IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER (DEMETER)

January 21, 2026 updated by: European Institute of Oncology

DISSECTING THE EPIGENOME AND MICROENVIRONMENT TO UNDERSTAND IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER (DEMETER PROJECT)

Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%.

Recently, four phase III studies (RUBY, NRG-GY018, AtTEnd, and DUO-E) have demonstrated that the addition of anti-PD-1/PD-L1 immunotherapy to first-line chemotherapy significantly improves progression-free survival, particularly in tumors with altered DNA repair mechanisms known as mismatch repair (MMR) (so-called mismatch repair-deficient or dMMR tumors), but with benefits also observed in a subset of tumors with normal MMR function (so-called MMR-proficient or pMMR tumors). However, despite the clinical approval of these therapies, reliable biomarkers capable of predicting response to immunotherapy are still lacking.

This project aims to comprehensively characterize the genomic, epigenetic, and lipid properties of the tumor and the tumor microenvironment (TME) in order to identify predictive markers of response to immunotherapy, thereby laying the foundation for a personalized therapeutic approach in endometrial carcinoma.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary objective To identify and validate predictive biomarkers of response to immunotherapy in dMMR and pMMR endometrial carcinomas through an integrated multi-omics approach (genomic, epigenomic, transcriptomic, and lipidomic) and functional validation in patient-derived models.

Population characteristics Patients with advanced (stage III-IV) or recurrent epithelial endometrial carcinoma, treated with anti-PD-1/PD-L1 immunotherapy in combination with or following standard platinum-based chemotherapy at the European Institute of Oncology.

Inclusion criteria:

Advanced or recurrent endometrial carcinoma patients undergoing biopsy or cytoreductive surgery followed by immunotherapy

Age ≥ 18 years

Fresh tumor tissue available at the IEO Biobank

Written informed consent

Exclusion criteria:

Mesenchymal tumors

Carcinomas of non-endometrial origin

Chronic viral infections (HIV, HBV, HCV)

Number of patients and main criteria

  • Total number of planned patients: 50
  • Number of IEO patients: 50
  • Competitive: No
  • Special population: Rare disease / advanced tumor
  • Sex and menopausal status: Female, pre- or post-menopausal
  • Disease stage: III-IV (advanced or recurrent)
  • Main subtypes: dMMR and pMMR; molecular subgroups (POLE, p53, NSMP) when available

Duration (in months)

  • Enrollment duration: 18
  • Follow-up duration: 12 (calculated from the last patient enrolled)

Rationale: with approximately 150 new EC cases per year at IEO (about 20% advanced/recurrent), enrolling 50 patients over 18 months is realistic; a 12-month follow-up allows for clinical evaluations (response/early PFS) that are useful for multi-omics analyses and validation.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Lombardy
      • Milan, Lombardy, Italy, 20141
        • Istituto Europeo di Oncologa
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female patients ≥ 18 years old.
  • Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed, or carcinosarcoma).
  • Advanced (stage III-IV) or recurrent disease, eligible for surgery or biopsy as part of the therapeutic plan.
  • Availability of fresh-frozen or OCT-embedded tumor tissue obtained at surgery/biopsy and stored in the IEO Biobank.
  • Mismatch-repair-deficient (dMMR) or -proficient (pMMR) molecular subtype (when available).
  • Written informed consent for participation and use of biological material for translational research purposes.

Exclusion Criteria:

  • Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian, cervical).
  • Prior systemic treatment with immune checkpoint inhibitors for other malignancies.
  • Insufficient or poor-quality tumor tissue available for molecular analyses.
  • Active or uncontrolled infection with HIV, HBV, or HCV.
  • Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: arm 1
Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed histology, or carcinosarcoma), classified as dMMR or pMMR -Availability of a fresh tumor sample suitable for study procedures
Diagnostic test: DNA methylation profiles
MAP mutations, DNA methylation profiles, transcriptome, TME composition, and lipid abundance of tumor samples from EC patients that underwent immunotherapy;

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
predictive biomarkers
Time Frame: 2 years
To identify and validate predictive biomarkers of response to immunotherapy in dMMR and pMMR endometrial carcinomas through an integrated multi-omics approach (genomic, epigenomic, transcriptomic, and lipidomic) and functional validation in patient-derived models.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Institute of Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 21, 2026

Primary Completion (Estimated)

November 30, 2027

Study Completion (Estimated)

November 30, 2027

Study Registration Dates

First Submitted

January 21, 2026

First Submitted That Met QC Criteria

January 21, 2026

First Posted (Actual)

January 29, 2026

Study Record Updates

Last Update Posted (Actual)

January 29, 2026

Last Update Submitted That Met QC Criteria

January 21, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UID 5032
  • L2-516 (Other Identifier: Comitato Etico Territoriale Lombardia 2)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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