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RUBY

Dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in primary advanced or recurrent endometrial cancer (RUBY, ENGOT-EN6-NSGO/GOG-3031), Part 1

Phase 3N = 494NCT03981796

Population
Adults with primary advanced (stage III or IV) or first recurrent endometrial cancer; 118 of 494 randomised had dMMR/MSI-H tumours
Design
Global, double-blind, placebo-controlled phase 3 trial, Part 1; randomised 1:1. Dostarlimab 500 mg or placebo with carboplatin and paclitaxel every 3 weeks for 6 cycles, then dostarlimab 1000 mg or placebo every 6 weeks for up to 3 years. The FDA notice states that randomisation was stratified by MMR/MSI status, prior external pelvic radiotherapy and disease status. ClinicalTrials.gov lists 785 participants for Parts 1 and 2 together; the papers report 494 randomised in Part 1.
Primary endpoint
PFS, OS
Arms
  • Dostarlimab plus carboplatin-paclitaxel (experimental, n = 245): Dostarlimab 500 mg plus carboplatin (AUC 5 mg per mL per min) and paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, then dostarlimab 1000 mg every 6 weeks for up to 3 years
  • Placebo plus carboplatin-paclitaxel (control, n = 249): Placebo plus carboplatin (AUC 5 mg per mL per min) and paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, then placebo every 6 weeks for up to 3 years
People
Mirza MR, ENGOT-EN6-NSGO/GOG-3031
PFSHR 0.28 (95% CI 0.16–0.50)Δ 24-month PFS+45.7 pointsPFSHR 0.64 (95% CI 0.51–0.80)Δ 24-month PFS+18 pointsOSHR 0.64 (95% CI 0.46–0.87)Δ 24-month OS+15.3 points
Show the numbers
Results reported for RUBY
EndpointAnalysisDostarlimab plus carboplatin-paclitaxelPlacebo plus carboplatin-paclitaxelEffect
PFSdMMR/MSI-H population (118 of 494 randomised)Investigator-assessed progression-free survival according to RECIST 1.1primaryMirza 202361.4% at 2 y (46.3–73.4%)15.7% at 2 y (7.2–27.0%)HR 0.28 (95% CI 0.16–0.50)P<0.001Estimated progression-free survival at 24 months, first interim analysis. Hazard ratio for progression or death.
PFSAll randomised patients (N = 494)Investigator-assessed progression-free survival according to RECIST 1.1primaryMirza 202336.1% at 2 y (29.3–42.9%)18.1% at 2 y (13.0–23.9%)HR 0.64 (95% CI 0.51–0.80)P<0.001Estimated progression-free survival at 24 months, first interim analysis.
OSAll randomised patients (N = 494)interimMirza 202371.3% at 2 y (64.5–77.1%)56% at 2 y (48.9–62.5%)HR 0.64 (95% CI 0.46–0.87)First interim analysis; the abstract states no P value for overall survival. The second interim analysis is a separate result.
OSAll randomised patients (N = 494)interimPowell 2024——HR 0.69 (95% CI 0.54–0.89)P=0.0020Second interim analysis at 51% maturity: 245 randomised to dostarlimab and 249 to placebo. The authors report that the trial met the overall survival dual primary endpoint at this analysis.
OSdMMR/MSI-H population (118 of 494 randomised)interimPowell 2024——HR 0.32 (95% CI 0.17–0.63)P=0.0002 (nominal)Second interim analysis; subgroup result with a nominal P value.
OSpMMR/MSS population (subgroup of the 494 randomised)interimPowell 2024——HR 0.79 (95% CI 0.60–1.04)P=0.0493 (nominal)Second interim analysis; the authors describe a trend in favour of dostarlimab in this subgroup.
OSAll randomised patients (N = 494)interimSource 2024median 44.6 monthsmedian 28.2 months (22.1–35.6)HR 0.69 (95% CI 0.54–0.89)P=0.002 (1-sided)The FDA notice gives the 95% CI of the dostarlimab-arm median as 32.6 months to not reached; the upper bound is not encoded here. The notice does not name the data cut-off; its hazard ratio matches the second interim analysis.
PFSAll randomised patients (N = 494)Investigator-assessed progression-free survival according to RECIST 1.1interimSource 2024median 11.8 months (9.6–17.1)median 7.9 months (7.6–9.5)HR 0.64 (95% CI 0.51–0.80)P<0.0001 (1-sided)The notice does not name the data cut-off.
Results reported for RUBY
EndpointAnalysisDostarlimab plus carboplatin-paclitaxelPlacebo plus carboplatin-paclitaxelEffect
PFSdMMR/MSI-H population (118 of 494 randomised)Investigator-assessed progression-free survival according to RECIST 1.1primaryMirza 202361.4% at 2 y (46.3–73.4%)15.7% at 2 y (7.2–27.0%)HR 0.28 (95% CI 0.16–0.50)P<0.001Estimated progression-free survival at 24 months, first interim analysis. Hazard ratio for progression or death.
PFSAll randomised patients (N = 494)Investigator-assessed progression-free survival according to RECIST 1.1primaryMirza 202336.1% at 2 y (29.3–42.9%)18.1% at 2 y (13.0–23.9%)HR 0.64 (95% CI 0.51–0.80)P<0.001Estimated progression-free survival at 24 months, first interim analysis.
OSAll randomised patients (N = 494)interimMirza 202371.3% at 2 y (64.5–77.1%)56% at 2 y (48.9–62.5%)HR 0.64 (95% CI 0.46–0.87)First interim analysis; the abstract states no P value for overall survival. The second interim analysis is a separate result.
OSAll randomised patients (N = 494)interimPowell 2024——HR 0.69 (95% CI 0.54–0.89)P=0.0020Second interim analysis at 51% maturity: 245 randomised to dostarlimab and 249 to placebo. The authors report that the trial met the overall survival dual primary endpoint at this analysis.
OSdMMR/MSI-H population (118 of 494 randomised)interimPowell 2024——HR 0.32 (95% CI 0.17–0.63)P=0.0002 (nominal)Second interim analysis; subgroup result with a nominal P value.
OSpMMR/MSS population (subgroup of the 494 randomised)interimPowell 2024——HR 0.79 (95% CI 0.60–1.04)P=0.0493 (nominal)Second interim analysis; the authors describe a trend in favour of dostarlimab in this subgroup.
OSAll randomised patients (N = 494)interimSource 2024median 44.6 monthsmedian 28.2 months (22.1–35.6)HR 0.69 (95% CI 0.54–0.89)P=0.002 (1-sided)The FDA notice gives the 95% CI of the dostarlimab-arm median as 32.6 months to not reached; the upper bound is not encoded here. The notice does not name the data cut-off; its hazard ratio matches the second interim analysis.
PFSAll randomised patients (N = 494)Investigator-assessed progression-free survival according to RECIST 1.1interimSource 2024median 11.8 months (9.6–17.1)median 7.9 months (7.6–9.5)HR 0.64 (95% CI 0.51–0.80)P<0.0001 (1-sided)The notice does not name the data cut-off.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOSOSOSOSOSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.280.16–0.5
PFS0.640.51–0.8
OS0.640.46–0.87
OS0.690.54–0.89
OS0.320.17–0.63
OS0.790.6–1.04
OS0.690.54–0.89
PFS0.640.51–0.8
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%020406080100Months (modelled)
  • Dostarlimab plus carboplatin-paclitaxel (experimental)
  • Placebo plus carboplatin-paclitaxel (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsDostarlimab plus carboplatin-paclitaxelPlacebo plus carboplatin-paclitaxel
0100.0%100.0%
2864.7%50.2%
5641.9%25.2%
8427.1%12.7%
11217.5%6.4%
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%0510152025Months (modelled)
  • Dostarlimab plus carboplatin-paclitaxel (experimental)
  • Placebo plus carboplatin-paclitaxel (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsDostarlimab plus carboplatin-paclitaxelPlacebo plus carboplatin-paclitaxel
0100.0%100.0%
766.3%54.1%
1541.4%26.8%
2227.5%14.5%
3017.2%7.2%
Primary publication: Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023;388(23):2145-2158. PubMedDOI

Appears in

Sources

  1. Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023;388(23):2145-2158.

    PubMedDOI

  2. Powell MA, Bjørge L, Willmott L, Novák Z, Black D, Gilbert L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. 2024;35(8):728-738.

    PubMedDOI

  3. FDA. FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA notice dated 1 August 2024 (BLA 761174/S-009).

    Source