In a significant development for patients with primary advanced or recurrent endometrial cancer, GSK plc (LSE/NYSE: GSK) has disclosed promising outcomes for Jemperli (dostarlimab-gxly) from the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial. The trial’s Part 1 and Part 2 findings, which showcase notable improvements in overall survival (OS) and progression-free survival (PFS), respectively, were unveiled in a late-breaking plenary session at the Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer, held from March 16-18.

The primary focus of the RUBY phase III trial program is to ascertain the efficacy of Jemperli in combination with chemotherapy, with or without the addition of Zejula (niraparib) maintenance therapy, in treating this patient demographic. Part 1 of the trial explores the impact of dostarlimab-gxly combined with standard-of-care chemotherapy followed by dostarlimab-gxly maintenance versus chemotherapy plus placebo. Part 2 evaluates the efficacy of adding niraparib to the treatment regimen post-chemotherapy.

The trial’s results are particularly noteworthy, with Part 1 revealing a statistically significant 31% reduction in the risk of death and a 16.4-month increase in median OS for patients treated with dostarlimab-gxly plus chemotherapy, compared to those receiving chemotherapy plus placebo. Moreover, a clinically meaningful trend towards reduced mortality was observed in patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, a subgroup for which no approved immuno-therapy-based regimens currently exist.

Dr. Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D at GSK, commented on the results, highlighting the potential for dostarlimab-gxly-based regimens to benefit a broader set of patients with endometrial cancer. The data presented reaffirm GSK’s commitment to expanding the utility of dostarlimab-gxly within its immuno-oncology development program.

Matthew Powell, MD, Division of Gynecologic Oncology at Washington University School of Medicine and US principal investigator of the RUBY trial, emphasized the significance of these findings. According to Dr. Powell, RUBY Part 1 is the first clinical trial to demonstrate a statistically significant and clinically meaningful improvement in OS for an immuno-oncology therapy combined with chemotherapy in this patient population.

The safety and tolerability profiles of the combined treatment regimens were generally in line with the known safety profiles of the individual medicines. GSK anticipates regulatory submission acceptance by the US Food and Drug Administration for an expanded indication in the overall population based on RUBY Part 1 data in the first half of this year.

RUBY Part 2 further demonstrated the efficacy of adding niraparib to dostarlimab-gxly in the maintenance setting, significantly improving PFS in patients with primary advanced or recurrent endometrial cancer. This addition has shown to reduce the risk of disease progression or death by 40% in the overall population and by 37% in the MMRp/MSS population, presenting a substantial improvement over chemotherapy alone.

Dr. Mansoor Raza Mirza, Chief Oncologist at Copenhagen University Hospital, Denmark, and RUBY principal investigator, pointed out the importance of these findings for patients with MMRp/MSS tumors, underlining the potential of the combined maintenance therapy to meet unmet medical needs in this group.

The RUBY trial’s outcomes offer promising insights into the potential of dostarlimab-gxly, both alone and in combination with other therapies, to improve treatment outcomes for patients with limited options. As research continues, these findings may pave the way for new standards in endometrial cancer care, emphasizing the importance of innovative treatment strategies in oncology.

  chemotherapy, dostarlimab-gxly, Endometrial Cancer Treatment, GSK plc, Immuno-Oncology Development, Jemperli, Niraparib Maintenance, Overall Survival, Progression-Free Survival, RUBY Phase III Trial, Society of Gynecologic Oncology, Zejula