Predicting Response to Anti-PD-1/PD-L1 Immunotherapy by Plasma Extracellular Vesicle Analysis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 378
- 试验地点
- 5
- 主要终点
- Target protein levels in plasma-derived extracellular vesicles (EVs) measured by multiplex ELISA before treatment
研究概览
简要总结
The objective of this prospective multicenter study is to evaluate whether the analysis of immunological biomarkers present in circulating extracellular vesicles is associated with the response to anti-PD-1/PD-L1 treatments in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or unresectable melanoma.
Patients will receive standard-of-care treatment and will be followed according to routine clinical practice. The study involves the collection of four study-specific blood samples at different time points during follow-up, as well as the collection of standard immunohistochemistry results, thoraco-abdomino-pelvic CT scans, and tumor DNA genotyping analyses performed as part of routine care.
The study aims to determine:
- whether baseline biomarkers in extracellular vesicles are associated with response to anti-PD-1/PD-L1 treatment,
- how these biomarkers change over the course of treatment, and
- to provide exploratory data for the development of predictive immunological response signatures.
详细描述
Immune checkpoint inhibitors (anti-PD-1/PD-L1) have become standard treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) or melanoma. However, not all patients respond to these therapies, and current biomarkers are imperfect.
Circulating extracellular vesicles (EVs) are nanovesicles derived from tumor and immune cells, carrying proteins, nucleic acids, and lipids. They represent an accessible and stable source of immunological biomarkers, allowing monitoring of the tumor microenvironment without additional invasive procedures.
This prospective multicenter study aims to:
- Collect and analyze immunological biomarkers present in EVs at baseline and during follow-up.
- Assess their association with objective response to anti-PD-1/PD-L1 treatment, measured according to RECIST 1.1.
- Develop an exploratory composite score combining multiple markers to predict response, stratified by cancer type (NSCLC vs melanoma).
- Prospectively collect biological samples for future exploratory analyses.
Study procedures for participants include:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) or locally advanced/metastatic unresectable melanoma.
- •Patient scheduled to initiate anti-PD-(L)1 therapy, either as monotherapy or in combination (other immune checkpoint inhibitors, chemotherapy, etc.).
- •Baseline tumor assessment performed within 28 days prior to enrollment (CT scan of thorax, abdomen, and pelvis) with at least one measurable lesion according to RECIST 1.1 criteria.
- •Life expectancy >6 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at enrollment.
- •Patient able to provide informed consent and comply with study procedures.
- •Patient covered by a social security system or equivalent.
排除标准
- •Prior treatment with immunotherapy.
- •Presence of EGFR or ALK mutation (applicable only to the lung cohort).
- •Presence of another synchronous malignancy.
- •Diagnosis of uveal melanoma.
- •Treatment with systemic immunosuppressants, including within 28 days prior to enrollment, or corticosteroids >10 mg/day, including within 14 days prior to enrollment.
- •Disease not measurable according to RECIST 1.1 criteria.
- •Positive serology for HIV, HBV, or HCV.
- •Pregnant or breastfeeding women.
- •Inability to comply with study follow-up and visits for geographic, social, or psychological reasons.
- •Individuals deprived of liberty or under legal guardianship (including curatorship).
研究组 & 干预措施
Advanced NSCLC or Melanoma - Anti-PD-(L)1 Therapy
This cohort includes patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or inoperable melanoma who are receiving standard-of-care anti-PD-1 or anti-PD-L1 therapy, either as monotherapy or in combination with other approved therapies.
Participants will follow standard clinical management, and study-specific procedures include four blood draws for extracellular vesicle (EV) analysis at baseline and during follow-up, collection of standard immunohistochemistry results (PD-1, PD-L1, CTLA-4, Tim-3, LAG-3, TIGIT), thoraco-abdominopelvic CT imaging, and tumor DNA genotyping performed as part of routine care.
结局指标
主要结局
Target protein levels in plasma-derived extracellular vesicles (EVs) measured by multiplex ELISA before treatment
时间窗: 6 months from treatment initiation
Treatment response assessed as Best Overall Response (BOR: complete or partial response per RECIST 1.1) within 6 months.
次要结局
未报告次要终点