PDL-1 Expression on Circulating Tumor Cells in Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Immunotherapy is probably, since the development of therapies targeting EGFR mutations or ALK rearrangement, the most attractive therapeutic perspective in the management of metastatic lung cancer. Among the compounds tested, the inhibitors of the immune checkpoint PROGRAMME DEATH 1 / PROGRAMME DEATH LIGAND 1 (PD-1/PD-L1) have been tested in numerous clinical trials with recently published positive results leading to the approval of one drug in the USA and an expanded access program for two drugs in France. PROGRAMME DEATH LIGAND 1 (PD-L1) expression by tumor cells is strongly associated with the response to such molecules so that the participation in various clinical trials is currently reserved for patients expressing this biomarker and therefore justifies a new invasive biopsy (bronchoscopic or CT-guided) representing a considerable drag on the access to these treatments. Circulating tumor cells (CTCs) isolated by Isolation by Size of Tumor Cells (ISET) offer a direct and non-invasive access to the tumor. It has already been demonstrated that molecular characterization (EGFR, ALK) on these blood samples is possible. We propose to demonstrate the feasibility of the analysis PDL-1 expression in these cells by immunocytochemistry. Myeloid-Derived Suppressor Cells (MDSCs) are immature myeloid cells that inhibit T cell functions and thus promote tumor growth. These cells frequently express PD-L1. We propose to test whether MDSCs level and its evolution during treatment with PD1 inhibitor is correlated to the response to these drugs. The main objective of this study is to demonstrate the feasibility of the analysis of PD-L1 expression on CTC

Official Title
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Feasibility Study of PD-L1 Expression Analysis on Circulating Tumor Cells by Immunocytochemistry and MDSCs Level Evolution Analysis in Non-small Cell Lung Cancer Treated With PD-L1 or PD1 Inhibitor

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: blood sample collection for CTC and MDSC analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IV non-small cell lung cancer patient prior to start immunotherapy treatment Patients with World Health Organization (WHO) performance status 0-3 Patients who were informed and had non opposition form signed by investigator Patients with healthcare insurance system affiliation Exclusion Criteria: Prior malignancy within 5 years of study entry Refusal to participate Patient under legal protection

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Stage IV non-small cell lung cancer<br>Intervention to be done are : - Blood sample collection for CTC and MDSC analysis | Biological: blood sample collection for CTC and MDSC analysis<br>* Isolation of circulating tumor cells from 2 tubes by ISET filtration module. Peripheral blood samples will be collected for CTC analysis within 7 days before commencing treatment (defined as baseline) and following four cycles of immunotherapy, Analysis of PD-L1 and PD-L2 expression by immunocytochemistry on CTC Analysis of the expression of PD-L1, PD-L2 , CTLA4 on the histological specimen by immunohistochemistry<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of analysis of PDL-1 expression on circulating tumor cells as assessed by immunocytochemistry analysis | Prior to immunotherapy, after four cycle of immunotherapy | Through the end of study (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of CTC expressing PD-L1 after four cycle of immunotherapy as assessed by immunocytochemistry analysis | Prior to immunotherapy, after four cycle of immunotherapy | Through the end of study (12 months) | 
| Evolution of MDSCs count in response to treatment as assessed by MDSCs analysis | Prior to immunotherapy, after four cycle of immunotherapy | Through the end of study (12 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, lung cancer, circulating tumor cells, immunocytochemistry, ISET, MDSC, Stage IV non-small cell lung cancer, PD-1/PD-L1, Immune checkpoints