Positive headline results from part 2 of the RUBY/ENGOT-EN6/GOG3031/NSGO trial support the potential use of dostarlimab as the backbone for therapies in mismatch repair proficient/microsatellite stable primary advanced or recurrent endometrial cancer.
Dostarlimab-gxly (Jemperli) in combination with standard-of-care chemotherapy followed by dostarlimab plus niraparib (Zejula) as maintenance therapy in adult patients with primary advanced or recurrent endometrial cancer showed statistically significant and clinically meaningful improvements in the primary end point of progression-free survival (PFS), according to planned analysis of part 2 of the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796).1
With benefits in PFS observed in both the overall patient population and in a subpopulation of patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors, the trial met its primary end point. These findings reinforce the potential of utilizing dostarlimab as a backbone in immuno-oncology-based combination therapies to improve patient outcomes and options.
“[The RUBY trial] is transformative. This plus another trial that was done, both are consistent and show that adding checkpoint inhibition to the upfront treatment for patients with advanced recurrent endometrial cancer is really the new standard-of-care,” Matthew A. Powell, MD, a professor of obstetrics and gynecology, chief of the division of gynecologic oncology at Washington University School of Medicine, and gynecologic oncologist at Siteman Cancer Center, previously told Targeted OncologyTM, in an interview.
In addition to the PFS findings, the safety profile of dostarlimab combined with carboplatin and paclitaxel, followed by dostarlimab plus niraparib, was generally consistent with the known safety profiles of the individual agents.
An analysis of the full trial data is ongoing and continues to evaluate the key secondary end point of overall survival (OS). The full findings from this analysis of part 2 of the study will be presented at an upcoming scientific meeting, published in a medical journal, and shared with regulatory authorities.
In July 2023, dostarlimab plus carboplatin and paclitaxel was approved by the FDA for patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H).2
This regulatory decision was supported by the randomized, double-blind placebo-controlled phase 3 RUBY trial which showed that dostarlimab given with standard chemotherapy yielded better outcomes than placebo with carboplatin and paclitaxel, according to an assessment conducted by independent central review. (BICR). The primary analysis of RUBY was published in the New England Journal of Medicine.3
The 2-part, randomized, double-blind, multicenter, phase 3 RUBY trial is evaluating dostarlimab in patients with primary advanced or recurrent endometrial cancer.1 In the first part of the study, dostarlimab plus carboplatin and paclitaxel followed by dostarlimab was compared with carboplatin and paclitaxel plus placebo followed by placebo. In part 2, investigators are evaluating dostarlimab plus carboplatin and paclitaxel followed by dostarlimab plus niraparib vs placebo plus carboplatin and paclitaxel followed by placebo.
In the first part of the RUBY trial, a broad population was included. These were patients with various histologies that are often excluded from clinical trials. Approximately 10% of patients had carcinosarcoma and 20% had serous carcinoma.
The dual primary end points evaluated in part 1 were investigator-assessed PFS based on the RECISTv1.1 and OS. In part 2, the primary end point is investigator-assessed PFS in the overall population. Additional end points include PFS in the MMRp/MSS population, and OS in the overall population. For both parts, investigators also are assessing PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, safety, and tolerability.