Oncology · Clinical trials
Endometrial (Uterine) Cancer Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About endometrial (uterine) cancer — and why its trials are hard
Endometrial cancer is the most common gynecologic malignancy in high-income countries, with rising incidence linked to obesity and aging. Molecular classification (POLE-ultramutated, mismatch-repair-deficient/MSI-H, p53-abnormal, and no-specific-molecular-profile) has transformed how the disease is understood and treated, with dMMR status strongly predicting immunotherapy benefit. Most patients present with early, curable disease, so advanced and recurrent disease trials draw from a smaller, often older and comorbid population. This makes trials hard: accrual of chemo-refractory patients is slow, competing comorbidities (obesity, diabetes, cardiovascular disease) affect tolerability and survival independent of cancer, and the molecular subtypes behave so differently that unselected trials can dilute true effects. Anti-angiogenic and immunotherapy combinations add cumulative toxicity (hypertension, hypothyroidism, immune-related events), challenging dose maintenance. Historical reliance on hormonal therapy and carboplatin-paclitaxel set an efficacy baseline, and endpoints such as overall survival require long follow-up because indolent subtypes progress slowly, whereas serous and p53-mutant tumors behave aggressively.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Lenvatinib + pembrolizumab (Lenvima + Keytruda) | 2019 (accelerated); 2021 (full) | Advanced endometrial carcinoma, not MSI-H/dMMR, after prior systemic therapy | Study 309/KEYNOTE-775 | Overall survival and progression-free survival | All-comers median OS 18.3 vs 11.4 months (HR 0.62); PFS 7.2 vs 3.8 months |
| Dostarlimab (Jemperli) | 2021 (accelerated); 2023 (full) | dMMR recurrent/advanced endometrial cancer after platinum therapy | GARNET | Objective response rate | ORR approximately 45% in dMMR cohort, with durable responses |
| Dostarlimab + chemotherapy (Jemperli) | 2023 (dMMR); 2024 (all-comers) | First-line primary advanced/recurrent endometrial cancer, +carboplatin-paclitaxel | RUBY | Progression-free survival | dMMR/MSI-H 24-month PFS 61.4% vs 15.7% (HR 0.28) |
| Pembrolizumab (Keytruda) | 2022 (tissue-agnostic dMMR/TMB-H) and endometrial-specific | Advanced dMMR/MSI-H endometrial cancer; first-line +chemo (NRG-GY018) | KEYNOTE-158 / NRG-GY018 | ORR; progression-free survival | NRG-GY018 dMMR PFS markedly improved (HR ~0.30) (unverified) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in endometrial (uterine) cancer development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Ridaforolimus (and other mTOR inhibitors) — Phase III maintenance / SUCCEED-type studies | mTOR inhibitors (ridaforolimus, temsirolimus, everolimus) showed only modest activity and never achieved regulatory approval in endometrial cancer | Single-pathway PI3K/AKT/mTOR blockade is bypassed by feedback loops; unselected populations diluted any benefit |
| Selinexor — SIENDO | Selinexor maintenance did not significantly improve PFS in the overall population, though a p53 wild-type subgroup signal prompted further study | Benefit appeared confined to a molecular subset not prespecified as primary, and toxicity limited dosing |
Choosing the right endpoint
Primary endpoints that matter in endometrial (uterine) cancer trials
- Progression-free survival (PFS) — Primary endpoint in KEYNOTE-775, RUBY and NRG-GY018
- Overall survival (OS) — Key confirmatory endpoint; long follow-up needed given indolent subtypes
- Objective response rate (ORR) — Basis for dostarlimab and pembrolizumab accelerated approvals in dMMR disease
- Mismatch-repair (dMMR/MSI-H) status — Central predictive biomarker stratifying immunotherapy trials
- Molecular subtype (POLE, p53, NSMP) — Increasingly used for enrichment and prognostic stratification
How iNGENū runs endometrial (uterine) cancer trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Endometrial (Uterine) Cancer clinical trials — FAQs
Why is mismatch-repair status important in endometrial cancer?
What is the lenvatinib plus pembrolizumab combination used for?
How has first-line treatment changed recently?
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