Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

NCT ID: NCT07122882

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-05-11

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.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cohort 1

Oncogene-driven NSCLC with acquired resistance to tyrosine kinase inhibitor

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chen-Yang Huang

Principal Investigator, M.D., Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Chen-Yang Huang, M.D., Ph.D.

Role: CONTACT

cyhuang1985@cgmh.org.tw

+886953094232

Other Identifiers

202500569B0

Identifier Type: -

Identifier Source: org_study_id