Stage IV or non-treatable by radiotherapy or surgery stage III (7th classification)
No previous systemic chemotherapy for lung cancer, except in case of relapse after adjuvant treatment for localized disease with 6 months or more between end of previous chemotherapy and relapse
Patients less than 70 years old and PS 2 or 70 years older PS 0 to 2
Judged fit enough to receive a carboplatin based doublet according to ESMO guidelines
Presence of at least one measurable target lesion (RECIST 1.1 rules) in a non-irradiated region and analysable by CT
Life expectancy superior at 12 weeks
Prior radiation therapy is authorized if it involved less than 25% of the total bone marrow volume and finished 14 days before D1 of planned treatment
Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization/registration WBC superior or equal at at 2000/μL Neutrophils superior or equal at at 1500/μL Platelets superior or equal at at 100 x103/μL Hemoglobin superior at 10.0 g/dL Serum creatinine inferior or equal at 1.5 x ULN or creatinine clearance (CrCl) superior or equal at at 45 mL/min (if using the Cockcroft-Gault formula ) AST/ALT inferior or equal at 3 x ULN Total Bilirubin inferior or equal at 1.5 x ULN (except Patients with Gilbert Syndrome, who can have total bilirubin inferior at 3.0 mg/dL)
Availability of adequate FFPE tumor-derived material (tumor blocks or slides) from a biopsy, surgery or fine needle aspirate for analysis of PD-L1 testing by IHC
Age and Reproductive Status
Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during treatment.
WOCBP should use an adequate method to avoid pregnancy :
For 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of nivolumab + ipilimumab,
For 4 weeks after the last dose of carboplatine + pemetrexed,
For 5 weeks after the last dose of carboplatine + paclitaxel.
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of treatment
* Women must not be breastfeeding
* Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during treatment Men will be instructed to adhere to contraception for a period of 31 weeks after the last dose of nivolumab + ipilimumab and with carboplatine +pemetrexed or carboplatine + paclitaxel up to 6 months thereafter.
Patients should be excluded if they have an active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (superior at 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses superior at 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Patients should be excluded if they have a lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
Allergies and Adverse Drug Reaction
History of allergy to study drug components
Severe spinal hypoplasia and / or hemorrhagic tumors
You may not be if
Serious or uncontrolled systemic disease judged as incompatible with the protocol by the investigator
Another previous or concomitant cancer, except for basocellular cancer of the skin or treated cervical cancer in situ, or appropriately treated localized low-grade prostate cancer (Gleason score inferior at 6), unless the initial tumor was diagnosed and definitively treated more than 5 years previously, with no evidence of relapse.
Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation
Superior at caval syndrome
Uncontrolled infectious status
All concurrent radiotherapy
Concurrent administration of one or several other anti-tumor therapies.
Psychological, familial, social or geographic difficulties preventing follow-up as defined by the protocol.
Protected person (adults legally protected (under judicial protection, guardianship or supervision), person deprived of their liberty, pregnant woman, lactating woman and minor),
Concurrent participation in another clinical trial
Clareo Health | Nivolumab and Ipilimumab Versus Chimiotherapy in First Line Treatment in PS 2 or Elderly in Advanced NSCLC Patients
