DETERMINANTS OF IMMUNOTHERAPY EFFICACY IN ENDOMETRIAL CANCER

NCT07690540 | Recruiting

• 2 other identifiers: UID 5328L2-593
• Study Type: interventional
• Target: 510
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, the introduction of immune checkpoint inhibitors (ICI) in combination with chemotherapy has significantly changed the management of advanced and recurrent Endometrial Cancer (EC). Despite these advances, responses to immunotherapy remain heterogeneous. Not all patients with mismatch repair-deficient (dMMR) tumors derive durable benefit, while a subset of mismatch repair-proficient (pMMR) tumors may respond. In addition, ICI treatment is associated with relevant costs and immune-related toxicities, highlighting the need for improved patient selection. To date, no validated predictive biomarkers beyond mismatch repair (MMR) status are available, reflecting limited understanding of the biological mechanisms underlying sensitivity and resistance to immunotherapy in EC. This study aims to assess and integrate molecular and epigenetic features to identify prognostic and predictive biomarkers of immunotherapy response in endometrial cancer, and to explore their functional relevance using patient-derived experimental models.

Conditions

Endometrial Cancer; Immune Checkpoint Inhibitors

Keywords

endometrial cancer; immune checkpoint inhibitors; biomarkers; target therapy; translational research

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival

  Time from enrollment to first disease progression or death from any cause, whichever occurs first

  2 years

• Overall Survival

  Time from enrollment to death from any cause

  2 years

Study Arms (1)

Prospective Exploratory Cohort

EXPERIMENTAL

Genomic, epigenomic, transcriptomic, proteomic, and lipidomic analyses

Biological: Prospective exploratory cohort

Interventions

Prospective exploratory cohort BIOLOGICAL

Fresh tumor samples, paired with FFPE tissue, will be collected prior to initiation of immunotherapy and will be used to generate patient-derived three-dimensional tumoroids on a microfluidic organ-on-chip platform.

Prospective Exploratory Cohort

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically confirmed advanced or recurrent endometrial carcinoma or carcinosarcoma
• No prior treatment with immune checkpoint inhibitors
• Availability of paired fresh-frozen and FFPE tumor samples
• Provision of written informed consent for participation in translational research

You may not qualify if:

• Refusal or inability to provide informed consent by the patient or legal representative
• Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian cancer)
• Active treatment with immunomodulatory agents at the time of sample collection (e.g., immunotherapy for autoimmune disease)
• Known positivity for HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)

Sponsors & Collaborators

• European Institute of Oncology: lead
• Mario Negri Gynecologic Oncology group (MaNGO): collaborator

Study Sites (1)

European Institute of Oncology

Milan, Italy, 20141, Italy

RECRUITING

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

Study Officials

• Ilaria Betella

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ilaria Betella, MD

CONTACT

+390257489431; ilaria.betella@ieo.it

Study Design

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

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 8, 2026
• Study Start: April 14, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: July 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

IT (1)