Lung Cancer
Conditions
Keywords
PD-1/PD-L1, Immune checkpoints, Immunotherapy, lung cancer, circulating tumor cells, immunocytochemistry, ISET, MDSC, Stage IV non-small cell lung cancer
Brief summary
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
Interventions
BIOLOGICALblood sample collection for CTC and MDSC analysis
* 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
Sponsors
University Hospital, Toulouse
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of analysis of PDL-1 expression on circulating tumor cells as assessed by immunocytochemistry analysis | Through the end of study (12 months) | Prior to immunotherapy, after four cycle of immunotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of CTC expressing PD-L1 after four cycle of immunotherapy as assessed by immunocytochemistry analysis | Through the end of study (12 months) | Prior to immunotherapy, after four cycle of immunotherapy |
| Evolution of MDSCs count in response to treatment as assessed by MDSCs analysis | Through the end of study (12 months) | Prior to immunotherapy, after four cycle of immunotherapy |
Countries
France
Outcome results
None listed