Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

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

Status

Enrolling by invitation

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT07122882

Enrollment

Registered

2025-08-14

Start date

2025-09-01

Completion date

2028-05-11

Last updated

2026-03-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ALK Fusion-positive Solid or CNS Tumors, BRAF V600 Mutation, 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, Oncogene-addicted Non Small Cell Lung Cancer, RET Fusion Positive, ROS1 Fusion Positive

Keywords

oncogene-driven NSCLC, acquired resistance, integrated genomics

Brief summary

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. 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 2. Patient had received tyrosine kinase inhibitor (TKI) with progressive disease, as assessed by the treating physician 3. Had tumor tissue available for DNA extraction and sequencing. 4. Eligible for withdrawal of a blood sample for DNA extraction and sequencing.

Exclusion criteria

1. Patient had not received TKI or did not have documented disease progression during TKI treatment. 2. Tumor tissue was unavailable for DNA extraction or the DNA quality did not meet the sequencing requirement.

Design outcomes

Primary

Measure	Time frame	Description
Genomic alterations associated with resistance to TKI	Through study completion, an average of 2 years	Tissue-based whole-genome and transcriptomic analysis of oncogene-driven NSCLC with acquired resistance to TKI

Countries

Taiwan

Outcome results