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RUBY 4-year OS — Dostarlimab + chemo in 1L advanced/recurrent endometrial cancer

Abstract: Plenary III · Session: Plenary III, Sunday April 12, 2026 · Simultaneous publication: TBD (likely NEJM or JCO mature OS update)

Headline: Mature 4-year OS in the dMMR/MSI-H subgroup shows HR 0.32 — a 68% mortality reduction, with ~73% of patients alive at 4 years; MMRp subgroup HR 0.79 with 7-mo median OS gain. Confirms dostarlimab + carboplatin/paclitaxel as 1L SOC for dMMR endometrial cancer.

At a glance

  • Sponsor / cooperative groups: GSK · ENGOT-EN6-NSGO / GOG-3031
  • PI / presenter: Plenary III, Apr 12 (presenter TBD)
  • NCT ID: NCT03981796
  • Phase / arms / N: Phase 3 randomized double-blind; 494 patients (245 dostarlimab + chemo vs 249 placebo + chemo)
  • Primary endpoint(s): PFS (primary); OS (key secondary, mature 4-yr update at SGO 2026)
  • Indication / line: 1L advanced (Stage III/IV) or recurrent endometrial cancer, all-comer with dMMR primary analysis subgroup
  • Comparator: Placebo + carboplatin/paclitaxel followed by placebo maintenance
  • Session: Plenary III (Day 3, Apr 12)

Headline result

In the dMMR/MSI-H subgroup, 4-year OS HR 0.32 (95% CI 0.17–0.63) — 68% mortality reduction with ~73% 4-year OS in the dostarlimab arm. In the MMRp subgroup, HR 0.79 (95% CI 0.60–1.04) with 7-mo median OS gain — trend toward benefit. The dMMR survival curve is among the steepest in any solid-tumor Phase 3 mature OS readout. No new safety signals.

Mechanism / class

Dostarlimab is a humanized IgG4 anti–PD-1 monoclonal antibody. RUBY is the cycle-defining mature OS confirmation of the chemo-immunotherapy 1L paradigm in endometrial cancer (alongside NRG-GY018 with pembrolizumab).

Trial design deep dive

Study architecture: Phase 3 randomized double-blind placebo-controlled, 1:1 to dostarlimab 500 mg IV Q3W + carboplatin AUC5 / paclitaxel 175 mg/m² for 6 cycles → dostarlimab 1,000 mg Q6W maintenance up to 3 years, vs placebo + chemo → placebo maintenance. 494 patients total (245 vs 249). Stratification by MMR/MSI status, prior anti-cancer therapy, and disease status (recurrent vs primary advanced) — the MMR stratification is the design feature that enabled the dMMR primary analysis subgroup to be powered separately.

Endpoint definitions: PFS by investigator assessment per RECIST 1.1 (primary, with dMMR subgroup as primary analysis population); OS (key secondary, gated on PFS positivity per hierarchical testing). The 4-year mature OS update reported at SGO 2026 follows the original PFS readout (SGO/NEJM 2023) and the interim OS update (ESMO 2024).

Key subgroup analyses: dMMR/MSI-H subgroup HR 0.32 (the headline plateau) vs MMRp HR 0.79. POLE-mutated and p53-abnormal molecular subgroups (per ProMisE/TCGA endometrial classifier) reserved for ASCO 2026 follow-up. Geographic, age, BMI, and prior-therapy subgroups TBD in plenary deck.

Comparator context: Carboplatin/paclitaxel + placebo with placebo maintenance reflects pre-2023 SOC. The 4-year placebo-arm OS in dMMR (TBD per slide) provides the historical floor against which the 73% dostarlimab plateau is judged.

FDA implications: Confirmatory — accelerated approval (dMMR) and full approval (all-comer) already in place; the 4-yr OS locks in the magnitude of benefit and rules out late curve crossing, supporting durable NCCN preferred status.

Discussant takeaway

Plenary III framing: the dMMR OS curve flattens to ~73% at 4 years — exceptional plateau-like behavior consistent with durable immune control. Reinforces molecular triage (dMMR/MMRp split) as the cornerstone of endometrial therapy selection.

Practice-changing verdict

Yes (confirmatory). Dostarlimab + chemo was already 1L SOC for dMMR endometrial post-RUBY interim; the 4-yr mature OS locks in the magnitude of benefit and rules out late curve crossing. NCCN endometrial guidelines reinforced.

  • Other SGO 2026: D-RT (dostarlimab + RT, chemo-free adjuvant dMMR); GOG-3039 (abemaciclib + letrozole HR+ endometrial)
  • AACR 2026: dMMR immunobiology and POLE-mut sessions
  • ASCO 2026: Expected long-term safety + biomarker subgroup analyses (POLE-mut, p53-abn)
  • ESMO 2026: European subgroup follow-up

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