Endometrial cancer, positive news in therapy from Ruby 1 and 2 studies

The only immuno-oncology combination to show statistically and clinically significant overall survival across the entire patient population with advanced or recurrent primary endometrial cancer is dostarlimab plus chemotherapy. This is indicated by the data from the Ruby study, released today by GSK and presented in a plenary session at the Annual Meeting of the Society of Gynecologic Oncology on Women's Cancer which ended on March 18.

The statistically and clinically significant overall survival results of part 1 and those of progression-free survival of part 2 of the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO study – reports a note – show a 31% reduction in the risk of death and a 16.4 month improvement in median survival with dostarlimab plus chemotherapy compared to chemotherapy, across the entire population. Additionally, there was a 37% reduction in the risk of disease progression or death and an improvement in median progression-free survival at 6 months with the addition of niraparib to dostarlimab maintenance therapy after dostarlimab plus chemotherapy, compared to chemotherapy alone. in the mismatch repair capacity (MMRp)/microsatellite stable (MSS) tumor population, where treatment options are still needed.

The objective of the Phase 3 Ruby study program – recalls GSK – is to evaluate which patients with advanced or recurrent primary endometrial cancer could potentially benefit from treatment with dostarlimab plus chemotherapy, with or without the addition of maintenance niraparib. Part 1 of the study is evaluating dostarlimab plus standard chemotherapy (carboplatin-paclitaxel) followed by dostarlimab, versus chemotherapy plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus standard chemotherapy, followed by dostarlimab plus niraparib as maintenance therapy, versus chemotherapy plus placebo followed by placebo. The safety and tolerability profiles of dostarlimab plus carboplatin-paclitaxel and dostarlimab plus carboplatin-paclitaxel, followed by dostarlimab plus niraparib, were found to be comparable to the known safety profiles of the individual medicinal products.

Previous data have shown a statistically significant and clinically meaningful improvement in progression-free survival with dostarlimab plus chemotherapy compared to chemotherapy alone in first-line mismatch repair (dMMR)-deficient/high microsatellite instability (MSI) advanced or recurrent primary endometrial cancer -H). This data has led to regulatory approvals in the US, EU and some other countries.

The latest results presented show an additional potential benefit of dostarlimab plus chemotherapy, with or without the addition of niraparib, in the overall population of patients with advanced or recurrent primary endometrial cancer, including patients with MMRp/MSS tumors, for which currently no There are approved immunotherapy-based regimens.

On part 1 of the study, “the positive data – says Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK – further shows how dostarlimab-based regimens could benefit a broader group of patients with endometrial cancer. The results we have seen so far add to the evidence supporting dostarlimab's role as the backbone of our immuno-oncology development program. Our goal is to continue to identify ways to use dostarlimab alone and in combination with other therapies to help improve outcomes for patients with limited treatment options.”

According to the U.S. principal investigator of the Ruby study, Matthew Powell, Division of Gynecologic Oncology, University of Washington School of Medicine, “Ruby 1 is the first clinical trial to show a statistically and clinically significant improvement in overall survival for an immunotherapy oncology in combination with chemotherapy in the overall population of patients with advanced primary disease or recurrent endometrial cancer. As a physician, I appreciate these results showing how dostarlimab added to chemotherapy could potentially benefit a larger group of patients with this type of cancer.” Based on the Ruby Part 1 data, GSK expects to have the US Food and Drug Administration accept a submission for an expanded indication in the overall population in the first half of this year.

On part 2 of the study, Mansoor Raza Mirza, chief oncologist at Copenhagen University Hospital, Denmark, and principal investigator of Ruby, notes that “the use of dostarlimab in combination with niraparib in the context of maintenance therapy further improved survival progression-free versus placebo for patients with advanced or recurrent primary endometrial cancer. These findings are particularly important for patients with MMRp/MSS tumors. The increased initial benefit observed with an immuno-oncology regimen plus chemotherapy responds to unmet medical needs of these patients”.