LIquid Biopsy to prEdict Responses To First-line immunotherapY in Metastatic Non-small Cell LUNG Cancer. LIBERTY LUNG

Study Overview
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Brief Summary
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Patient with histologically proven NSCLC in a metastatic stage, treatment naïve and eligible for first-line treatment with immune checkpoint inhibitor. Combination with chemotherapy is possible. Presence of a mutation after NGS analysis is required for ctDNA follow-up.

Detailed Description
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A pre-screening consent will be obtained for NGS analysis on tumor tissue. Only patients with at least 1 mutation at NGS on the tumor tissue will ultimately be enrolled in the study, to have the possibility to follow the mutation using ctDNA. Main consent will be obtained after results of the NGS and before initiation of pembrolizumab. Computed Tomography (CT)-scan imaging will be done every 9 weeks as part of routine care practice. Blood specimens will be taken with EDTA tubes or streck tubes at the time of puncture for pembrolizumab infusion at baseline before starting treatment, at 3 weeks, 6 weeks and then every 6 weeks. Blood immunomonitoring will be done before starting the treatment, at 6 weeks and at 18 week. An additional measurement will be performed if treatment is stopped before the end of the study. - Optional blood samples will be realized to analyse the degree of activity of the plasmatic lymphocytes.

Official Title
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LIquid Biopsy to prEdict Responses To First-line immunotherapY in Metastatic Non-small Cell LUNG Cancer

Conditions
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NSCLC Patient in a Metastatic Stage Eligible for First-line Treatment With Immune Checkpoint Inhibitor

Intervention / Treatment
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* Biological: assessment of the predictive value of ctDNA level of the prominent mutant allele variation between baseline and week 6, on response to treatment according to RECIST 1.1 criteria.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven NSCLC. Age ≥ 18 years. Advanced or metastatic stage IV. Treatment-naïve patient. Eligibility to first-line treatment with immune checkpoint inhibitor. Measurable disease according to RECIST 1.1 criteria on CT-Scan. Availability of expression of PD-L1 at immunohistochemistry analysis of the tumor biopsy. No ALK or EGFR gene alteration. Availability of tumor tissue for NGS analysis (7 slides). PS 0 or 1. Signed informed consent of the patient. Exclusion Criteria: No social security affiliation. Person under legal protection. Pregnant and breastfeeding women. Patients can participate to another clinical trial that is not modifying immunotherapy or immunotherapy/chemotherapy treatment nor study follow-up ; after investigator's information

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NSCLC patient in a metastatic stage eligible for 1st-line TT with immune checkpoint inhibitor.<br> | Biological: assessment of the predictive value of ctDNA level of the prominent mutant allele variation between baseline and week 6, on response to treatment according to RECIST 1.1 criteria.<br>* At pre-screening NGS analysis on tumor tissue (slides). Only patients with at least 1 mutation at NGS on the tumor tissue will ultimately be enrolled in the main study, to have the possibility to follow the mutation using ctDNA. Main study will be initiated after results of the NGS and before initiation of pembrolizumab. Blood specimens will be taken with EDTA tubes or streck tubes at the time of puncture for pembrolizumab infusion at baseline before starting treatment, at 3 weeks, 6 weeks and then every 6 weeks (30 ml at Baseline then 20 ml of blood). Blood immunomonitoring will be done before starting the treatment, at 6 weeks and at 18 Week. An additional measurement will be performed if treatment is stopped before the end of the study (18 ml of blood). Optional blood samples will be realized to analyse the degree of activity of the plasmatic lymphocytes before starting the treatment and at 6 weeks and (18 ml of blood).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ctDNA variation of the prominent mutant allele variation | ctDNA variation of the prominent mutant allele variation between baseline and week 6, on response to treatment defined as the proportion of patients who will achieve a complete or partial response at CT-scan based on RECIST 1.1 criteria. | 6 weeks on response to treatment defined as the proportion of patients who will achieve a complete or partial response at CT-scan based on RECIST 1.1 criteria | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ctDNA variation of the prominent mutant allele variation | ctDNA variation of the prominent mutant allele variation between baseline and week 6, on response to treatment defined as the proportion of patients who will achieve a complete or partial response at CT-scan based on iRECIST criteria. | 6 weeks on response to treatment defined as the proportion of patients who will achieve a complete or partial response at CT-scan based on iRECIST criteria. | 
| Progression-free survival | Progression-free survival according to immune cell levels in the blood | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Overall survival | Overall survival according to immune cell levels in the blood | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Progression-free survival | Progression-free survival according to immune cell levels variations in the blood | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Overall survival | Overall survival according to immune cell levels variations in the blood | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Progression-free | Progression-free survival according to ctDNA level variations. | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Overall survival | Overall survival according to ctDNA level variations. | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Response rate to the second line of treatment | Response rate to the second line of treatment based on RECIST 1.1 and iRECIST criteria according to ctDNA level at week 6 of the second line of treatment. | 6 weeks after progression after first-line treatment or a maximum of 21 months | 
| Adverse events of special interest | Adverse events of special interest of grade 3 or more (CTCAE v5.0). | 6 weeks after progression after first-line treatment or a maximum of 21 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer NSCLC, metastatic stage, first-line treatment with immune checkpoint inhibitor