Trial to Evaluate Safety and Efficacy of Vinorelbine With Metronomic Administration in Combination With Atezolizumab as Second-line Treatment for Patients With Stage IV Non-small Cell Lung Cancer

Inclusion Criteria:

* Histologically confirmed NSCLC;
* Locally advanced and/or metastatic stage IV NSCLC (according to American Joint Committee on Cancers) or recurrent NSCLC);
* Patients without activating EGFR mutation or ALK rearrangement and ROS1 fusions.
* Subject has provided a formalin-fixed tumor-tissue sample of a tumor-lesion biopsy, either at the time of or after metastatic disease was diagnosed AND from a site not previously irradiated to assess for PDL1 status. Archived tissue may be acceptable or PDL1 status known;
* Progressive disease after first-line platinum-doublet-based chemotherapy according to RECIST V.1.1 with measurable lesion (RECIST V1.1);
* Age ≥18 years, either sex;
* Eastern Collaborative Oncology Group Performance status (ECOG PS) 0, 1 or 2;
* Life expectancy exceeds 12 weeks;
* No history of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin;
* Adequate organ function, demonstrated by the following laboratory results within 3 weeks prior to teatment: Normal hepatic function: bilirubin \<1.5 × normal (N), Alanine aminotransferase and Aspartate aminotransferase \<2.5 × N or \<5 × N if liver metastasis is present;
* Normal renal function (calculated creatinine clearance ≥45 mL/min);
* Normal calcemia;
* Normal hematological function (polynuclear neutrophils \>1.5 G/L, platelets \>100 G/L and hemoglobin\>8g/dl);
* Women of child-bearing potential must use effective contraception;
* Men might be surgically sterile or accept to use an effective contraceptive procedure during and until 6 months after the treatment;
* Written informed consent to participate in the study
* Patient with social insurance

Exclusion Criteria:

* ECOG PS \>2;
* Known hypersensitivity to immunotherapy;
* Small-cell lung cancer, bronchioloalveolar cancer, neuroendocrine cancer;
* Tumor harbors EGFR-sensitizing (activating) mutations or ALK translocations or ROS1 fusions and that justify treatment with targeted therapy ;
* Chemotherapy, hormonotherapy, immunotherapy or tyrosine-kinase inhibitors within the past 4 weeks prior to treatment with the trial drug;
* Radiotherapy (except bone or brain) within the past 3 months prior to baseline imaging;
* Medical contraindication to oral vinorelbine;
* Persistence of clinical adverse events with a grade \> 2 related to prior treatment;
* Active brain metastases (e.g. stable for \<4 weeks, no adequate previous radiotherapy, symptomatic, requiring anticonvulsants or corticosteroids)
* Concurrent radiotherapy, except for palliative bone irradiation.
* Other concurrent severe illnesses (congestive heart failure, unstable angina, significant arrhythmia or myocardial infarction \<12 months before study entry);
* Active or prior documented autoimmune or inflammatory disorders;
* Active B hepatitis, HIV infection …;
* Psychiatric or neurological disorders preventing the patient from understanding the nature of the trial;
* Grade-3 peripheral neuropathy;
* Uncontrolled infection;
* Interstitial lung disease or pneumonitis requiring steroid management;
* Corticosteroid therapy exceeding 10 mg/day;
* Other severe organic disorders not allowing inclusion in the trial;
* Malabsorption syndrome;
* Pregnancy or breast-feeding;
* Follow-up not possible; and incarcerated or institutionalized patients.