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

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

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Patient in a Metastatic Stage Eligible for First-line Treatment With Immune Checkpoint Inhibitor
• Intervention / Treatment: 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.

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 Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cyrine EZZILI; Phone Number: 01 47 11 16 57; Email: cyrine.ezzili@curie.fr

Study Locations

• France
  • Boulogne Billancourt, France, 92100
    • Not yet recruiting
    • Hôpital Ambroise Paré
    • Contact: Etienne GIROUX LE PRIEUR, PR
    • Principal Investigator: Etienne GIROUX LE PRIEUR, PR
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
    • Contact: Nicolas GIRARD, PR
    • Sub-Investigator: Nicolas GIRARD, PR
  • Saint-cloud, France, 92210
    • Recruiting
    • Institut Curie
    • Contact: Marie-Ange MASSIANI, DR
    • Principal Investigator: Marie-Ange MASSIANI, DR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NSCLC patient in a metastatic stage eligible for 1st-line TT with immune checkpoint inhibitor.

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.; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Study Director: Nicolas GIRARD, PR, INSTITUT CURIE - Medical Oncology; Study Chair: Pierre FUMOLEAU, INSTITUT CURIE - Medical Oncology

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2021
• Primary Completion (Estimated): October 9, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer NSCLC; metastatic stage; first-line treatment with immune checkpoint inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: IC 2020-02 Liberty Lung

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• IPD Sharing Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No