1st Line Durvalumab in PS 2 NSCLC Patients

Inclusion Criteria: * Written informed consent according to Swiss law and ICH/GCP regulations before registration and prior to any trial specific procedures * Histologically confirmed NSCLC, advanced or recurrent disease (stage IIIB to IV). Cytology could be accepted if histology is not possible * PD-L1 expression of ≥ 25% of the tumor cells by local testing (Ventana SP142 excluded) * No sensitizing EGFR mutation (L858R or exon 19 deletions), ALK fusion oncogene or rearrangements of the ROS1 gene detected in patients with a non-squamous cell NSCLC * Patient unsuitable for platinum-containing combination chemotherapy according to investigator or due to patient preference * WHO PS of 2. Confirmation of PS2 by a second medical doctor is mandatory. * Age ≥ 18 years * Baseline QoL forms and GA questionnaires have been completed * Bone marrow function: hemoglobin ≥ 90 g/L, neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L * Hepatic function: bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN); patients without liver metastases: AST and ALT ≤ 2.5 x ULN, patients with documented liver metastases: AST and ALT ≤ 5 x ULN * Renal function: estimated glomerular filtration rate (eGFR)\> 30 mL/min/1.73m² (according to CKD-EPI formula) * Measurable or evaluable disease (by RECIST v1.1) * Patients with asymptomatic untreated CNS metastases are eligible, provided they meet the following: * ≤ 5 CNS lesions with a maximum diameter of one lesion of 10 mm * Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, cerebellum, medulla, or spinal cord) * No evidence of progression at registration compared to the latest brain imaging * No ongoing requirement for corticosteroids as therapy for CNS disease * Patients with symptomatic treated CNS metastases are eligible, provided they meet the following: * No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed * No stereotactic radiation or whole-brain radiation within 7 days prior to registration * No evidence of progression at registration, after completion of CNS-directed therapy * Tumor tissue available for central PD-L1 assessment and translational research (preferably histology but cytology could be allowed if histology is not possible). In case of scarce tumor material, a rebiopsy, if clinically possible, is encouraged * Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and during the 3 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential * Men agree not to father a child during trial treatment and during 3 months thereafter * Body weight \> 30kg. * Life expectancy \> 3 months. Exclusion criteria: Any potential patient who meets any of the following criteria has to be excluded from entering the trial. * History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years before registration with the exception of pT1-2 prostate cancer Gleason score \<6, adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer * Prior adjuvant systemic anti-cancer treatment within 6 months before registration * Prior systemic treatment for metastatic NSCLC * Prior treatment with a PD-1 or PD-L1 inhibitor * Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (i.e. which must not exceed 10 mg/day of prednisone or an equivalent corticosteroid) * Concomitant drugs contraindicated for use with durvalumab such as corticosteroids, methotrexate, azathioprine and tumor necrosis factor (TNF)-α blockers * Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 28 days prior to registration * Major surgical procedure within 14 days prior to registration * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], 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 the coordinating investigator * Patients with celiac disease controlled by diet alone * Uncontrolled diabetes mellitus * Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment * Known history of tuberculosis * Known history of primary immunodeficiency * Known history of allogeneic organ transplant * Receipt of live attenuated vaccine within 28 days prior to registration * Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV; unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled hypertension * Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications. * Patients with dyspnea grade ≥ 3 according to the modified Medical Research Council (mMRC) dyspnea scale. * Patients with symptomatic pneumonitis (grade ≥ 2) or active lung infection. Patients having fully recovered from active lung infection can be included assumed they have completed antibiotics and/or corticosteroids * Patients with disseminated intravascular coagulopathy * Patient with a baseline CT scan older than 21 days prior to registration.