Non Small Cell lung cancer (NSCLC) remains the first cause of death by cancer in the World. For the patients presenting a NSCLC stage IV, the median of survival is about 15 months today. The chemotherapy with platinum is the standard treatment for these patients but immunotherapy showed these efficacy in 1st line for patients PD-L1 positive. On the other hand, the duration of treatment by immunotherapy is not clear. Indeed, prolonged responses and long survivals have been described in patients having interrupted the treatment. In the melanoma, a treatment of 6 months of ipilimumab demonstrated its efficacy. The objective of the study is to demonstrate that a treatment of 6 months followed by an observation (stop and go) is not less effective than a treatment given until progression or toxicity. This strategy would allow to decrease the accumulated toxicities, to improve the quality of life of the patients and to decrease the costs.
Name: Ipilimumab
Name: Nivolumab
Description: Time between the date of randomization and the first date of documented progression, as determined by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first.
Measure: Progression Free Survival (PFS1) Time: 24 months after randomization of the last subjectDescription: Time between the start date of the second line and the second date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first.
Measure: Progression Free Survival (PFS2) Time: 24 months after randomization of the last subjectDescription: Time until definitive deterioration (TUDD) from the randomization time in the experimental arm B.
Measure: Quality of life (QoL) Time: 24 months after randomization of the last subjectDescription: PD-L1-stained % of tumor cells will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (PD-L1) Time: 6 monthsDescription: PD-L1 H-score will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (PD-L1 H score) Time: 6 monthsDescription: CD3/CD8 tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (CD3/CD8) Time: 6 monthsDescription: neutrophil tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (neutrophil) Time: 6 monthsDescription: plasma concentration of different cytokines at baseline or at the randomization point, will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (cytokines) Time: 6 monthsDescription: plasma concentration of different chemokines at baseline or at the randomization point, will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS
Measure: Biological correlative exploratory studies (chemokines) Time: 6 monthsAllocation: Randomized
Parallel Assignment
There are 2 SNPs
Exclusion Criteria: 1. Small cell lung cancer or tumors with mixt histology including a SCLC component 2. Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER exon 20 insertion (either tissue or plasma cfDNA mutation). --- L858R --- --- G719A ---
Exclusion Criteria: 1. Small cell lung cancer or tumors with mixt histology including a SCLC component 2. Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER exon 20 insertion (either tissue or plasma cfDNA mutation). --- L858R ---