Statistically significant and clinically meaningful overall survival results from Part 1 and progression-free survival results from Part 2 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial in adult patients with primary advanced or recurrent endometrial cancer were presented in a late-breaking plenary session at the Society of Gynecologic Oncology’s (SGO) 2024 Annual Meeting on Women’s Cancer.
The goal of the RUBY phase III trial program is to evaluate which patients with primary advanced or recurrent endometrial cancer could potentially benefit from treatment with dostarlimab-gxly plus chemotherapy, with or without the addition of niraparib maintenance. Part 1 of the RUBY phase III trial is investigating dostarlimab plus standard-of-care chemotherapy (carboplatin/paclitaxel) followed by dostarlimab compared to chemotherapy plus placebo followed by placebo. Part 2 of the RUBY phase III trial is evaluating dostarlimab plus standard-of-care chemotherapy, followed by dostarlimab plus niraparib as maintenance therapy compared to 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 generally consistent with the known safety profiles of the individual medicines.
Previous data showed a statistically significant and clinically meaningful improvement in progression-free survival with dostarlimab plus chemotherapy vs chemotherapy alone in front-line mismatch repair–deficient/microsatellite instability–high primary advanced or recurrent endometrial cancer. These data led to regulatory approvals for this patient population in the United States, European Union, and certain other countries. Data presented at SGO 2024 show an additional potential benefit of dostarlimab plus chemotherapy, with or without the addition of niraparib, in the overall population of patients with primary advanced or recurrent endometrial cancer, including patients with mismatch repair–proficient (pMMR)/microsatellite-stable (MSS) tumors, for which there are currently no approved immunotherapy-based regimens.
RUBY Part 1 Results
In an update on Part 1 of the RUBY trial, a statistically significant and clinically meaningful improvement in overall survival was observed for dostarlimab plus chemotherapy vs placebo plus chemotherapy, meeting a primary endpoint of the study.
In the overall population, dostarlimab plus chemotherapy vs chemotherapy alone showed:
- A statistically significant reduction in the risk of death by 31% (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.539–0.890)
- A clinically meaningful improvement of 16.4 months in median overall survival (44.6 months vs 28.2 months).
In a prespecified exploratory analysis of the pMMR/MSS population, dostarlimab plus chemotherapy vs chemotherapy alone showed:
- A clinically meaningful trend in reduced risk of death by 21% (HR = 0.79, 95% CI = 0.602–1.044)
- A clinically meaningful improvement of 7 months in median overall survival (34.0 months vs 27.0 months).
Presenting author Matthew Powell, MD, of the Division of Gynecologic Oncology at Washington University in St. Louis School of Medicine, and U.S. principal investigator of the RUBY trial, said, “RUBY Part 1 is the first clinical trial to show a statistically significant and clinically meaningful improvement in overall survival for an immuno-oncology therapy in combination with chemotherapy in the overall population of patients with primary advanced or recurrent endometrial cancer. As a clinician, I celebrate the results of the RUBY Part 1 trial … which show how dostarlimab added to chemotherapy could potentially benefit a broader set of patients with this type of cancer.”
In RUBY Part 1, grade 3 or higher and serious treatment-emergent adverse events were approximately 12% higher in the dostarlimab plus carboplatin/paclitaxel arm (treatment arm) compared with the placebo plus carboplatin/paclitaxel arm (control arm). The nature and types of immune-related adverse events in the dostarlimab plus chemotherapy safety profile were consistent with the mechanism of action of dostarlimab and similar to those reported for other PD-1/PD-L1 inhibitors. In the trial, 40.7% of participants in the treatment arm and 16.3% of participants in the control arm had immune-related adverse events assessed by the investigator as related to dostarlimab or placebo, respectively. Discontinuation of dostarlimab or placebo due to a treatment-emergent adverse event occurred in 19.1% of patients in the treatment arm and 8.1% of patients in the control arm.
RUBY Part 2 Results
In an update on Part 2 of the RUBY trial, the addition of niraparib to dostarlimab in the maintenance setting significantly improved progression-free survival in first-line primary advanced or recurrent endometrial cancer compared to chemotherapy alone, meeting the primary endpoint of the trial.
In the overall population, dostarlimab plus chemotherapy followed by dostarlimab plus niraparib compared to placebo plus chemotherapy followed by placebo showed:
- A statistically significant reduction in the risk of disease progression or death by 40% (HR = 0.60, 95% CI = 0.43–0.82)
- A clinically meaningful improvement of 6.2 months in median progression-free survival (14.5 months vs 8.3 months).
In the pMMR/MSS population, dostarlimab plus chemotherapy followed by dostarlimab plus niraparib compared to placebo plus chemotherapy followed by placebo showed:
- A statistically significant reduction in the risk of disease progression or death by 37% (HR = 0.63, 95% CI = 0.44–0.91)
- A clinically meaningful improvement of 6.0 months in median progression-free survival (14.3 months vs 8.3 months).
Mansoor Raza Mirza, MD, Chief Oncologist at Copenhagen University Hospital, and RUBY principal investigator, said, “In RUBY Part 2, we observed that the use of dostarlimab in combination with niraparib in the maintenance therapy setting further improved progression-free survival vs placebo for patients with primary advanced or recurrent endometrial cancer. These findings are particularly important for patients who have pMMR/MSS tumors as the data help build on the initial benefit observed with an immuno-oncology plus chemotherapy regimen, reflecting the potential for the addition of niraparib maintenance to address unmet medical need for these patients.”
Mansoor Raza Mirza, MD
In RUBY Part 2, grade 3 or higher and serious treatment-emergent adverse events were approximately 36% and 24% higher, respectively, in the dostarlimab plus chemotherapy followed by dostarlimab plus niraparib arm (treatment arm) compared with the placebo plus chemotherapy followed by placebo arm (control arm). In the trial, 36.6% of participants in the treatment arm and 6.3% of participants in the control arm had immune-related adverse events assessed by the investigator as related to dostarlimab or placebo, respectively. No cases of myelodysplastic syndrome/acute myeloid leukemia were reported; other secondary primary malignancies occurred in one patient each in both treatment arms. Discontinuation of dostarlimab or placebo due to a treatment-emergent adverse events occurred in 24.1% of patients in the treatment arm and 5.2% of patients in the control arm. Discontinuation of niraparib or placebo due to a treatment-emergent adverse event occurred in 15.7% of patients in the treatment arm and 4.2% of patients in the control arm.
