Molecular Landscape of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients With Chinese Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
Immunotherapy has improved the prognosis of non-small cell lung cancer (NSCLC) patients, but about 80% of patients do not respond at all, which is called primary resistance. Absence of the PD-L1 expression is regarded as one of primary resistant reasons to immunotherapy, there are some other reasons which have been reported to be related with the primary resistance, including tumor mutation burden (TMB), microsatellite instability (MSI), tumor neoantigen burden (TNB), HLA genotype, loss of heterozygosity (LOH), intra tumoral heterogeneity (ITH), genome wide doubling (WGD), and ploidy. While some patients initially respond to immunotherapy, later relapse and develop disease progression, which is called acquired resistance, like escaping of interferon signaling pathways or mutations in some important genes such as B2M/JAK1/JAK2.
So the objective of this research is to explore the comprehensive immune molecular markers of primary and acquired resistance to immunotherapy in patients with Chinese advanced NSCLC based on the results of whole exome sequencing (WES) and targeted sequencing (TS)
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 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
- •Be able to provide informed consent, and understand and agree to follow the research requirements;
- •Advanced non-small cell lung cancer;
- •Patients receiving immune checkpoint inhibitor treatment represented by anti-PD-1/PD-L1 monoclonal antibody;
- •The patient must be able to provide fresh tumor tissue before- and after- ICIs (50mg of tumor tissue sample/ 2 needles of 18G thick needle puncture) or tumor tissue archived within one year (FFPE tissue block or about 15 pieces [10- 15 sheets] Freshly cut, unstained FFPE slides) and pathology reports (except for advanced non-small cell lung cancer other than neuroendocrine cancer); provide matched 10mL peripheral whole blood samples at the same time;
- •ECOG physical fitness status ≤1;
- •The patient must have at least one measurable lesion (assessed according to RECIST v1.1);
- •Life expectancy ≥ 12 weeks;
- •The patient must have adequate organ function, and must be reached absolute neutrophil count (ANC) ≥1.5x10^9/L, platelets ≥100x10^9/L, hemoglobin ≥90g/L, international normalized ratio (INR) or prothrombin time ≤ 1.5x ULN , activated partial thromboplastin time (aPTT)≤1.5x ULN, serum total bilirubin≤1.5x ULN (Patients with Gilbert syndrome can be enrolled if total bilirubin<3x ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5x ULN(Patient with liver metastases, this standard is AST and ALT≤5x ULN) within 7 days before treatment;
排除标准
- •Patients with other tumors. Except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin or cervical cancer in situ, subjects who have received potential radical treatment and have not relapsed within 5 years before the start of treatment can be included in the study;
- •Have received any approved systemic anti-tumor immunotherapy before starting the research treatment;
- •A history of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc.;
- •Severe chronic or active infections that require systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection;
- •Known human immunodeficiency virus infection; previous allogeneic stem cell transplantation or organ transplantation;
- •The investigator judged that the patient's compliance during the study period was insufficient
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to 5 years
The investigator (and the chief radiologist) used the RECIST 1.1 evaluation criteria to evaluate the efficacy indicators. CT or MRI imaging data of the chest and abdomen collected regularly during the screening/baseline period and the study period were used for tumor evaluation. Only when there may be primary or metastatic disease in the pelvis, pelvic imaging is recommended. Any other disease-affected areas (for example, the pelvis and brain) should undergo additional imaging studies based on the individual patient's signs and symptoms. If an unplanned evaluation is performed and it is shown that the patient has not progressed, follow-up evaluation should be performed at the next scheduled visit as much as possible. Scanning/tumor evaluation continued throughout the study period until RECIST 1.1 appeared
Progression-free survival (PFS)
时间窗: Up to 5 years
Calculate the time from the immunotherapy to the tumor progression/all-cause death/the end of the follow-up period.
次要结局
- Overall survival (OS)(Up to 5 years)
研究者
Xiaomin Niu
Principal Investigator
Shanghai Chest Hospital