Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage Esophageal Adenocarcinoma With Indication for Radical Surgery

Inclusion Criteria: 1. Patient has given written informed consent. 2. Patient is, in the investigator's judgement, willing and able to comply with the study protocol including the planned surgical treatment. 3. Patient is ≥ 18 years of age at time of signing the written informed consent. 4. Patient has been diagnosed with histologically confirmed esophageal adenocarcinoma (including gastroesophageal junction (GEJ) (Siewert I-III)) with: 1. cT2 N0 M0 stage or T1 N0 M0 stage and a given indication for radical surgical resection to current S3-guidelines (this includes patients with a given indication for radical surgery after endoscopic-resection of a cT1-2 N0 M0 tumor \[poor grading or L1/V1 invasion or basal R1 resection or deep submucosal infiltration\]) (see section 4.2.3 for detailed information). 2. tumor is considered medically and technically resectable. 5. Tumor is tested (local testing with validated assays is sufficient, e.g., Dako PD-L1 IHC 22C3 or 28-8) for PD-L1 according to combined positive score (CPS) and results must be available prior study enrollment. In addition, tumor should be tested locally for MSI status and PD-L1 according to tumor proportion score (TPS) OR a representative tumor specimen that is suitable for central determination of PD-L1 TPS and MSI status is available. The analysis requires paraffin embedded biopsy samples of the tumor to be provided to the Sponsor. NOTE: It is encouraged that CPS, TPS and MSI testing is performed in parallel locally at the trial site prior to enrollment, but at least CPS per local testing has to be available prior to enrollment. 6. Patient has not received prior cytotoxic or targeted therapy. 7. Patient has not had a prior complete esophagogastric tumor resection. 8. Patient has a ECOG ≤ 1. 9. Patient must have life expectancy of at least 12 weeks 10. Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 6 months after the last study treatment if it is in the core treatment phase or for at least 3 months after last study treatment occurred in the maintenance phase. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy. 11. Patient has a body weight \> 30 kg 12. Patient has adequate hematological, hepatic and renal function as indicated by the following parameters: 1. Leukocytes ≥ 3,000/µL, platelets ≥ 100,000/µL without transfusion, absolute neutrophil count (ANC) ≥ 1,500/µL without granulocyte colony-stimulating factor support, hemoglobin ≥ 90 g/L (9 g/dL) - Patients may be transfused to meet this criterion. 2. Bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate transaminase and alanine transaminase ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN 3. Serum creatinine ≤ 1.5 x ULN, or glomerular filtration rate \> 45 mL/min (calculated using the Cockcroft-Gault formula) 4. Serum albumin ≥ 25 g/L (2.5 g/dL) 5. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN; for patients receiving therapeutic anticoagulation: stable anticoagulant regimen 13. Patient has no human immunodeficiency virus (HIV) infection. NOTE: Patient with infection is eligible if he/she meets all the following criteria: 1. CD4 count is ≥350 cells/µL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications 2. Probable long-term survival with HIV if cancer were not present 3. Stable on a highly active antiretroviral therapy (HAART) regimen for ≥4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study 4. HIV is not multi-drug resistant 5. Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication Exclusion Criteria: 1. Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein. 2. Patient has any known contraindication (including hypersensitivity) to docetaxel, 5-FU, leucovorin (calcium folinate), or oxaliplatin. In cases of pernicious anemia or other anemias due to vitamin B 12 deficiency, folinic acid (Leucovorin) is contraindicated and trial inclusion is not possible or only possible after compensation the anaemic status. 3. Patient has a known dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with reduced DPD activity (CPIC activity score of 1.0-1.5) might participate in the study and receive a reduced dosage of 5-FU. 4. Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, or controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible based on consultation with the sponsor's medical monitor. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all following conditions are met: * Rash must cover \< 10% of body surface area. * Disease is well controlled at baseline and requires only low-potency topical corticosteroids. * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months. 5. Patient had a prior allogeneic bone marrow transplantation or prior solid organ transplantation. 6. Patient has a history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis within the radiation field (fibrosis) is permitted. 7. Patient has active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test prior to enrollment) or hepatitis C infection NOTE: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA). 8. Patient has active tuberculosis. 9. Patient has uncontrolled tumor-related pain (Patients requiring pain medication must be on a stable regimen at study entry.) 10. Patient received an administration of a live, attenuated vaccine within four weeks prior to start of enrollment, or anticipation that such a live attenuated vaccine will be required during the study or within 30 days after the last dose of durvalumab. 11. Patient had a prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibodies. 12. Patient had a treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is longer, prior to study enrollment. 13. Patient had a treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed 1. Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra articular injection) 2. Systemic corticosteroids at physiologic dose not to exceed 10mg/day of prednisone or its equivalent 3. Steroids as premedication for hypersensitivity reactions (e.g. CT premedication) 14. Patient has a significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina. 15. Patient has a clinically significant valvular defect. 16. Patient has a history of malignancy other than EGA within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. 17. Patient has peripheral polyneuropathy ≥ NCI CTCAE grade 2. 18. Patient has uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN). 19. Patient has a serious infection requiring oral or IV antibiotics within 14 days prior to study enrollment. 20. Patient has chronic inflammatory bowel disease. 21. Patient has clinically significant active gastrointestinal bleeding. 22. Patient underwent major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment. 23. Patient has evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results. 24. Patient participated in another interventional clinical study ≤ 30 days prior to study enrollment or participation in such a study at the same time as this study. 25. Patient has taken an investigational drug within 28 days prior to initiation of study drug. 26. Female patients, who are pregnant or breast feeding or planning to become pregnant within and 6 months after the end of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.