IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER

NCT07374809 | Not Yet Recruiting

• 2 other identifiers: UID 5032L2-516
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Endometrial Carcinoma (EC); pMMR; DMMR Cancer

Outcome Measures

Primary Outcomes (1)

• predictive biomarkers

  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

Study Arms (1)

arm 1

EXPERIMENTAL

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

Interventions

DNA methylation profiles DIAGNOSTIC_TEST

MAP mutations, DNA methylation profiles, transcriptome, TME composition, and lipid abundance of tumor samples from EC patients that underwent immunotherapy;

arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

Istituto Europeo di Oncologa

Milan, Lombardy, 20141, Italy

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Ilaria Betella, MD, MD

CONTACT

00390257489431; ilaria.betella@ieo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2026
• First Posted: January 29, 2026
• Study Start: January 21, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: January 29, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)