ctDNA-MRD in Stage IIIB-C NSCLC Patients Treated With Induction Chemoimmunotherapy

Study Overview
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Brief Summary
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The goal of this observational study is to explore whether ctDNA-MRD dynamic monitoring can more effectively predict the therapeutic effect of induction chemoimmunotherapy followed by surgery or non-surgical treatment for stage IIIB-C driver-negative NSCLC in the MDT model, so as to accurately guide clinical diagnosis and treatment.

Detailed Description
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This study is a single-center, observational, non-interventional, prospective study. 50 patients diagnosed with stage IIIB-C driver-negative NSCLC receiving induction chemoimmunotherapy will be planned to be enrolled in the study. Pre-treatment biopsy tissues of enrolled patients will be collected for next-generation sequencing (NGS) of institutionally-developed 1021-gene panel, and personalized detection panel will be customized based on NGS testing results. Patients will be received induction chemoimmunotherapy followed by surgery or non-surgical treatment in the MDT model and ctDNA-MRD testing will be performed at prespecified time points. For patients who received surgery following induction therapy, peripheral blood will be collected in baseline, 1 day before the third cycle of neoadjuvant therapy, 1 day before surgery, 3 days after surgery and landmark time and pulmonary venous blood will be collected intraoperatively. For patients who received non-surgical treatment following induction therapy, peripheral blood will be collected in baseline, 1 day before the third cycle of neoadjuvant therapy, 1 day before non-surgical therapy and landmark time. All included patients will be regularly followed up for at least 5 years.

Official Title
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The Role of Dynamic Circulating Tumor DNA-Molecular Residual Disease (ctDNA-MRD) Testing in Stage IIIB-C Oncogene-negative NSCLC Patients Treated With Induction Chemoimmunotherapy in the Multidisciplinary Team (MDT) Model of Diagnosis and Treatment

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Diagnostic Test: NGS and ctDNA-MRD detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathology or cytology confirmed the non-small cell lung cancer Age ranging from 18 to 75 Agree to participate in this study and sign an informed consent form Treatment-naive tumor Driver gene negativity According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is stage IIIB-C potentially resectable tumor The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score is 0-1 Exclusion Criteria: Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form Small cell lung cancer Driver gene positivity Tumor directly invades esophagus, heart, aorta, diaphragm, trachea, or carina, or is considered unresectable even following induction therapy Patients with solid organ or blood system transplantation Previous use of recombinant cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors Patients with interstitial lung disease Patients with acute or chronic infectious disease Pregnant and lactating women Patients who have undergone other clinical drug trials

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 |
| --- | --- |
| Patients with stage IIIB-C driver-negative NSCLC receiving induction chemoimmunotherapy<br> | Diagnostic Test: NGS and ctDNA-MRD detection<br>* NGS and ctDNA-MRD detection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predicting Progression Free Survival | Ability of dynamic ctDNA-MRD assessment to predict progression-free survival (PFS) in stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy followed by surgery or non-surgical therapy | up to 5 years | 
| Predicting pathologic complete response | Ability of dynamic ctDNA-MRD assessment to predict pathologic complete response (pCR) in stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy followed by surgery | Up to 1 year | 
| Predicting Overall Survival | Ability of dynamic ctDNA-MRD assessment to predict overall survival (OS) in stage IIIB-C driver-negative NSCLC patients receiving induction chemoimmunotherapy followed by surgery or non-surgical therapy | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate(ORR) | The proportion of patients achieved complete or partial remission according to RECIST 1.1 prior to definitive surgery. | Up to 1 year | 
| Adverse events (AEs) | Number of patients experiencing AEs will be recorded. An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to 5 years | 
| Perioperative complications rate | Number of patients experiencing perioperative complications will be recorded. | Up to 3 years | 
| Health-related Quality of Life | Health-related Quality of Life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0. | Up to 5 years | 
| Perioperative pain evaluation | Perioperative pain evaluation assessed by a numeric rating scale (NRS). A total of 11 points from 0 to 10 are used to describe the pain intensity. 0 means no pain, the number of points increases when the pain is stronger, and 10 means the most intense pain. | Up to 3 years | 
| Lung cancer-related Quality of Life | Health-related Quality of Life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire in Lung Cancer. | Up to 5 years |