• Age ≥ 18 years at the time of study entry;

• Locally documented histological diagnosis of Large-Cell NeuroEndocrine Carcinoma of the lung (2021 WHO classification of Lung Tumors );

• Patient must have sufficient material to achieve central histological confirmation and exploratory analyses (1 representative FFPE block or at least 10 unstained slides);

• Setting of the disease: locally advanced (Stage III) not eligible for loco-regional therapy or metastatic (Stage IV) in first line treatment (8th TNM classification).

• Nota Bene: patients with recurrence of local or locally advanced LCNEC are eligible to the trial provided that recurrence occurs beyond 3 months after the last chemotherapy administration.

• For relapsing patients, tumor material collected at diagnosis can be used for the FIRST-NEC trial if relapse occurs within two years of initial management and if initial histologic tumor material is available.

• Measurable disease as per the RECIST 1.1;

• Performance Status (PS) of the Eastern Cooperative Oncology Group (ECOG): 0 or 1 ;

• Body weight \> 30Kg;

• Must have a life expectancy of at least 12 weeks;

• Adequate normal organ and marrow function as defined below:

‣ Haemoglobin ≥8.0 g/dL (with or without transfusion)

⁃ Absolute neutrophil count (ANC) ≥1.5 × 109 /L

⁃ Platelet count ≥100 × 109/L

⁃ Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)), or ≤3.0xULN in case of liver metastases.

• Note: this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.

⁃ AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN

⁃ For patients undergoing a treatment by cisplatin: measured creatinine clearance (CrCl) ≥60 mL/min or Calculated creatinine CrCl ≥60 mL/min by the CKD-EPI equation or by 24-hour urine collection for determination of creatinine clearance (CrCl).

• Nota Bene: if creatinine clearance is \<60 ml/min, patients must be treated with carboplatin rather than cisplatin.

⁃ 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).

⁃ Patient (male or female) using a highly effective contraception as defined in during the treatment period and at least up to 6 months after the last administration of chemotherapy or 90 days after the last administration of durvalumab, whichever is longer. Prior to dispensing study drugs, the investigator must confirm and document the patient's (and his/her partner) use of highly effective contraceptive methods, dates of negative pregnancy tests, and confirm the patient's understanding of the teratogenic potential of study drugs;

⁃ Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

⁃ Affiliation to a social security system;

⁃ Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.