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Primary Resistance Mechanisms of ALK TKIs

NCT07045610 · Status: NOT_YET_RECRUITING · Type: OBSERVATIONAL · Enrollment: 20

Last updated 2025-07-01

No results posted yet for this study

Summary

Anaplastic lymphoma kinase (ALK) gene rearrangement is a known oncogenic driver in non-small cell lung cancer (NSCLC). ALK tyrosine kinase inhibitors (TKIs) have been clearly shown to produce excellent therapeutic effects and prolong survival in patients with this gene mutation. According to current treatment guidelines, ALK inhibitors are the first-line treatment of choice for ALK-positive advanced NSCLC patients. However, although ALK TKIs are very effective, there is still a small group of patients who do not achieve good treatment outcomes, developing resistance and tumor progression within 3 to 6 months of initial ALK TKI use. This is called primary resistance. Intrinsic resistance to ALK inhibition occurs when the best clinical response after first-generation and second/third-generation TKI treatment is disease progression. Approximately 5-7% of cases after crizotinib treatment, 9% after ceritinib treatment, and 25% after lorlatinib treatment show no response to treatment, and no specific ALK mutation has been found to explain the occurrence of primary resistance. Currently, many different resistance mechanisms are known, some of which are still ALK-related, while others are ALK-independent alternative survival pathways. However, most research focuses on acquired resistance, with very few studies on primary resistance, only a few case reports. Therefore, this study aims to explore the primary ALK TKI resistance mechanisms.

The investigators plan to explore the incidence and mechanisms of primary ALK TKI resistance in ALK-positive advanced NSCLC patients who develop primary resistance or rapid progression (within 3-6 months) during ALK inhibitor treatment by re-obtaining tumor samples for genetic analysis.

Conditions

  • ALK-positive Advanced NSCLC Patients
  • Primary Resistance
  • NGS

Interventions

DIAGNOSTIC_TEST

re-biopsy tumor with primary ALK tKI resistance for NGS

Lung cancer patients who initially use ALK TKI as first-line treatment will be invited to enroll and sign the consent form. Only those who meet the criteria for primary resistance or rapid progression will proceed with tumor sample collection for genetic analysis. Alternatively, patients who develop primary resistance or rapid progression after using ALK TKI and are about to undergo tumor re-biopsy can also sign the subject consent form to be included in this study.

Sponsors & Collaborators

  • National Taiwan University Hospital

    lead OTHER

Principal Investigators

  • Chin-Shing Chen, Professor · Taiwan Society of Thoracic Surgeons

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-07-01
Primary Completion
2027-07-01
Completion
2028-07-01

Countries

  • Taiwan

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07045610 on ClinicalTrials.gov