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

Immune Response Under Immunotherapy in Metastatic Non-Small Cell Lung Cancer: Sputum, Blood Samples and Microbiota Study

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Lung Cancer; Non-squamous Lung Cancer
• Intervention / Treatment: Other: Blood; Other: sputum; Other: saliva; Other: stool

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 Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• France
  • Tours, France, 37000
    • University Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Ferreira Marion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

adult patients suffering from adenocarcinoma type non-small cell lung cancer (NSCLC) without oncogenic addiction, metastatic, treated by ICI alone or in combination with 1st line chemotherapy at the Tours CHRU.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Group; adult patients with adenocarcinoma type non-small cell lung cancer

Other: Blood; Blood samples are taken at each visit to the day hospital for a programmed injection of immunotherapy.; Other: sputum; induced by saline aerosol sputum during each visit to the day hospital for a programmed injection of immunotherapy.; Other: saliva; spontaneous saliva during each visit to the day hospital for a programmed injection of immunotherapy.; Other: stool; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune and inflammatory response in the blood	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)	30 months
Immune and inflammatory response in the airways	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)	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of gut microbiota	characterisation of gut microbiota (16S rRNA sequencing)	30 months
Analysis of lung microbiota	characterisation of lung microbiota (16S rRNA sequencing)	30 months
perform blood pembrolizumab assays.	antibodies dosage	30 months
perform sputum pembrolizumab assays.	antibodies dosage	30 months

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Collaborators: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Marion FERREIRA, University Hospital, Tours

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): September 26, 2022
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; sputum; microbiota; saliva; Blood sample
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: RIPH3-RNI20-RICEPS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No