Immune Response Under Immunotherapy in Metastatic NSCLC: Sputum, Blood Samples and Microbioata Study

Completed

• Conditions: Metastatic Lung Cancer; Non-squamous Lung Cancer
• Interventions: Other: Blood; Other: sputum; Other: saliva; Other: stool

• Registration Number: NCT04804137
• Lead Sponsor: University Hospital, Tours

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.

Study Timeline

• Study First Submitted: 2021-03-08
• Study First Submitted QC: 2021-03-16
• Study First Posted: 2021-03-18
• Study Start: 2021-05-03
• Primary Completion: 2022-09-26
• Study Completion: 2023-07-31
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-16
• Last Update Posted: 2024-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group	Blood	adult patients with adenocarcinoma type non-small cell lung cancer
Group	saliva	adult patients with adenocarcinoma type non-small cell lung cancer
Group	stool	adult patients with adenocarcinoma type non-small cell lung cancer
Group	sputum	adult patients with adenocarcinoma type non-small cell lung cancer

Primary Outcome Measures

Name	Time	Method
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)
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)

Secondary Outcome Measures

Name	Time	Method
perform blood pembrolizumab assays.	30 months	antibodies dosage
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 sputum pembrolizumab assays.	30 months	antibodies dosage

Trial Locations

Locations (2)

Ferreira Marion; 🇺🇸 Los Angeles, California, United States

University hospital; 🇫🇷 Tours, France