DISSECTING THE EPIGENOME AND MICROENVIRONMENT TO UNDERSTAND IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER (DEMETER PROJECT)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- predictive biomarkers
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: DNA methylation profiles (Diagnostic Test)
结局指标
主要结局
predictive biomarkers
时间窗: 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.
次要结局
未报告次要终点