: 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

Sponsors

Lead sponsor: University Hospital, Grenoble

Source University Hospital, Grenoble
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

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.

Overall Status Recruiting
Start Date January 3, 2020
Completion Date November 2021
Primary Completion Date November 2021
Study Type Observational
Primary Outcome
Measure Time Frame
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
Secondary Outcome
Measure Time Frame
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
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
Description of the profile change of Meta-genomic signature 2 months or 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
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)
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)
Description of overall survival under ICI at 6 months or at the tumoral progression 6 months or tumoral progression
Description of the survival without progression under ICI at 6 months or at the tumoral progression 6 months or tumoral progression
Enrollment 60
Condition
Intervention

Intervention type: Other

Intervention name: Immune signature in serum associated to the metabolic signature

Description: Immune signature in serum associated to the metabolic signature

Intervention type: Genetic

Intervention name: Meta-genomic signature of intestinal flora

Description: Meta-genomic signature of intestinal flora

Eligibility

Sampling method: Non-Probability Sample

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

Gender: All

Minimum age: 18 Years

Maximum age: 100 Years

Healthy volunteers: No

Overall Official
Overall Contact

Last name: Anne-Claire TOFFART, Dr

Phone: +33(0)4 76 76 75 75

Email: [email protected]

Location
facility status contact investigator University Hospital, Grenoble Christine Tchikladze +33 (0) 4 76 76 70 32 [email protected] Anne-Claire Toffart, MD, PhD Principal Investigator Denis Moro-Sibilot, MD Sub-Investigator Matteo Giaj Levra, MD Sub-Investigator
Location Countries

France

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Arm group label: First line

Description: 20 patients in first line of treatment

Arm group label: Second or third line

Description: 40 patients in second and third line of treatment

Acronym METABO-ICI
Patient Data No
Study Design Info

Observational model: Cohort

Time perspective: Prospective

Source: ClinicalTrials.gov