Non-squamous Lung Cancer, Metastatic Lung Cancer
Conditions
Keywords
Blood sample, sputum, microbiota, Immunotherapy, saliva
Brief summary
Prospective pathophysiological exploratory monocentric study, focusing on adult patients with non-small cell lung cancer (NSCLC) : non-squamous type without oncogenic addiction, metastatic, treated with immune checkpoint inhibitors alone or in combination with chemotherapy in front line at the CHRU de Tours, France.
Detailed description
The percentage of patients benefiting from immunotherapy is quite low and their systemic side effects can sometimes be severe. One of the main difficulties is to identify before treatment patients who will respond to immune checkpoint inhibitors. Currently, the selection is done in a very large majority of cases on the expression of PD-L1 by the tumor. But this biomarker is not sufficient to identify patients responding or not to immune checkpoint inhibitors. In addition, factors extrinsic to the tumor, to its microenvironment and patient immunity may be involved in the response to immunotherapy such as the microbiota. The investigators therefore assume that the immune response in place during immunotherapy treatment differs according to the profile of patient response to immunotherapy. The main objective of this project is to describe local and systemic anti-tumor immune system of patients responders or not to immune checkpoint inhibitors, but also whether the immunological characterization of sputum could be a reflection of the microenvironment tumor. The secondary objective is to study the intestinal microbiota tract of patients receiving immunotherapy, depending on their consumption of antibiotics, and compare it to the pulmonary microbiota.
Interventions
OTHERBlood
Blood samples are taken at each visit to the day hospital for a programmed injection of immunotherapy.
OTHERsputum
induced by saline aerosol sputum during each visit to the day hospital for a programmed injection of immunotherapy.
OTHERsaliva
spontaneous saliva during each visit to the day hospital for a programmed injection of immunotherapy.
OTHERstool
Stool analyses will be carried out on a sample taken by the patient at home and brought back at the time of a day hospital.
Sponsors
Cedars-Sinai Medical Center
University Hospital, Tours
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of 18 years or over * Diagnosis of metastatic NSCLC (Stage IV) adenocarcinoma only * Absence of oncogenic addiction (EGFR, ALK, ROS1, RET, MET, BRAF) * Treatment with ICI anti-PD1 or anti-PDL1 (pembrolizumab or atezolizumab) as 1st line treatment alone or in combination with chemotherapy and/or anti-angiogenic (bevacizumab). * 1st injection of ICI, whether or not combined with chemotherapy
Exclusion criteria
* Patient under judicial protection * Pregnant or breastfeeding women * NSCLC of the epidermal or undifferentiated type * Opposition to data processing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune and inflammatory response in the blood | 30 months | * T cell sub populations assessed by their relative abundance, and will be expressed as a percentage of total T cells * B lymphocytes * Cytokine inflammatory profile: the level of activation/regulation, production of cytokines and cytotoxicity markers will be analysed as a percentage of cells expressing the markers or producing the cytokines in relation to the total cell population (e.g. HLA-DR+, CD38+, Bcl-2lo phenotype of CD8 T lymphocytes) |
| Immune and inflammatory response in the airways | 30 months | * T cell sub populations assessed by their relative abundance, and will be expressed as a percentage of total T cells * B lymphocytes * Cytokine inflammatory profile: the level of activation/regulation, production of cytokines and cytotoxicity markers will be analysed as a percentage of cells expressing the markers or producing the cytokines in relation to the total cell population (e.g. HLA-DR+, CD38+, Bcl-2lo phenotype of CD8 T lymphocytes) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of gut microbiota | 30 months | characterisation of gut microbiota (16S rRNA sequencing) |
| Analysis of lung microbiota | 30 months | characterisation of lung microbiota (16S rRNA sequencing) |
| perform blood pembrolizumab assays. | 30 months | antibodies dosage |
| perform sputum pembrolizumab assays. | 30 months | antibodies dosage |
Countries
France, United States
Outcome results
None listed