The phase 2 RUBY clinical trial has met its primary end point with dostarlimab-gxly given after chemotherapy achieving progression-free survival improvement in adult patients with primary advanced or recurrent endometrial cancer.
Dostarlimab-gxly after chemotherapy demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) in adult patients with primary advanced or recurrent endometrial cancer vs placebo plus chemotherapy, according to findings from the RUBY clinical trial (NCT03981796).1
Achievement of the study’s primary end point of PFS was announced in a press release by GSK plc. RUBY is now the only study of patients with primary advanced or recurrent endometrial cancer treated in the frontline setting to demonstrate PFS improvement with an immuno-oncology (IO) agent in combination with chemotherapy.
The PFS benefit observed with dostarlimab and chemotherapy was not only shown in the overall study population, but also in patients with prespecified mismatch repair deficient (dMMR) disease and microsatellite instability-high (MSI-H) disease. Patients with proficient MMR (MMRp) and microsatellite stable disease (MSS) also derived benefit from the investigational combination.
Moreover, the study showed a trend toward overall survival (OS) benefit in the intent-to-treat (ITT) population and the dMMR , MSI-H, MMRp ,and MSS subgroups.
"Limited data was provided in the press release, but RUBY meeting its 1 primary endpoints of benefit in the dMMR/MSI-H population, and the ITT population is an exciting result, David M. O’Malley, MD, professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC – James, told Targeted Oncology™, in a statement. “It appears there was a benefit in the (non-analytical) subgroup of pMMR/MSS. Once the full data are released, the magnitude of difference in each of these subgroups will be important to put into perspective the positive impact of adding dostarlimab to carboplatin and paclitaxel in patients with advanced or recurrent uterine cancer.”
RUBY is an ongoing phase 3, randomized, double-blind, multicenter study of dostarlimab plus carboplatin and paclitaxel vs placebo and carboplatin/paclitaxel being administered to patients with recurrent of primary advanced endometrial cancer. Up to 785 patients will be enrolled in in the 2-part study.2
In addition to the co primary end points of PFS and OS, RUBY is also investigating OS in part 2 of the study, objective response rate, duration of response, disease control rate, patient-reported outcomes, PFS2, the number of patients with adverse events, the number of patients with clinically significant changes in laboratory parameters, physical examination, and electrocardiogram as secondary end points.
To be eligible for the study, female patients must be 18 years of age or older with histologically or cytologically confirmed disease. Before the study, patients must have an ECOG performance status of 0 or 1, and adequate organ function to be eligible.
Dostarlimab is already an FDA-approved therapy for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options based on the positive results from the GARNET trial (NCT02715284). Dostarlimab is also an approved treatment to recurrent of advanced dMMR endometrial cancer based on findings from the same study.
Both FDA approvals were accelerated approvals and continued approval for the indications is contingent upon verification of clinical benefit in confirmatory trials. According to O’Malley, continued approval of dostarlimab may be the first step to help oncologists shift away from the use of chemotherapy in these patients.
“IO therapies in endometrial cancer have drastically changed the treatment paradigm in the recurrent setting for uterine cancer. This result and the other clinical trials that will report will bring immune therapies earlier into the treatment paradigm of uterine cancer, which will likely increase the number of patients who cured and give patients the best opportunity to live longer with a better quality of life. In the future, we may even get to the point of omitting chemotherapy and instead using immune therapies. The goal is to cure more patients of metastatic/recurrent uterine cancer and immune therapies, like dostarlimab, are a key to meeting this goal,” O’Malley stated.
1. Jemperli (dostarlimab-gxly) RUBY phase III trial met its primary endpoint in a planned interim analysis in patients with primary advanced or recurrent endometrial cancer. News release. GSK plc. December 2, 2022. Accessed December 2, 2022. https://bit.ly/3OUY9um
2. A study to evaluate dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in participants with recurrent or primary advanced endometrial cancer (RUBY). Clincaltrials.gov. Updated August 12, 2022. Accessed December 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03981796?term=RUBY+dostarlimab&draw=2&rank=1