Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated NSCLC Patients

Study Overview
=================
Brief Summary
-----------------
To evaluate the predictive value of ctDNA in response, relapse for patients treated with immune checkpoint inhibitors or targeted therapy for ALK, ROS1, MET ex14 skipping.

Detailed Description
-----------------
In the study, 250 advanced NSCLC patients will be recruited. All the patients will receive tissue biopsy and circultating tumor DNA (ctDNA) liquid biopsy before entry the study. Patients who have no actionable mutations in EGFR or ALK and receive ICIs treatment and patients who carry actionable ROS1 fusion, ALK fusion or MET exon 14 skipping mutation and receive TKI treatment according to guidelines will take liquid biopsy assay to monitor the mutation status. The study will be ended when over 70% of the patients had a progressive disease (PD) in their targeted lesion.

Official Title
-----------------
Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients Treated With Immune Checkpoint Inhibitors (ICIs) or Targeted Therapy

Conditions
-----------------
Lung Neoplasms, Lung Cancer, Nonsmall Cell, Adenocarcinoma of Lung, Squamous Cell Lung Cancer

Intervention / Treatment
-----------------
* Other: Observation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of informed consent Newly diagnosed and histological or cytological confirmed stage IIIB-IV lung adenocarcinoma or squamous cell carcinoma patients according to the AJCC staging system. The stage IV lung cancer and brain metastasis can be diagnosed by imaging and enhanced CT respectively No EGFR mutation in tissue and ctDNA Received immune checkpoint inhibitors as the first line therapy ECOG performance status 0-2 with expected more than 6 months of survival time Willingness to comply with required protocols and give permission to use the data for clinical research and products development Exclusion Criteria: Patients have other primary cancers Patients have symptomatic brain metastasis, complications that are associated with brain metastasis or cognitive disorders Patients failed in either plasma or tissue sample QC

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Immune checkpoint inhibitors<br> | Other: Observation<br>* observe the association of ctDNA with efficacy of treatment<br>|
| Targeted therapy<br>Targeting ALK, ROS1, MET ex14 skipping | Other: Observation<br>* observe the association of ctDNA with efficacy of treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the evolution of ctDNA mutation profile during treatment | ctDNA mutation will be detected, PyClone based clonal analysis will be performed to analyze the clonal dominance | every 2-3 cycles of treatment upon physicians' request, ctDNA mutation analysis and clonal analysis (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resistant mechanisms of targeted therapy | Resistant mutations will be identified from ctDNA or tissue mutations | At the time of disease progression (through study completion, an average of 1.5 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Next Generation Sequencing (NGS), Liquid biopsy, Immune Checkpoint Inhibitor, Whole Transcriptome Sequencing