Phase III Trial Data Show Meaningful Survival Improvements with Jemperli Combinations for Endometrial Cancer

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Survival data from the Phase III RUBY/ENGOT-EN6/GOG3031/NSGO trial demonstrated statistically significant and clinically meaningful outcomes with combination therapies based around GSK’s Jemperli (dostarlimab) in adults with primary advanced or recurrent endometrial cancer. Separate portions of the trial evaluated Jemperli plus chemotherapy with or without adding maintenance treatment with Zejula (niraparib), which showed a benefit in both overall survival (OS) and progression-free survival (PFS).¹

“The positive data presented today further show how [Jemperli]-based regimens could benefit a broader set of patients with endometrial cancer. The results we’ve seen to date comprise the growing body of evidence supporting the role of [Jemperli] as the backbone of our immuno-oncology development program,” said Hesham Abdullah, senior vice president, global head, Oncology, R&D, GSK, in a press release. “Our goal is to continue to identify ways to use [Jemperli] alone and in combination with other therapies to help improve outcomes for patients with limited treatment 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.

Data released in December 2023 from the RUBY/ENGOT-EN6/GOG3031/NSGO trial showed that Jemperli plus standard-of-care chemotherapy with carboplatin and paclitaxel, followed by Jemperli plus Zejula as maintenance therapy, achieved a statistically significant and clinically meaningful benefit across the overall population of patients with primary advanced or recurrent endometrial cancer and among a subpopulation of patients with mismatch repair proficient (MMRp)/microsatellite stable tumors (MSS), which does not currently have an immunotherapy-based regimen approved for treatment.²

Part 1 of the trial compared Jemperli with standard-of-care chemotherapy followed by Jemperli vs. chemotherapy plus placebo followed by placebo. Part 2 compared Jemperli with standard-of-care chemotherapy, followed by Jemperli plus Zejula maintenance therapy vs. chemotherapy plus placebo followed by placebo. The newly released findings demonstrated an additional potential benefit with Jemperli plus chemotherapy, with or without the addition of Zejula, in the overall patient population with primary advanced or recurrent endometrial cancer, and in patients with MMRp/MSS tumors.¹

Part 1 of the trial showed a statistically significant and clinically meaningful OS improvement with Jemperli plus chemotherapy compared with placebo plus chemotherapy, which achieved the trial’s primary endpoint. In the overall patient population, the Jemperli combination decreased the risk of death by 31% (Hazard Ratio [HR]: 0.69; [95% CI: 0.539–0.890]), showing a clinically meaningful median OS improvement of 16.4 months, at 44.6 months among patients administered the Jemperli combination vs. 28.2 months with placebo.

Among patients with MMRp/MSS tumors, the Jemperli combination lowered the risk of death by a clinically meaningful 21% (HR: 0.79; [95% CI: 0.602–1.044]), with an improvement of seven months in median OS at 34.0 months compared with 27.0 months with placebo.

“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,” RUBY principal investigator Matthew Powell, MD, Division of Gynecologic Oncology, Washington University School of Medicine, said in a press release. “As a clinician, I celebrate the results of the RUBY Part 1 trial presented today, which show how [Jemperli] added to chemotherapy could potentially benefit a broader set of patients with this type of cancer.”¹

In Part 2 of the trial, Jemperli plus Zejula maintenance therapy achieved the primary endpoint, showing a significantly improved PFS in first-line primary advanced or recurrent endometrial cancer. In the overall patient population, Jemperli plus Zejula produced a statistically significant 40% decrease in the risk of disease progression or death (HR: 0.60 [95% CI: 0.43–0.82]), with a clinically meaningful 6.2-month improvement in median PFS at 14.5 months vs. 8.3 months with placebo. Among patients with MMRp/MSS tumors, the Jemperli plus Zejula combination produced a statistically significant 37% decrease in the risk of disease progression or death (HR: 0.63 [95% CI: 0.44–0.91]), as well as a clinically meaningful 6.0-month improvement in median PFS at 14.3 months compared with 8.3 months with placebo.¹

In terms of safety, the profiles of Jemperli plus carboplatin-paclitaxel and Jemperli plus carboplatin-paclitaxel followed by Jemperli plus Zejula were consistent with the previously established safety profiles of each individual drug.

“In RUBY Part 2, we observed that the use of Jemperli in combination with Zejula in the maintenance therapy setting further improved progression-free survival versus placebo for patients with primary advanced or recurrent endometrial cancer,” RUBY principal investigator Mansoor Raza Mirza, MD, chief oncologist, Copenhagen University Hospital, Denmark, said in the release. “These findings are particularly important for patients who have MMRp/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 Zejula maintenance to address unmet medical need for these patients.”¹

References

1. Positive RUBY phase III data show potential for Jemperli (dostarlimab) combinations in more patients with primary advanced or recurrent endometrial cancer. GSK. News release. March 15, 2024. Accessed March 18, 2024. https://www.gsk.com/en-gb/media/press-releases/positive-ruby-phase-iii-data-show-potential-for-jemperli-dostarlimab-combinations-in-more-patients-with-primary-advanced-or-recurrent-endometrial-cancer/

2. 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 March 18, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-zejula-combination-significantly-improved-progression-free-survival-in-endometrial-cancer-phase-iii-trial/