NGS-based Comprehensive Genomic ctDNA Panel in NSCLC With Immunotherapy

Study Overview
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Brief Summary
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Liquid biopsy based on next-generation sequencing (NGS) method has become an increasingly powerful detection tool for clinical research and practice. As a companion diagnostic panel, circulating tumor DNA (ctDNA) assay has the considerable potential to detect the blood tumor mutation burden (bTMB), and bTMB calculated by ctDNA assay is regarded as a novel and promising biomarker for immunotherapy nowadays. Though immune checkpoint inhibitors (ICIs) in immunotherapy are highly effective but can induce severe immune-related adverse events (irAEs), which cannot be better predicted in advance. Meanwhile adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based immunotherapy. This research is to characterize in-depth TCRs derived from HLA-mismatched allogeneic repertoire targeting different myeloperoxidase (MPO)-derived peptides presented by the same HLA-restriction element. Overall the purpose of this trial is to investigate the combined predictive biomarkers (including bTMB and HLA) related to the immunotherapy effects and the biomarker (TCR) associated with adverse reactions during immunotherapy and hold a predictive role, thus further benefit patients receiving immunotherapy, especially in the advanced stage lung cancer patients where tissue samples are unavailable.

Detailed Description
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Blood samples including the plasma and PBMC (peripheral blood mononuclear cell) from immunotherapy-naive lung cancer patients will be analyzed by CGP panel (OrigiMed, Inc.) for multiple molecular biomarkers including mutations with sensitivity/resistance to targeted therapies, bTMB, HLA, etc. Treatment methods and outcomes will be followed-up to inspect the clinical benefit and safety with CGP-panel analysis.

Official Title
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A Prospective Study on NGS-based Comprehensive Genomic ctDNA Panel in NSCLC Treated With Immunotherapy

Conditions
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Lung Cancer

Intervention / Treatment
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* Other: The method of gene mutation detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant aged 18 or above, and gender unrestricted Individual with pathologically diagnosed lung cancer Exclusion Criteria: Patients with concomitant other tumors Individual with severe cardiopulmonary insufficiency and hypoproteinemia Women who were pregnant and were during their lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

| Intervention/Treatment |
| --- |
|Other: The method of gene mutation detection|All samples were detected by NGS CGP panel.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS will be defined as the time from initial treatment to the time of disease progression or death | through the whole study period, an average of 3 years | 
| Blood Tumor Mutational Burden (bTMB) | bTMB will be defined as the total number of detected somatic mutation counts in coding regions per million bases in plasma ctDNA | halfway of the study, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other biomarkers | The distribution and clinical applications including benefit and adverse reaction of biomarkers such as HLA, TCR and gene mutations in Chinese non-small cell lung cancer patients | halfway of the study, an average of 1 year | 
| Clonality | The tumor clonality in Chinese non-small cell lung cancer | halfway of the study, an average of 1 year | 
| Overall survival (OS) | OS will be defined as the time from cancer diagnosed time to the time of death | through the whole study period, an average of 3 years |