Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

NCT07122882 | Enrolling By Invitation

• 1 other identifier: 202500569B0
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

oncogene-driven NSCLC; acquired resistance; integrated genomics

Outcome Measures

Primary Outcomes (1)

• Genomic alterations associated with resistance to TKI

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

  Through study completion, an average of 2 years

Study Arms (1)

Cohort 1

Oncogene-driven NSCLC with acquired resistance to tyrosine kinase inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who have histologically confirmed NSCLC, with at least one of the known oncogene mutation at baseline (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), and have documented disease progression during TKI treatment.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital Linkou Branch

Taoyuan District, 333, Taiwan

Location

Biospecimen

Retention: SAMPLES WITH DNA

Solid tumor tissue sample, peripheral blood sample

MeSH Terms

Conditions

Central Nervous System Neoplasms

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, M.D., Ph.D.

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 14, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): May 11, 2027
• Study Completion (Estimated): May 11, 2028
• Last Updated: March 17, 2026

Record last verified: 2025-08

Locations

TW (1)