In updated findings from the pivotal phase 3 ENGOT-ENG-NSGO/GOG-3031/RUBY trial (NCT03981796) presented at the 2026 ASCO Annual Meeting, model-based predictions suggested the potential for cure with dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel in patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) primary advanced or recurrent endometrial cancer.1,2
At a median follow-up of 55.6 months (range, 49.9-67.7), descriptive progression-free survival (PFS) analyses were performed in this population from part 1 of the study. Only 4 new events were reported since the first analysis of PFS with an additional 2.5 years of follow-up. The 4-year PFS rates were 57.9% (95% CI, 42.3%-70.6%) in the dostarlimab arm (n = 53) vs 15.7% (95% CI, 7.2%-27.0%) with chemotherapy plus placebo (n = 65); the median PFS was not estimable (NE; 95% CI, 12.2-NE) for the dostarlimab arm vs 7.7 months (95% CI, 5.6-9.7) for the placebo arm (HR, 0.30; 95% CI, 0.17-0.52).
Mixture cure models were fitted to PFS findings to estimate the proportion of patients who had received the dostarlimab regimen and had potential for cure; this analysis revealed that 54% (95% CI, 35%-72%) of patients with dMMR/MSI-H endometrial carcinoma had curative potential with the combination compared with 14% (95% CI 6%-28%) for the placebo arm, representing a 3.9-fold increase in the rate of curative potential.
“These analyses represent the model-based prediction that suggests the potential for curative intent in these patients [with primary advanced or recurrent dMMR/MSI-H] endometrial cancer using [an] immunotherapy plus chemotherapy combination,” lead study author Matthew A. Powell, MD, said in a presentation of the data. “These analyses may assist all of us in communicating long-term survival outcomes in our patients receiving [dostarlimab plus chemotherapy].”
Powell is the Ira C. and Judith Gall Professor of Obstetrics and Gynecology in the Division of Gynecologic Oncology at Washington University School of Medicine in St. Louis, Missouri.
Updated data also showed that the median OS was NE (95% CI, NE-NE) in the dostarlimab arm vs 32.8 months (95% CI, 21.6-NE) in the placebo arm (HR, 0.34; 95% CI, 0.19-0.53). The 4-year OS rates were 72.8% (95% CI, 58.5%-82.9%) and 40.3% (95% CI, 28.2%-52.1%), respectively.
What additional data were generated from the mixture cure models?
Findings also showed that among patients with dMMR/MSI-H disease who were progression-free at 1 year, 2 years, and 3 years, the probabilities of remaining progression-free at 4 years were 88.6% (95% CI, 68.5%–96.2%), 91.7% (95% CI, 70.6%-97.8%), and 91.7% (95% CI, 70.6%-97.8%), respectively. For patients still alive at 1 year, 2 years, and 3 years, the respective probabilities of remaining alive at 4 years were 84.0% (95% CI, 69.3%-92.0%), 88.0% (95% CI, 73.5%-94.8%), and 94.7% (95% CI, 80.6%-98.7%).
When and how are mixture cure models utilized?
Mixtures cure models can serve as an estimate of survival in the presence of a durable survival plateau, taking into account a combination of disease-related mortality and general population mortality.
For the RUBY analysis, investigators applied the mixture cure model to PFS data to estimate a cure rate, which was defined as the proportion of patients with long-term low risk of progression or disease-related mortality.
What was the design of the RUBY trial?
The RUBY trial enrolled patients aged 18 years or older with histologically or cytologically confirmed primary advanced (FIGO stage III or IV) or first recurrent endometrial cancer not amenable to curative therapy.3 Patients were required to have measurable or evaluable disease per RECIST 1.1 criteria in select stage groups, and tumor samples sufficient for MMR and microsatellite status assessment were required.
RUBY Trial Readout at ASCO 2026: Key Points
- In patients with dMMR/MSI-H endometrial cancer, the addition of dostarlimab to chemotherapy improved the 4-year progression-free survival rate to 57.9% (95% CI, 42.3%-70.6%), compared with 15.7% (95% CI, 7.2%-27.0%) for those receiving chemotherapy alone.
- Mixture cure modeling estimates that 54% (95% CI, 35%-72%) of patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer may have the potential for cure when treated with the dostarlimab combination.
- In the overall study population, dostarlimab plus chemotherapy improved the median OS to 44.6 months (95% CI, 32.6-not reached) vs 28.2 months (95% CI, 22.1-35.6) for chemotherapy alone (HR, 0.69; 95% CI, 0.54-0.89).
A total of 607 patients were screened across 113 sites in 19 countries from July 2019 through February 2021; 494 patients were randomly assigned in a 1:1 ratio to receive dostarlimab at 500 mg or placebo intravenously in combination with carboplatin at an area under the curve of 5 mg/mL per minute and paclitaxel at 175 mg/m² every 3 weeks for 6 cycles, followed by dostarlimab at 1000 mg or placebo every 6 weeks for up to 3 years. Of 494 randomly assigned patients, 118 (23.9%) had confirmed dMMR/MSI-H tumors (dostarlimab: n = 53; placebo: n = 65). In the overall population, 47.8% of patients had recurrent disease, 33.6% of patients had primary stage IV disease, and 18.6% of patients had primary stage III disease.
The primary end points were investigator-assessed PFS per RECIST 1.1 criteria in the dMMR/MSI-H and overall populations, and overall survival (OS) in the overall population.
In a recent Peer Exchange program, Gottfried E. Konecny, MD, of UCLA Health, reviewed the design and key efficacy findings of the RUBY trial.4 He described the eligibility criteria, dosing schedule, and the striking outcomes observed in both dMMR and mismatch repair–proficient patient populations.
What prior data from the RUBY study have been reported with dostarlimab?
Data from an interim analysis of part 1 of the study supported the FDA’s decision to first approve dostarlimab in combination with carboplatin and paclitaxel, followed by dostarlimab as a single agent, in adult patients with primary advanced or recurrent endometrial cancer that is dMMR or MSI-H in July 2023.5 At a median follow-up of 24.8 months (range, 19.2-36.9), dostarlimab plus chemotherapy led to a 72% reduction in the risk of disease progression or death vs chemotherapy alone in these patients (HR, 0.28; 95% CI, 0.16-0.50; P < .001). The estimated 24-month PFS rates were 61.4% (95% CI, 46.3%-73.4%) and 15.7% (95% CI, 7.2%-27.0%), respectively.
At the time of the decision, Mansoor Raza Mirza, MD,6 of Copenhagen University Hospital, discussed the significance of the decision with OncLive®:
