ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLC

Study Overview
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Brief Summary
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This study aims to explore the correlation of circulating tumor DNA(ctDNA) and the risk of progression in patients with advanced NSCLC who have long-term benefit from first-line immunotherapy (PFS 12 months)

Detailed Description
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Evidence suggests that circulating tumor DNA (ctDNA) analysis can noninvasively identify minimal residual disease (MRD) in clinical oncology. The researches will be sharply increased about ctDNA potential clinical application in the near future. In the early stage of NSCLC, ctDNA has been indicated to identify those at high risk of recurrence after radical surgery. And this study will focus on those patients with advanced NSCLC who have long-term benefit from first-line immunotherapy (PFS 12 months). 10ml plasma will be collected every three months until disease progression to interrogate ctDNA by high-depth panel sequencing, exploring its prediction value about the risk of progression. Meanwhile, the investigators would like to explore the lead time of detectable ctDNA before regular imaging finding.

Official Title
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A Multicenter, Prospective Clinical Study of Circulating Tumor DNA Analysis to Monitor the Risk of Progression After Long-term Benefit to First-line Immunotherapy in Patients With Advanced NSCLC

Conditions
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Advanced Lung Non-Small Cell Carcinoma

Intervention / Treatment
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* Diagnostic Test: ctDNA detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 75 years old Advanced non-small cell lung cancer (stage IIIB-IV), pathological types limited to squamous cell carcinoma or adenocarcinoma, driver gene mutations (EGFR/ALK/ROS1) were negative General condition: ECOG score 0 or 1 First-line monotherapy or combination immunotherapy The long-term benefit of immunotherapy was defined as PFS=12months Tumor tissue samples can be obtained at the time of enrollment, and at least 5   10 sections can be generated, and the pathological report indicates that the overall tumor content is not less than 10%. At least one measurable lesion (except patients with CR after first-line treatment) can be evaluated according to RECIST1.1 standard. Have self-awareness, be able to understand the research scheme and voluntarily participate in the study, and can sign the informed consent form Have good compliance, be able to cooperate with the collection of specimens from each node and provide corresponding clinical information. Exclusion Criteria: Serious primary diseases of the heart, liver and kidney Other malignant tumors within 3 years prior to diagnosis of NSCLC Women in pregnancy and lactation The active stage of human immunodeficiency virus (HIV) infection Patients with active systemic infection, pneumonia, tuberculosis, pericarditis Patients who cannot understand the content of the experiment and cannot cooperate and refuse to sign informed consent.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Advanced NSCLC patients with long-term benefit after first-line immunotherapy<br>For patients with advanced NSCLC who have long-term benefit (PFS 12 months) after first-line immunotherapy | Diagnostic Test: ctDNA detection<br>* High-depth sequencing method is used to detecting ctDNA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Time from the beginning of first-line immunotherapy to the first progression(PD) in patients with advanced NSCLC. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The correlation of ctDNA and risk of progression | The correlation of ctDNA and risk of progression during the erolled observation process | 3 years | 
| Lead time | Lead time defined as the interval between ctDNA detection and imaging of progression. | 3 years | 
| Incidence of adverse events | the incidence of adverse events during the whole observation time | 3 years | 
| Overall survival (OS) | Overall survival (OS) defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ctDNA, advanced lung cancer, first-line immunotherapy, the risk of progression, minimal residual disease (MRD), long-term benefit