METABO-ICI: Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| First line 20 patients in first line of treatment |
Other: Immune signature in serum associated to the metabolic signature
Immune signature in serum associated to the metabolic signature
Genetic: Meta-genomic signature of intestinal flora
Meta-genomic signature of intestinal flora
|
| Second or third line 40 patients in second and third line of treatment |
Other: Immune signature in serum associated to the metabolic signature
Immune signature in serum associated to the metabolic signature
Genetic: Meta-genomic signature of intestinal flora
Meta-genomic signature of intestinal flora
|
Outcome Measures
Primary Outcome Measures
- Identification of the change from baseline Metabolic signature as predictive factor of the ICI response at 6 months or at the tumoral progression [baseline, 6 months or tumoral progression]
To identify the link of the change from baseline of Metabolic signature in serum (metabolomics analysis performed using a Mass spectrometry) and the ICI response at 6 months or at the tumoral progression
Secondary Outcome Measures
- Identification of the link between the Meta-genomic and immune signatures and the metabolic signature at 6 months or at the tumoral progression [6 months or tumoral progression]
To identify the link between the Meta-genomic signature of intestinal flora (microbiota composition analysed by RNA 16 S) with the Immune signature in serum and the metabolic signature at 6 months or at the tumoral progression
- Identification of the link between the Meta-genomic and immune signatures and ICI response at 6 months or at the tumoral progression [6 months or tumoral progression]
To identify the link between the Meta-genomic signature of intestinal flora with the Immune signature in serum and the ICI response at 6 months or at the tumoral progression
- Description of the profile change of Meta-genomic signature [2 months or tumoral progression]
To describe the change from baseline of the Meta-genomic signature at 2 months or at the tumoral progression
- Description of the profile change of Immune signature at 2 months or at the tumoral progression [Baseline and 2 months or tumoral progression]
To describe the change from baseline of the Immune signature at 2 months or at the tumoral progression
- Identification of the link between the profile change of meta-genomic signature and the ICI response at 2 months or at the tumoral progression [Baseline and (2 months or tumoral progression)]
To identify the link between the profile change from baseline of meta-genomic signature and the ICI response at 2 months or at the tumoral progression
- Identification of change of immune signature and the ICI response at 2 months or at the tumoral progression [Baseline and (2 months or tumoral progression)]
To identify the link between the profile change from baseline of immune signature and the ICI response at 2 months or at the tumoral progression
- Description of overall survival under ICI at 6 months or at the tumoral progression [6 months or tumoral progression]
To describe of the overall survival under ICI at 6 months or at the tumoral progression
- Description of the survival without progression under ICI at 6 months or at the tumoral progression [6 months or tumoral progression]
To describe the survival without progression under ICI at 6 months or at the tumoral progression
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital, Grenoble | La Tronche | Isère | France | 38700 |
Sponsors and Collaborators
- University Hospital, Grenoble
Investigators
- Principal Investigator: Anne-Claire Toffart, Dr, University Hospital, Grenoble
- Study Director: Dalil Hannani, PhD, Medicine University, Grenoble
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 38RC19.133
- 2019-A01255-52