Results of RUBY Trial Show Improved Survival With Jemperli Plus Zejula in Endometrial Cancer

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GSK’s Jemperli (dostarlimab) produced a significant improvement in survival among adults with primary advanced or recurrent endometrial cancer in a Phase III trial.¹ Findings from the RUBY/ENGOT-EN6/GOG3031/NSGO trial show that Jemperli plus standard-of-care chemotherapy with carboplatin and paclitaxel, followed by Jemperli plus Zejula (niraparib) as maintenance therapy, achieved the primary endpoint of progression-free survival (PFS). The combination led to a statistically significant and clinically meaningful benefit across the overall patient population and among a subpopulation of patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors in those with primary advanced or recurrent endometrial cancer.

“Patients with MMRp/MSS primary advanced or recurrent endometrial cancer have few approved treatment options,” Hesham Abdullah, senior vice president, Global Head Oncology, R&D, GSK, said in a press release. “Today’s positive topline results reinforce our approach of building combination therapies with [Jemperli] as the backbone in an effort to improve patient outcomes and options.”¹

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. It has shown potential both as a monotherapy and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options.

The two-part global, randomized, double-blind, multicenter RUBY trial analyzed the Jemperli combination in patients with primary advanced or recurrent endometrial cancer. Part 1 of the trial studied Jemperli plus carboplatin-paclitaxel followed by Jemperli compared with carboplatin-paclitaxel plus placebo followed by placebo. Part 2 of the trial analyzed Jemperli plus carboplatin-paclitaxel followed by Jemperli plus Zejula versus placebo plus carboplatin-paclitaxel followed by placebo. An analysis of the full trial data with the key secondary endpoint of overall survival (OS) is ongoing because the data are immature.

In August, the FDA approved Jemperli with carboplatin and paclitaxel, followed by Jemperli as a monotherapy, for the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test, or microsatellite instability high based on findings from an interim analysis of the first part of the RUBY/ENGOT-EN6/GOG3031/NSGO trial.² The FDA previously approved Jemperli as a single agent in adults with dMMR recurrent or advanced endometrial cancer that has progressed on or after prior treatment with a platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation.

At a median follow-up of 24.8 months (range, 19.2-36.9), the addition of Jemperli to chemotherapy produced a 72% decline in the risk of disease progression or death compared with placebo plus chemotherapy. The estimated 24-month PFS rate was 61.4% compared with 15.7% with placebo. The 24-month OS rate with the Jemperli combination was 83.3% compared with 58.7% with placebo or chemotherapy.³

In terms of safety, grade 3 or higher adverse effects (AEs) were reported in 70.5% of patients administered Jemperli (n = 241) and in 59.8% of patients in the placebo (n = 246) cohort. Serious toxicities were reported in 37.8% and 27.6% of patients, respectively.

The most common any-grade AEs experienced by more than 20% of patients in the investigative and control cohorts were fatigue (51.9% vs 54.5%, respectively), alopecia (53.5% vs 50.0%), nausea (53.9% vs 45.9%), peripheral neuropathy (44.0% vs 41.1%), anemia (37.8% vs 42.3%), arthralgia (35.7% vs 35.0%), constipation (34.4% vs 35.8%), diarrhea (31.1% vs 28.9%), myalgia (26.1% vs 27.6%), hypomagnesemia (21.6% vs 28.5%), peripheral sensory neuropathy (21.2% vs 19.1%), reduced appetite (21.6% vs 17.5%), dyspnea (18.3% vs 20.3%), and rash (22.8% vs 13.8%).

Grade 3 or higher AEs reported in the investigative and control cohorts included anemia (14.9% vs 16.3%), neutropenia (9.5% vs 9.3%), decreased neutrophil count (8.3% vs 13.8%), decreased lymphocyte count (5.4% vs 7.3%), decreased white cell count (6.6% vs 5.3%), hypertension (7.1% vs 3.3%), pulmonary embolism (5.0% vs 4.9%), and hypokalemia (5.0% vs 3.7%), respectively.²

References

1. Jemperli (dostarlimab) plus Zejula (niraparib) combination significantly improved progression-free survival in primary advanced or recurrent endometrial cancer in RUBY Part 2 Phase III trial. GSK. News release. December 18, 2023. Accessed December 18, 2023. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-zejula-combination-significantly-improved-progression-free-survival-in-endometrial-cancer-phase-iii-trial/

2. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GlaxoSmithKline. July 31, 2023. Accessed December 18, 2023. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/

3. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. Published online March 27, 2023. Accessed December 18, 2023. doi:10.1056/NEJMoa2216334