Multi-Omics Testing for Immunotherapy Efficacy Evaluation (MOTIVATION)

Study Overview
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Brief Summary
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This multicenter prospective observational and exploratory study aims to develop and validate a novel multi-omics-based computational method for neoantigen prediction in non-small cell lung cancer (NSCLC), and discover biomarkers for evaluation of PD-1/PD-L1 inhibitor's efficacy in patients of advanced NSCLC.

Detailed Description
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Tumor tissues and blood samples from about 400 patients with non-small-cell lung cancer (NSCLC) will be collected for the study, which will be subject to NGS-based genomic, transcriptomic, and methylomic profiling in order to construct a multi-omics landscape of NSCLC. These multi-omics data will be used to construct and validate a novel computational method for neoantigen prediction. Additionally, biomarkers will be explored for prognosis and patient stratification, as well as for evaluation of PD-1/PD-L1 inhibitor treatment efficacy in patients of advanced NSCLC.

Official Title
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A Multicenter Prospective Observational Study of Non-small Cell Lung Cancer Patients for Development and Validation of Computational Method for Multi-omics-based Neoantigen Prediction and Biomarkers for Immunotherapy Response Evaluation

Conditions
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Non-small Cell Lung Cancer, Neoantigen, Next-generation Sequencing, Biomarker

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stage I-IV non-small cell lung cancer(with no restriction of age, gender, or smoking history) Patients in the group will be allowed to collect whole blood and tissue samples at specific time points Eastern Cooperative Oncology Group Performance Status of 0-1 within 28 days prior to registration No previous systemic anti-tumor therapy Signed informed consent Exclusion Criteria: Active or history of autoimmune disease or immune deficiency Patients with serious mental disease Prior allogeneic stem cell or solid organ transplantation Pregnant or lactating women Patients who cannot obtain tumor tissue samples and / or whole blood Patients with history of blood transfusion within half a year Patients with any other malignancy diagnosed within 5 years Received systemic anti-tumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Progression free survival (PFS) is defined as the period a participant remains alive without disease progression after study registration. Tumor status is assessed per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) by computed tomography (CT), positron emission tomography (PET) CT and/or X rays. Complete Response (CR) = Disappearance of all lesions Partial Response (PR) = ≥30% decrease in the sum of the lesion diameters Overall Response (OR) = CR + PR Progressive disease (PD) = 20% increase in the sum of lesion diameters, and/or the appearance of 1+ new lesion(s) Stable disease (SD) = Small changes that do not meet any of the above criteria | 2 years | 
| Disease-free survival (DFS) | Disease-free survival (DFS) is defined as the number of participants remaining alive without disease progression (PD), symptomatic deterioration or death due to any cause. DFS is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as follows. Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions Progressive disease (PD) = 20% increase in the sum of the diameters of target lesions (must be > 5 mm), unequivocal progression of non-target lesions, and/or the appearance of one or more new lesion(s) Stable disease (SD) = Small changes that do not meet any of the above criteria. The outcome will be reported as the number of participants who meet the criteria for DFS, a number without dispersion. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival (OS) defined as the duration from study registration until death due to any cause. The outcome will be reported as the number of participants known to be alive at 24 months after study registration, a number without dispersion. | 2 years |