Immune Metabolism Dysregulation and Efficacy to Anti-PD-1 PD-L1 Agents in Non Small Cell Lung Cancer Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Overall survival OS
研究概览
简要总结
Prospective, biological, observational study involving the collection and use of samples from patients suffering from NSCLC lung cancer, aimed at comparing the molecular profile related to metabolism among subjects with response or resistance to checkpoint inhibitors immune system (ICI), in order to contribute to define response biomarkers and new molecular pathways as therapeutic targets combine with ICI to overcome resistance.
详细描述
This study aims to identify the metabolic pathways related to the tumor microenvironment in NSCLC patients and their role in the response to ICI.
To this end, the metabolic picture will be evaluated on tumor-associated fibroblasts and macrophages tumor-associated and tumor-infiltrating lymphocytes, obtained from tissue samples of two different cohorts of patients candidate to receive immune-checkpoint treatment inhibitors. Furthermore it will correlate metabolic alterations in tumor tissues and peripheral immune cells or in plasma proteins of NSCLC patients with clinical response to ICIs.
For this purpose, serum/plasma and peripheral blood mononuclear cells (PBMC) will be isolated from the peripheral blood of patients to carry out phenotypic, metabolic and transcriptional studies on cells peripheral immune system. Finally it will come explored the therapeutic modulation of metabolic signatures identified in ex vivo models, using organoids and cultures of organotypic tissue sections obtained from patients affected by NSCLC, subjected to curative surgical treatment and treatment naive.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 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
- •Histological diagnosis of advanced stage NSCLC
- •Histotype adenocarcinoma and squamous carcinoma
- •ECOG PS <2
- •Known PDL-1 stage
- •Measurable disease
- •Availability of tumor tissue
- •No evidence of molecular drivers
- •Written informed consent (to the study and data processing)
- •For the second cohort in addition to the precedents it is included
- •Diagnosis of limited or locally advanced NSCLC deemed resectable
- •For the third cohort in addition to the precedents it is included
- •patients candidates for surgery for non-small cell lung cancer
排除标准
- •Contraindications to immunotherapy
- •Unavailability of tumor tissue
- •Histotype with neuroendocrine or mixed component
- •For the second cohort
- •Contraindication to immunotherapy
- •Histotype with neuroendocrine or mixed component
- •Locally advanced disease candidate for concomitant chemo-radiotherapy treatment
- •For the third cohort
- •previously treated patients
研究组 & 干预措施
Serum collection
Collection of sera/plasma from 400 patients, present in the Institute's Biobank. These are cells peripheral blood mononuclear cells (PBMC) and 150 tumor-infiltrating lymphocytes, cells immune cells that infiltrate adjacent non-tumor tissue and autologous CAFs from patients admitted to the IRE Institute for curative surgery. 20% of these patients relapse and access treatment Oncology Unit to be treated with immunotherapy according to the guidelines. This allows the availability on archive of tumor tissue, PBMC, CAF and TIL frozen at the time collected of the intervention who, at the time of progression, will begin treatment with ICIs according to clinical guidelines
Neoadjuvant treatment
Tissue taken will be collected, as per clinical practice, to curative surgery and when available to diagnostic biopsy. We plan to biobank in prospective manner: PBMC and plasma at the start of neoadjuvant treatment, the day before of surgery and during clinical follow-up with a pattern of every 3 months for at least 6 months of follow up and where possible up to 21 months. Evaluation of the response will be carried out by analysis of the pathological response in surgical tissue according to conventional criteria.
Tissue samples
Collection of fresh tissue samples from treatment-naïve patients undergoing surgery for NSCLC. Which will be prospectively biobanked, particularly PBMC and day-ahead plasma of the surgery.
结局指标
主要结局
Overall survival OS
时间窗: 24 months
The application of spatial transcriptomic approaches will enable the discovery of specific cellular niches that may be responsible for mechanisms of sensitivity or resistance to ICI. With the results you get, you will probably have a chance to locate it new and wonderful metabolic pathways capable of exerting their anti-tumor effect even in combination with ICIs.
次要结局
未报告次要终点