Endometrial Cancer, Immune Checkpoint Inhibitors
Conditions
Keywords
endometrial cancer, immune checkpoint inhibitors, biomarkers, target therapy, translational research
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.
Interventions
BIOLOGICALProspective exploratory cohort
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.
Sponsors
European Institute of Oncology
Mario Negri Gynecologic Oncology group (MaNGO)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | 2 years | Time from enrollment to first disease progression or death from any cause, whichever occurs first |
| Overall Survival | 2 years | Time from enrollment to death from any cause |
Countries
Italy
Contacts
CONTACTIlaria Betella, MD
PRINCIPAL_INVESTIGATORIlaria Betella
European Institute of Oncology
Outcome results
None listed