safety and tolerability profile of dostarlimab plus carboplatin and paclitaxel was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events ( greater than 25%) in patients receiving dostarlimab plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, diarrhoea and myalgia.

Currently, Jemperli has regulatory approvals in a certain subset of patients with endometrial cancer based on the previously reported positive results for the primary endpoint of progression-free survival in Part 1 of the RUBY trial. In July 2023, Jemperli received FDA approval 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 that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). Jemperli was also approved in the United Kingdom in October 2023 in combination with platinum-containing chemotherapy for the treatment of adult patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy. The application remains under review in the European Union (EU), Australia, Canada, Switzerland and Singapore.

About RUBY RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

The dual-primary endpoints in Part 1 are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and ITT populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma. In Part 2, the primary endpoint is investigator-assessed PFS. Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.