Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma

: Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma

Immune checkpoints inhibitors (ICI) are becoming new standards of care for Non-Small Cell Lung Carcinoma (NSCLC) treatment. To date, no powerful predictive biomarker of response has been found.

The investigators hypothesize that metabolomics profile could represent a potent biomarker of response to ICI

Immune checkpoints inhibitors (ICI) are becoming new standards of care for Non-Small Cell Lung Carcinoma (NSCLC) treatment, both as first and second line of treatment. To date, no powerful predictive biomarker of response has been found. It has been recently shown that microbiota composition could dictate the ability of patients to respond to ICI. Since, the microbiota produces circulating metabolites that will subsequently act on immune system, the investigators hypothesized that metabolic signature, reflecting microbiota function, could represent a predictive biomarker of response to ICI.

Primary objective is to identify baseline metabolic signature (metabolomics analysis by Mass spectrometry) associated to ICI response. Secondary objectives are to link metabolic signature with microbiota composition (metagenomics analysis RNA 16S) and immune profile, and altogether with clinic response to ICI. Profile evolution (metabolic, metagenomics and immune) will be also analyzed at 2-month post ICI initiation and at tumor progression, if any.

In order to do so, the investigators thus plan to enroll 60 NSCLC patients treated by ICI as 1st, 2nd or 3rd line of treatment in CHUGA in 18 months. Blood as well feces will be collected prior to, and at 2 month following ICI treatment initiation as well as at progression. Will be excluded from this study, patients that have received antibiotic or corticotherapy 2 or 4 weeks before ICI initiation, respectively.

Inclusion Criteria:

• NSCLC diagnosis
• Patient treated by a ICI in first, second or third line of treatment, or by the combination of chemotherapy and IPCI in first line of treatment
• Patient with at least one measurable lesion as defined by RECIST

Exclusion Criteria:

• Patient treated with antibiotic treatment within 2 weeks before the start of ICI or corticosteroids (>20 mg per day) within 4 weeks before the start of ICI