Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

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.

Enrolling by Invitation

Interested in participating?

Request Info

Key information

Conditions

Oncogene-addicted Non Small Cell Lung Cancer ALK Fusion-positive Solid or CNS Tumors BRAF V600 Mutation Central Nervous System Neoplasms EGFR Mutation ERBB2 Mutation-Related Tumors KRAS G12C Mutation MET Exon 14 Skipping Mutation NRG1 Fusion NTRK1 Fusion Positive NTRK2 Fusion Positive NTRK3 Fusion Positive Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms RET Fusion Positive ROS1 Fusion Positive

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Chang Gung Memorial Hospital Linkou Branch

Taoyuan, 333, Taiwan

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

Primary outcomes

Genomic alterations associated with resistance to TKI

Time frame: Through study completion, an average of 2 years

Tissue-based whole-genome and transcriptomic analysis of oncogene-driven NSCLC with acquired resistance to TKI

Sponsors and collaborators

Lead sponsor

Chang Gung Memorial Hospital

Other

Registry information

Official study title

Integrated Genomics in Oncogene-driven Non-small Cell Lung Cancer With Acquired Resistance to Tyrosine Kinase Inhibitors

Important dates

Study start: 2025
Primary completion: 2027
Study completion: 2028
First posted: Aug 14, 2025
Registry last updated: Mar 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Recruiting