Radar des Essais Cliniques

• Informed, written and signed consent: Patients must have signed and dated the written informed consent form approved by the ethics committee in accordance with the legal and institutional framework. It must have been signed before protocol-related procedures that are not part of normal patient management are performed. Patients should be willing and able to adhere to the schedule of visits, treatment and laboratory tests.
• Patients with radiological ILDs. All cases should be presented in a multidisciplinary board dedicated to ILD to confirm eligibility. In centres without a local multidisciplinary board dedicated to ILD, the national multidisciplinary board CAPID can be used.
• NSCLC proven histologically. Cytological evidence is allowed if a cytoblock has been prepared.
• Age ≥ 18 years old.
• Performance status ≤ 2.
• Stage IIIB or IIIC non-eligible to radiation therapy or IV (8th TNM classification, UICC 2015). For other less advanced stages but rejected for any local treatment, possible inclusion discussion with the sponsor.
• Disease measurable according to RECIST criteria 1.1 per investigator assessment.
• Adequate biological function: Creatinine clearance ≥ 45 mL/min (Cockroft or MDRD or CKD-epi); neutrophils ≥ 1500/mm3; platelets ≥ 100,000/mm3; Haemoglobin ≥ 9 g/dL; liver enzymes< 3x ULN except for patients with liver metastases (< 5x ULN); total bilirubin ≤ 1.5x ULN except for patients with proven Gilbert's syndrome (≤ 5x ULN) or patients with liver metastases (≤ 3.0 mg/dL).
• Life expectancy of at least 12 weeks.
• For female patients of childbearing potential and patients with a partner of childbearing potential, agreement (by the patient and/or partner) to use one or more highly effective contraceptives (failure rate < 1% per year when used correctly and regularly) and to continue using it for 7 months after the last dose of treatment. Men should not donate their sperm for the duration of the study and for at least 7 months after the last dose of treatment. Oral contraception should always be combined with another method of contraception because of potential interactions with treatment. Patients should always use a condom.
• Patient covered by national health insurance.
• Protected adults may participate in the study if they can make decisions regarding their medical treatment in accordance with the guardianship judgment.

Inclusion Criteria for first-line part:

• Patient must be treatment naive for advanced or metastatic disease. Treatment for non-metastatic stage is not considered as a line if there is a time interval of at least 6 months between the last dose of treatment for non-metastatic stage and recurrent disease.
• ILD criteria: any type of ILD and any level of severity are allowed Inclusion criteria specific to second-line part
• Patients must have received one but no more than one platinum-based therapy for advanced or metastatic disease. Treatment for non-metastatic stage is not considered as a line if there is a time interval of at least 6 months between the last dose of treatment for non-metastatic stage and recurrent disease.
• ILD severity criteria: Patients with ILDs with mild to moderate alteration of pulmonary function, defined by Forced Vital Capacity (FVC) ≥ 50% of the predicted value AND DLCO≥ 35% of the of the predicted value. All cases should be presented in a multidisciplinary board dedicated to ILD to confirm eligibility. In centers without a local multidisciplinary board dedicated to ILD, the national multidisciplinary board CAPID can be used.
• ILD type criteria: Patient with idiopathic interstitial pneumonia (including IPF and NSIP) or secondary ILDs (including hypersensitivity pneumonia, pneumoconiosis, radiation pneumonitis) could be included. Will be excluded patients with ILDs secondary to connective tissue disease, vasculitis or granulomatosis (including but not limited to granulomatosis with polyangiitis, rheumatoid arthritis, Sjogren's syndrome, scleroderma, myositis/dermatomyositis, anti-synthetase syndrome). For sarcoidosis and for Interstitial pneumonia with autoimmune features (IPAF) inclusion could be confirmed based on a case-by-case discussion with the sponsor.
• Available results for Immunoassay including antinuclear antibodies tested by immunofluorescence, rheumatoid factor, anti-CCP, Anti-dsDNA, Anti-Ro (SS-A), Anti-La (SS-B), Anti-ribonucleoprotein, Anti-Smith, Anti-topoisomerase (Scl-70), Anti-tRNA synthetase (Jo-1, PL-7, PL-12, Anti-PM-Scl, Anti-MDA-5), ANCA.