Plasma Molecular Profiling in ALK Inhibitor Resistant NSCLC

Study Overview
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Brief Summary
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The investigators plan to understand a comprehensive molecular profiling via the plasma, with the primary aim of using this form on analysis to guide subsequent treatment selection. This study will provide a better understanding of ALK resistance in the treatment of Asian lung cancers and allow for improved clinical outcomes by 'matching' the secondary mutations to an ALK inhibitor which would allow for the greatest coverage ultimately leading to lasting duration of response.

Official Title
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Plasma Molecular Profiling in ALK Inhibitor Resistant Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer, ALK-Positive Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced ALK fusion oncogene positive lung adenocarcinoma that have progressed after 1-2 ALK inhibitors, with at least one prior line of 2nd generation ALKi (i.e. Ceritinib, Alectinib, Brigatinib or Ensartinib) The availability of sufficient plasma Age ≥ 21 years WHO performance status ≤ 2 Life expectancy of ≥ 21 weeks Patients should have adequate organ function for potential consideration into clinical trials (routine blood tests are valid within 14 days before enrollment): Adequate bone marrow function as shown by: ANC ≥ 1.0x10^9/L, Platelets ≥ 75x10^9/L, Hb ≥ 7.5 g/dL Alanine aminotransferase (ALT) and aspirate aminotransferase (AST) normal range (or ≤ 3.0xULN if liver metastases are present) Willing to provide signed informed consent Patients whom do not fulfill the above criteria may be discussed on a case-by-case basis within the study team, for potential enrolment Exclusion Criteria: Received more than 2 prior ALK inhibitors (ALKi) Symptomatic or uncontrolled brain metastases requiring concurrent treatment inclusive but not limited to surgery and radiation. Stable/ tailing doses of corticosteroids is permitted

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prior 2nd generation ALKi<br> | |
| Prior 1st and 2nd generation ALKi<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular profiling of plasma | Profiling of the collected plasma samples at a molecular level to evaluate the molecular epidemiology of ALK fusion oncogene positive lung cancer | 2 to 4 weeks after collection of plasma | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient survival status |  | After molecular profiling has been completed, every few months up to 2 years | 
| Subsequent patient treatment status |  | After molecular profiling has been completed, every few months up to 2 years | 
| Clinical outcomes of the subsequent treatments the patients receive |  | After molecular profiling has been completed, every few months up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALK inhibitor (ALKi), NSCLC, Anaplastic lymphoma kinase (ALK) fusion oncogene NSCLC, Guardant360 assay, Next-Generation Sequencing (NGS) DNA sequencing test, Cell-free circulating tumor DNA (ctDNA), Plasma profiling, Blood-based assay, Mutational testing, 74 genetic alterations (point mutations, copy number variants, fusions, insertions, deletions), ALK resistance mutations