Durvalumab With Carboplatin and Etoposide Chemotherapy in Pulmonary Large-cell Neuroendocrine Carcinoma (LCNEC)

Inclusion Criteria: * 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 and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. * Age ≥18 years at the time of study entry * Histologically or cytologically (cell blocks only; smears are not acceptable) documented pulmonary large-cell neuroendocrine carcinoma (LCNEC) * Stage IV disease or unresectable stage IIIB, which cannot be safely encompassed in a single RT field (e.g. supraclavicular N3, T4 by infiltration of vertebral body), according to the AJCC 8th edition Cancer Staging Manual * Body weight \>30 kg * No prior chemotherapy or treatment with another systemic anti-cancer agent. Patients who have received prior chemoradiotherapy for locally advanced pulmonary LCNEC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months from last chemotherapy, radiotherapy or chemoradiotherapy cycle to disease relapse, progression, or diagnosis of metastatic LCNEC. In this case, all toxicity from previous treatments should be resolved and no cumulative toxicity of grade \>1 should be present (see also Section 4.2 "Exclusion criteria"). * No need for concomitant chest irradiation * ECOG performance status 0-1 * Life expectancy ≥ 12 weeks * At least one lesion measurable according to RECIST v 1.1 outside of the CNS, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements * Adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1500/µL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/µL. * Adequate hepatic and renal functions: * Total bilirubin \< 1.5 times the upper limits of normal \[ULN\] * 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 * Serum creatinine ≤1.5 times the ULN or creatinine clearance, calculated according to the formula of Cockcroft and Gault \> 60 ml/min * The patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) \< 1.5 x ULN.). Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0. * Female patients must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: * Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments * Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation * For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form of contraception that results in a low failure rate (\< 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of chemotherapy or 90 days after the last dose of durvalumab, whichever occurs last. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, and vasectomized partner (on the understanding that this is the only one partner during the whole study duration). * Male patients who are sexually active must be willing to use barrier contraceptives (i.e., by use of condoms) during sex with all partners during treatment with chemotherapy and for at least 6 months after the final dose of chemotherapy or 90 days after the last dose of durvalumab, whichever occurs last, to avoid exposing the embryo. Men must refrain from donating sperm during this same period * Ability to comply with the study protocol, in the investigator's judgment Exclusion Criteria: * Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to randomization) requiring immediate radiotherapy for palliation. Patients with asymptomatic CNS lesions are eligible, provided that all of the following criteria are met: * The patient has no history of intracranial hemorrhage, spinal cord hemorrhage or hemorrhagic intracranial lesions * At least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment, or at least 28 days between neurosurgical resection and initiation of study treatment * The patient is on a dose of corticosteroids ≤ 10 mg of oral prednisone or equivalent; anticonvulsant therapy at a stable dose is permitted * Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord) * There is no evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment * History of leptomeningeal disease * Uncontrolled pleural e