Primary Resistance Mechanisms of ALK TKIs

NCT07045610 | Not Yet Recruiting

• 2 other identifiers: 202504068RINBTSTS
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

lung cancer; Anaplastic lymphoma kinase (ALK) gene rearrangement; gene mutation; Primary resistance; Next-generation sequencing; Target therapy

Outcome Measures

Primary Outcomes (1)

• resistance mechanism

  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 NGS 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.

  From ALK TKI treatment to primary resistance or rapid progression for less than 6 months.

Study Arms (1)

Patients who develop primary resistance or rapid progression after using ALK TKI.

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.

Diagnostic Test: re-biopsy tumor with primary ALK tKI resistance for NGS

Interventions

re-biopsy tumor with primary ALK tKI resistance for NGS DIAGNOSTIC_TEST

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.

Patients who develop primary resistance or rapid progression after using ALK TKI.

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

ALK-positive advanced NSCLC patients who develop primary resistance or rapid progression (within 3-6 months) during ALK inhibitor treatment.

You may qualify if:

• Age ≥ 18 years old.
• Histologically or cytologically diagnosed NSCLC
• ALK gene fusion detected at initial diagnosis of NSCLC
• Patients exhibiting primary resistance to ALK-TKI therapy, defined as the absence of initial response or progression within 3 to 6 months of treatment initiation, were included.
• Able and willing to provide written informed consent prior to performing any study related procedures and to comply with the study protocol.

You may not qualify if:

• Unable to provide written inform consent
• The patients had received other systemic treatments except ALK TKI.
• Unable to undergo tumor biopsy or venipuncture

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 10099, Taiwan

Location

Related Publications (10)

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Biospecimen

Retention: SAMPLES WITH DNA

The residual lung cancer specimens will be reserved for future lung cancer research and authorize the National Taiwan University Hospital Research Ethics Committee to review whether your consent needs to be re-obtained. The biological specimens will be encoded with a unique number and stored under the control of the National Taiwan University Hospital Ethics Committee in Laboratory 716 on the 7th floor of the National Taiwan University Hospital Research Building for a maximum of 20 years.

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chin-Shing Chen, Professor

  Taiwan Society of Thoracic Surgeons

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shang-Gin Wu, Attending Physician

CONTACT

+886223562905; b8501091@gmail.com

Chin-Shing Chen, Professor

CONTACT

+8860223123456; chenjs@ntu.edu.tw

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Surgeon, Principal Investigator, Professor

Study Record Dates

• First Submitted: June 12, 2025
• First Posted: July 1, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)