Integrated Genomics in Oncogene-driven Non-small Cell Lung Cancer With Acquired Resistance to Tyrosine Kinase Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Genomic alterations associated with resistance to TKI
研究概览
简要总结
Currently, tyrosine kinase inhibitor (TKI) remains the standard of care for oncogene-driven non-small cell lung cancer (NSCLC). However, almost all oncogene-driven NSCLCs would develop acquired resistance against TKI in clinical practice. Therefore, understanding the molecular mechanisms underlying the acquired resistance is a critical issue in lung cancer. Based on the literature, acquired resistance mechanism against EGFR TKI includes EGFR secondary mutation (T790M, C797X, L792X, G796X, L718Q, and exon 20 insertions), MET amplification, HER2 amplification, acquired gene fusions, and other complex alterations.
From the perspective of mutagenesis, the acquired resistance against TKI may be associated with APOBEC mutational processes, kataegis, chromothripsis, extrachromosomal DNA (ecDNA), and the interaction among them. However, still 30% to 50% of oncogene-driven NSCLCs had no identified mechanism attributed to the acquired resistance. Previous studies mostly used targeted-gene sequencing, which may overlook some structural variation and the transcriptomic dynamics. This study aims to investigate the genomic alterations, mutational processes, and the transcriptomic landscape underlying the acquired resistance using integrated genomics.
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
- •Histologically confirmed NSCLC, with at least one of the known oncogene mutation prior to systemic treatment: EGFR exon 18-21 activating mutation, MET exon-14-skipping mutation, ERBB2 activating mutation, ALK fusion, ROS1 fusion, RET fusion, NTRK1 fusion, NTRK2 fusion, NTRK3 fusion, BRAF V600 mutation, or KRAS G12C mutation
- •Patient had received tyrosine kinase inhibitor (TKI) with progressive disease, as assessed by the treating physician
- •Had tumor tissue available for DNA extraction and sequencing.
- •Eligible for withdrawal of a blood sample for DNA extraction and sequencing.
排除标准
- •Patient had not received TKI or did not have documented disease progression during TKI treatment.
- •Tumor tissue was unavailable for DNA extraction or the DNA quality did not meet the sequencing requirement.
研究组 & 干预措施
Cohort 1
Oncogene-driven NSCLC with acquired resistance to tyrosine kinase inhibitor
结局指标
主要结局
Genomic alterations associated with resistance to TKI
时间窗: Through study completion, an average of 2 years
Tissue-based whole-genome and transcriptomic analysis of oncogene-driven NSCLC with acquired resistance to TKI
次要结局
未报告次要终点
研究者
Chen-Yang Huang
Principal Investigator, M.D., Ph.D.
Chang Gung Memorial Hospital