Clinical trialPhase 3Endometrial (womb) cancer

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer

N Engl J Med · 2023494 patients (245 in the dostarlimab group and 249 in the placebo group); 118 patients with dMMR/MSI-H tumours

Mirza MR, Chase DM, Slomovitz BM, et al. N Engl J Med. 2023. 388:2145-2158

Study type: Clinical trial
Study name: RUBY (ENGOT-EN6/GOG-3031)
Phase: Phase 3
Design: Global, randomised, double-blind, placebo-controlled phase 3 trial (part 1); 1:1 randomisation
Sample size: 494 patients (245 in the dostarlimab group and 249 in the placebo group); 118 patients with dMMR/MSI-H tumours
Source: N Engl J Med · 2023
Trial registration: NCT03981796

In plain words

Women with advanced or recurrent womb cancer received standard chemotherapy with either the immunotherapy dostarlimab or a placebo, and then continued dostarlimab or placebo for up to 3 years. Immunotherapy delayed the growth of the cancer and, in later follow-up, also helped patients live longer; the benefit was largest in tumours with a DNA repair defect (dMMR). Severe side effects were more frequent in the immunotherapy group.

Key results

61.4% vs 15.7%

dMMR/MSI-H: 24-month progression-free survival

HR 0.28 (95% CI 0.16–0.50); P<0.001

36.1% vs 18.1%

Overall population: 24-month progression-free survival

HR 0.64 (0.51–0.80); P<0.001

71.3% vs 56.0%

Overall population: 24-month overall survival (first interim analysis)

HR 0.64 (0.46–0.87)

HR 0.69

Overall population: overall survival at the second interim analysis (Ann Oncol 2024)

95% CI 0.54–0.89; P=0.0020; 51% maturity

HR 0.32

dMMR/MSI-H: overall survival (second interim analysis)

0.17–0.63; nominal P 0.0002

HR 0.79

pMMR/MSS: overall survival (second interim analysis)

0.60–1.04; nominal P 0.0493

Drugs in this study:Carboplatin (Paraplatin)Paclitaxel (Taxol)

Dose and schedule cards

Dostarlimab + carboplatin–paclitaxel (RUBY)

First line: primary stage III or IV or first recurrence; FDA indication regardless of MMR statusOn the page “Endometrial (womb) cancer” · Advanced or recurrent disease: first line

First line: primary stage III or IV or first recurrence; FDA indication regardless of MMR status

Drug	Dose	Route	Schedule
With chemotherapy: 6 cycles every 21 days
Dostarlimab	500 mg (30-minute infusion)	IV	Day 1, before chemotherapy
Carboplatin	AUC 5	IV	Day 1
Paclitaxel	175 mg/m²	IV	Day 1
Maintenance
Dostarlimab	1000 mg	IV	Every 6 weeks

Cycle length: 21 days for the first 6 cycles, then every 6 weeks
Duration: Until progression, unacceptable toxicity or up to 3 years

Dose source: the paper and the FDA label. Severe and serious adverse events were more frequent with dostarlimab; the most common adverse events were nausea (53.9%), alopecia (53.5%) and fatigue (51.9%). Regimen page: Dostarlimab with carboplatin–paclitaxel

On the page “Endometrial (womb) cancer” · Advanced or recurrent disease: first line

RUBY

Advanced or recurrent endometrial cancerOn the page “Dostarlimab with carboplatin-paclitaxel in endometrial cancer (RUBY)”

Advanced or recurrent endometrial cancer

Drug	Dose	Route	Schedule
Phase 1: 6 cycles
Dostarlimab	500 mg	IV	Day 1
Carboplatin	AUC 5	IV	Day 1
Paclitaxel	175 mg/m²	IV	Day 1
Phase 2
Dostarlimab	1000 mg	IV	Every 6 weeks

Cycle length: Chemotherapy every 21 days; maintenance every 6 weeks
Duration: Dostarlimab up to 3 years

As in RUBY.

Dose source:.

On the page “Dostarlimab with carboplatin-paclitaxel in endometrial cancer (RUBY)”

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Dostarlimab + carboplatin–paclitaxel (245 patients)

Dostarlimab 500 mg IV (30-minute infusion, before chemotherapy) with carboplatin AUC 5 and paclitaxel 175 mg/m² every 3 weeks for 6 cycles; then dostarlimab 1000 mg IV every 6 weeks for up to 3 years.

2Placebo + carboplatin–paclitaxel (249 patients)

Placebo with the same carboplatin and paclitaxel every 3 weeks for 6 cycles; then placebo every 6 weeks for up to 3 years.

Source of the regimen details: Abstract of the paper and the FDA label for Jemperli (infusion time and order of administration)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with primary advanced stage III or IV endometrial cancer or first recurrence. Of 494 patients, 118 (23.9%) had mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) tumours.

Endpoints

Dual primary endpoints: progression-free survival assessed by the investigator per RECIST version 1.1, and overall survival. Safety was also assessed.

Safety and side effects

The most common adverse events that occurred or worsened during treatment: nausea (53.9% in the dostarlimab group and 45.9% in the placebo group), alopecia (53.5% and 50.0%) and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group; details are in the full text. At the second interim analysis, the safety profile was consistent with the first analysis.

Clinical significance and place in guidelines

RUBY was the first trial to show a significant overall survival benefit in the overall population from adding a PD-1 inhibitor to first-line carboplatin–paclitaxel. The FDA has approved dostarlimab with carboplatin and paclitaxel, followed by dostarlimab alone, for primary advanced or recurrent endometrial cancer. The ESGO/ESTRO/ESP 2025 guideline recommends this approach in MMRd disease [I, A] and lists it as an option in non-MMRd disease [I, B].

Limitations

Overall survival results were reported at the second interim analysis with 51% maturity. In pMMR/MSS disease the overall survival benefit was smaller, and the P value reported for this subgroup is only nominal (0.0493). Severe and serious adverse events were more frequent with dostarlimab. The trial was funded by the manufacturer (GSK).

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.