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

Not Applicable

Recruiting

• Conditions: Metastatic Lung Cancer
• Interventions: 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.

• Registration Number: NCT04790682
• Lead Sponsor: Institut Curie

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-03-05
• Study First Submitted QC: 2021-03-05
• Study First Posted: 2021-03-10
• Study Start: 2021-05-27
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-26
• Last Update Posted: 2024-07-29
• Primary Completion: 2027-06-02
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Histologically-proven NSCLC.
2. Age ≥ 18 years.
3. Advanced or metastatic stage IV.
4. Treatment-naïve patient.
5. Eligibility to first-line treatment with immune checkpoint inhibitor.
6. Measurable disease according to RECIST 1.1 criteria on CT-Scan.
7. Availability of expression of PD-L1 at immunohistochemistry analysis of the tumor biopsy.
8. No ALK or EGFR gene alteration.
9. Availability of tumor tissue for NGS analysis (7 slides).
10. PS 0 or 1.
11. Signed informed consent of the patient.

Exclusion Criteria

1. No social security affiliation.
2. Person under legal protection.
3. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NSCLC patient in a metastatic stage eligible for 1st-line TT with immune checkpoint inhibitor.	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.	Patient with histologically proven Non Small Cell Lung Cancer 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.

Primary Outcome Measures

Name	Time	Method
ctDNA variation of the prominent mutant allele variation	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	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.

Secondary Outcome Measures

Name	Time	Method
Progression-free	End of study	Progression-free survival according to ctDNA level variations.
Survival (FS)	End of study	Progression-free survival according to immune cell levels variations in the blood
Survival	End of study	Overall survival according to ctDNA level variations.
Response rate to the second line of treatment	End of study	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.
Overall survival	End of study	Overall survival according to immune cell levels in the blood
ctDNA variation of the prominent mutant allele variation	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.	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.
Free survival	End of study	Progression-free survival according to immune cell levels in the blood
Survival (OS)	End of study	Overall survival according to immune cell levels variations in the blood
Adverse events of special interest	End of study	Adverse events of special interest of grade 3 or more (CTCAE v5.0).

Trial Locations

Locations (2)

Hopital Ambroise Pare; 🇫🇷 Boulogne Billancourt, France

Institut Curie; 🇫🇷 Saint-cloud, France