IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER

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.

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.