Dostarlimab/Niraparib Improves PFS Outcomes in Advanced Endometrial Cancer

It was reported that the safety profile of dostarlimab combined with chemotherapy plus maintenance dostarlimab and niraparib in the phase 3 RUBY trial (NCT03981796) was found to be primarily consistent with the known profiles of each drug.

Treatment with dostarlimab-gxly (Jemperli) plus carboplatin/paclitaxel followed by maintenance dostarlimab and niraparib (Zejula) resulted in a progression-free survival (PFS) benefit in patients with primary advanced or recurrent endometrial cancer, according to a press release on findings from part 2 of the phase 3 RUBY trial (NCT03981796).¹

The trial met its primary end point with a statistically significant, clinically meaningful improvement in PFS with the dostarlimab combination over placebo and chemotherapy in both the general patient population and a subgroup of patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) disease. Overall survival (OS) data are currently immature, although investigators indicate that a full analysis of the study’s data is expected.

Moreover, it was reported that the safety profile of dostarlimab combined with chemotherapy plus maintenance dostarlimab and niraparib was found to be primarily consistent with the known profiles of each drug.

“Patients with pMMR/MSS primary advanced or recurrent endometrial cancer have few approved treatment options,” Hesham Abdullah, senior vice president, global head of Oncology, Research & Development at GSK, said in the press release. “Today’s positive topline results reinforce our approach of building combination therapies with dostarlimab as the backbone in an effort to improve patient outcomes and options.”

Investigators intend to present the study’s full findings at an upcoming scientific meeting in addition to publishing them in a medical journal and showing them to regulatory authorities.

The study’s secondary end points include OS, overall response rate, duration of response, disease control rate, patient-reported outcomes, and PFS2.

Data from the RUBY trial previously read out at the 2023 European Society for Medical Oncology Congress (ESMO).² Findings from the readout indicated that the PFS rate among patients in the mismatch repair deficient/microsatellite instability–high population was 57.0% in the dostarlimab arm compared with 10.2% in the placebo arm (HR, 0.31; 95% CI, 0.17-0.56). Additionally, in the TP53-mutated population, the PFS rate was 32.4% vs 17.8% in each respective arm (HR, 0.55; 95% CI, 0.30-0.99). Lastly, among patients with no specific molecular profile, the PFS rate was 31.0% vs 20.1%, respectively.

The study had an estimated enrollment of 470 patients and an actual enrollment of 787 patients.

To be included, patients needed to be at least 18 years of age with histologically or cytologically confirmed endometrial cancer with advanced or recurrent disease. Additional enrollment criteria included having stage III to IV disease or first recurrence. Additional inclusion criteria included an ECOG performance status of 0 or 1, adequate organ function, normal blood pressure or adequately treated hypertension, and an ability to take oral medications.

Those who previously received adjuvant or neoadjuvant treatment with an anticancer systemic therapy for stage III or IV disease were ineligible for enrollment. Additional exclusion criteria included more than 1 recurrence, uncontrolled central nervous system metastases, and not adequately recovering from adverse effects or complications from any previous major surgery before beginning treatment.

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. News release. GSK. December 18, 2023. Accessed December 18, 2023. https://bit.ly/3v2UoNI
2. Mirza MR, Sharma S, Herrstedt J, et al. Dostarlimab + chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: analysis of progression-free survival and overall survival outcomes by molecular classification in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract 740MO.