Immunotherapy in Patient With Poor General Condition

Inclusion Criteria: 1. Subjects must have signed and dated an IEC (Independent Ethic Committee) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing. 2. Histologically or cytologically-proven NSCLC (squamous or non-squamous). If the diagnosis is cytologically-proven, sufficient material is necessary with at least 100 tumor cells evaluated for PD-L1 IHC (Immunohistochemistry). 3. PD-L1 expression ≥25% of tumor cells as assessed by the local pathology laboratory using protocols validated. 4. Available tumor samples for centralized PD-L1 immunohistochemistry analysis. 5. No EGFR (Epidermal Growth Factor Receptor) mutation and no ALK(Anaplasic Lymphoma Kinase) gene rearrangement. 6. Stage IV (8th classification TNM) M1a or M1b or M1c. 7. ECOG (Eastern Cooperative Oncology Group) PS = 2 or 3 despite optimal symptomatic treatment. 8. Body weight \>30kg 9. No prior systemic anticancer therapy (chemotherapy, immunotherapy including durvalumab, or EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease. Neoadjuvant or adjuvant chemotherapy is not considered as chemotherapy for advanced or metastatic disease. 10. Limited field of radiation for palliation within 2 weeks of the first dose of durvalumab is allowed, provided the lung is not in the radiation field and irradiated lesion(s) cannot be used as target lesions. 11. Age 18-75 years. 12. Measurable tumor disease by CT per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 13. Life expectancy \> 8 weeks according to the investigator opinion. 14. Adequate biological functions: neutrophils ≥ 1500/mm3 ; platelets ≥ 75 000/mm3 ; Hemoglobin ≥ 9 g/dL ; Creatinine Clearance \> 40 mL/min , AST and ALT ≤ 2,5 ULN unless liver metastases are present, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 5 x ULN, serum bilirubin ≤ 1.5 x ULN except for patients with proved, Gilbert syndrome (≤ 5 x ULN) or patients with hepatic metastases (≤ 3 x ULN). 15. Other investigations detailed in Section 5 must have been performed within the timelines indicated. 16. Protocol treatment is to begin within 7 days of patient inclusion. 17. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 18. Females of childbearing potential who are sexually active with a nonsterilized male partner or men who are sexually active with women of childbearing potential must use a highly effective method of contraception prior the first dose of investigational product, and must agree to continue using such precautions for 90 days after the final dose of investigational product. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Exclusion Criteria: 1. Pure or combined SCLC. 2. Known HER2 (Human Epidermal Growth Factor Receptor), B-Raf, activating tumor mutations, or exon 14 c-MET splice mutations (mesenchymal-epithelial transition), or known ROS1 gene rearrangement. 3. Asymptomatic or symptomatic brain metastasis. 4. Carcinomatous meningitis. 5. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with IFCT * Patients with celiac disease controlled by diet alone 6. Immunosuppressive treatment including systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 15 days before enrollment. Inhaled, nasal or topic corticosteroids are allowed. 7. History of allogenic organ transplantation. 8. Stage 4 (very severe, FEV1 (forced expiratory volume at one second) \<30% predicted) chronic obstructive pulmonary disease (COPD) according to GOLD classification. 9. NYHA (New York Heart Association) class 4 chronic heart failure 10. Pre-existing interstitial lung. 11. History of another primary malignancy except for : * Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of IP (Investigational Product) and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of residual disease Patients with a prostate adenocarcinoma history within the previous 5 years could be included in case of localized prostate cancer. 12. Living attenuated vaccine received within the 30 previous days. 13. Received any other experimental treatment or participation to any other therapeutic clinical trial. 14. Known allergy or hypersensitivity to any of the study drug or any of the study drug excipients. 15. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 16. Major surgical procedure within 28 days prior to the first dose of IP or planned surgical procedure during treatment. 17. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs (Adverse Events) or compromise the ability of the patient to give written informed consent. 18. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result) and hepatitis C,. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. History of active tuberculosis or evident primo-infection for which there is no record or evidence of an active anti-tuberculous treatment (please consult IFCT in case of doubt). 19. Patient with human immunodeficiency virus (positive HIV ½ antibodies) 20. Any condition that, in the opinion of investigator, could compromise the adherence to treatment and follow-up. 21. Mental illness or psychological condition, which in the opinion of investigator could compromise the expression of the informed consent. 22. No public health insurance.