Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational [Patient Registry]
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07122882
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Chang Gung Memorial Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	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

Arms & Interventions

Arms

: Cohort 1

Oncogene-driven NSCLC with acquired resistance to tyrosine kinase inhibitor

Interventions

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

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

[email protected]

+886953094232

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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