Metastatic Lung Cancer
Conditions
Keywords
Lung Cancer NSCLC, metastatic stage, first-line treatment with immunotherapy
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.
Interventions
BIOLOGICALassessment 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).
Sponsors
Institut Curie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Free survival | End of study | Progression-free survival according to immune cell levels in the blood |
| Overall survival | End of study | Overall survival according to immune cell levels in the blood |
| Survival (FS) | End of study | Progression-free survival according to immune cell levels variations in the blood |
| Survival (OS) | End of study | Overall survival according to immune cell levels variations 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. |
| 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. |
| Adverse events of special interest | End of study | Adverse events of special interest of grade 3 or more (CTCAE v5.0). |
| Progression-free | End of study | Progression-free survival according to ctDNA level variations. |
Countries
France
Contacts
Primary ContactMarie-Emmanuelle Legrier
Outcome results
None listed