Avelumab Treatment in Patients With Neuroendocrine Carcinomas (NEC G3) Progressive After Chemotherapy

Inclusion Criteria: * Male or female subjects aged ≥ 18 years * Histologically proven neuroendocrine neoplasia NEC G3 (WHO 2010) * One block or 20 slides (cut at 4 microns) of archival tumor tissue, if available, to perform biomarker assessment * No curative option available * Progressive disease within 9 months before study Initiation and after at least one chemotherapy (platinum based chemotherapy or STZ/TEM/DTIC based chemotherapy in NET G3) * Presence of measurable disease as per RECIST1.1 criteria * Physiologic function: * Hematologic: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused) * Hepatic: total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 × ULN for subjects with documented metastatic disease to the liver) * Renal: estimated creatinine clearance ≥ 60 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) * Pregnancy and contraception: * Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential. * Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days for female and 90 days for male patients after avelumab treatment if the risk of conception exists. * ECOG Performance Status 0 - 2 * Written informed consent: Signed and dated informed consent of the subject must be available before start of any specific trial procedures * Ability of subject to understand nature, importance and individual consequences of clinical trial. Exclusion Criteria: * Merkel Cell carcinoma (MCC) or small cell lung cancer (SCLC) * Typical or Atypical Carcinoid of the lung with a Ki67 \< 20% * Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) * Neuroendocrine tumors that are potentially curable by surgery * Major surgery within 4 weeks of initiation of study medication. * TACE, TAE, SIRT or PRRT within 3 months of starting study treatment * Patients pretreated with Interferon as last treatment line prior to study entry * Concurrent anticancer treatment after the start of trial treatment (e.g., cyto-reductive therapy, TKI therapy, mTOR inhibitor therapy, radiotherapy \[with the exception of palliative radiotherapy\], immune therapy, or cytokine therapy except for erythropoietin or use of any investigational drug). * Immunosuppressants: Current use of immunosuppressive medication, EXCEPT for the following: 1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); 2. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; 3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) * Prior organ transplantation, including allogeneic stem cell transplantation * Active infection requiring systemic therapy * HIV/AIDS: Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Hepatitis: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) * Autoimmune disease: Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. * Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable * Pregnancy or lactation * Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. * Vaccination: Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines * Hypersensitivity to study drug: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3). * Cardiovascular disease: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Participation in other clinical trials during the present clinical trial or within the last 30 days or five terminal phase half-lives of the drug whichever is longer, prior to baseline (this also includes investigational formulation of market products). * Medical or psychological conditions that would jeopardise an adequate and orderly completion of the trial. * Patients, who are legally institutionalized