Assessment of Metabolic & Path Response w/ RCT & ImT Before Surgery in Locally Advanced Esoph and Gastro-esoph Jction CA

Inclusion Criteria:

1. Age ≥ 18 years old
2. ECOG performance status ≤ 1
3. Female and Male
4. Must have histologically confirmed esophageal ADC or SCC or gastro-esophageal junction ADC (Siewert I and II) eligible for a curative intent resection (recommended exploration by EUS and diagnostic laparoscopy in gastro-esophageal junctions) without restriction in age and sex and candidate for neoadjuvant RCT.
5. At least classified clinical T3Nx or any T, N+ according to cTNM version 7.
6. Negative serum pregnancy test (for women of childbearing potential) within 7 (+/-1) days prior to the beginning of treatment.
7. Women of childbearing potential must agree to use one highly effective method of contraception at study entry (if this is not already the case, put in place within 1 week after ICF signature, and at the very latest before 1st administration of study treatment), during the study treatment administration and at least 5 months after the last administration of study treatment.
8. Men must agree to use condom during the course of this study and for at least 5 months after the last administration of the study treatment.
9. Adequate bone marrow function as defined below:

   * Absolute neutrophil count ≥1500/µL or 1.5x109/L
   * Hemoglobin ≥ 9 g/dL
   * Platelets ≥100000/µL or 100x109/L
10. Adequate liver function as defined below:

    * Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome \< 3xUNL is allowed
    * AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN
    * Alkaline phosphatase ≤ 2.5 x ULN
11. Adequate renal function as defined:

    * Creatinine ≤ 1.5 x UNL or creatinine clearance \>60 mL/min
12. Participants must have normal cardiac and pulmonary functions defined with ultrasonography (LVEF\>50%) and pulmonary function tests (including DLCO (diffusing capacity factor of the lung for carbon monoxide)).
13. Completion of all necessary screening procedures within 28 days prior to enrolment.
14. Accessible tumour for biopsies through upper gastro-intestinal endoscopy (for translational research activities).
15. Signed Informed Consent form (ICF) obtained prior to any study related procedure and study treatment.
16. For the phase II expansion cohort only, significant FDG uptake at the primary tumour on baseline PET/CT, performed not more than 7 days before the beginning of the first course of CT, defined as SUVmax \> 2x the mean liver uptake.

Exclusion Criteria:

Subjects meeting one of the following criteria are not eligible for this study:

1. Patient ineligible for curative intent surgery:

   * T4 with involvement of mediastinal structures as tracheobronchial, recurrent nerve, aorta over 90° of its circumference, vertebral body
   * Tumour ≥ 4cm in diameter developed above the carina
   * Visceral metastasis
   * Metastatic lymph nodes: supraclavicular and/or lombo-aortic
   * Cervical esophageal cancer defined as a tumor involving the lower border of the cricoid cartilage (at the level of the sixth cervical vertebra) to the thoracic inlet 5cm down under, generally between 18 and 20 cm from the dental arcade
2. Uncontrolled concurrent illness or any significant disease that, in the investigator's opinion, would exclude the patient from the study.
3. Absolute contraindication for surgery: respiratory failure (VEMS \< 1000mL), weight loss\> 20%, renal failure: creatinine \> 1.5 ULN, myocardial infarct \< 6 months, evolutive cardiopathy, ECOG 3 and 4, non-compensated cirrhosis.
4. Pregnant and/or lactating women.
5. Uncontrolled diabetes.
6. Individuals with a history of a different malignancy within the last 5 years are ineligible except cervical cancer in situ, and early stage basal cell or squamous cell carcinoma of the skin.
7. Patients with active, known or suspected autoimmune disease or condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive systemic treatment.

   * (Exception: patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring immunosuppressive systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to be enrolled.
   * Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active/autoimmune disease.
8. Patients with diseases known for hypersensitivity to radiotherapy.
9. Prior treatment for esophageal cancer: surgery, radiotherapy, chemotherapy or immunotherapy (in particular but not limited to anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumour vaccines or other immuno-stimulatory anti-tumour agents.
10. Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (ribonucleic acid or HCV antibody) indicating acute or chronic infection.
11. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
12. History of allergy to study drug components or excipients.
13. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.