mDCF + Avelumab in Resectable Esophago-gastric Adenocarcinoma (EGA)

Inclusion Criteria:

1. Signed, informed consent;

2. Age 18 years or older;

3. Histological diagnosis of adenocarcinoma or poorly differentiated carcinoma of thestomach, esophagogastric junction (EGJ), or lower third of the esophagus;

4. The tumour must be deemed by the team to be potentially resectable. This includesimaging studies (detailed below) to clinically stage the tumor and rule out thepresence of metastatic disease, and includes a preoperative laparoscopic evaluationfor gastric tumors only;

5. Stage IB (TlNl only), II, IHA, IIIB;

6. Life expectancy greater than 3 months;

7. ECOG performance status of 0-1;

8. Neutrophils ~ 1500/μL;

9. Platelet count~ 100,000/μL;

10. Hemoglobin~ 9 g/dL;

11. Total bilirubin level :S 1.5 x the upper limit of normal (ULN) range unless consistentwith Gilbert's syndrome (normal direct bilirubin);

12. AST and ALT :S 2.5 x ULN;

13. If serum creatinine above upper limit of normal (ULN), creatinine clearance ~ 60ml/min as determined by 24-h creatinine clearance or Cockcroft-Gault formula;

14. Negative pregnancy test for women of child-bearing potential; and

15. Highly effective contraception for both male and female subjects throughout the studyand for at least 60 days after last avelumab treatment administration if the risk ofconception exists.

Exclusion Criteria:

1. Current or prior use of immunosuppressive medication, including corticosteroids,within 7 days prior to registration EXCEPT for the following:

2. intranasal, intra-ocular, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection);

3. Systemic corticosteroids at physiologic doses :S 10 mg/day of prednisone orequivalent;

4. Steroids as premedication for hypersensitivity reactions (e.g., CT scanpremedication);

5. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatoryagent. However, patients with diabetes type I, vitiligo, psoriasis, hypo- orhyperthyroid disease not requiring immunosuppressive treatment are eligible;

6. Prior organ transplantation, including allogeneic stem cell transplantation;

7. Squamous-cell carcinoma diagnosis;

8. Significant acute or chronic active infections requiring systemic therapy, including,among others:

9. Known history of testing positive test for human immunodeficiency virus (HIV) orknown acquired immunodeficiency syndrome (AIDS);

10. Positive test for HBV surface antigen and I or confirmatory HCV RNA (if anti-HCVantibody tested positive);

11. Vaccination with live vaccines within 4 weeks of the first dose of avelumab and whileon trial;

12. Known severe hypersensitivity reactions to monoclonal antibodies (Grade 2: 3 NCI CTCAEv 4.03) or to any component in avelumab's formulation, any history of anaphylaxis, oruncontrolled asthma (that is, 3 or more features of partially controlled asthma);

13. Known severe hypersensitivity reaction to cisplatin, docetaxel, 5-FU or drugsformulated with polysorbate;

14. Clinically significant (i.e., active) cardiovascular disease: cerebral vascularaccident/stroke (< 6 months prior to enrollment), myocardial infarction(< 6 monthsprior to enrollment), unstable angina, congestive heart failure (2: New York HeartAssociation Classification Class II), or serious cardiac arrhythmia requiringmedication;

15. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade> 1 ); however,alopecia, sensory neuropathy Grade :S 2, or other Grade :S 2 not constituting a safetyrisk based on investigator's judgment are acceptable;

16. Other severe acute or chronic medical conditions including colitis, inflammatory boweldisease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratoryabnormalities that may increase the risk associated with study participation or studytreatment administration or may interfere with the interpretation of study resultsand, in the judgment of the investigator, would make the patient inappropriate forentry into this study;

17. Known alcohol or drug abuse;

18. Prior systemic therapy for gastric cancer;

19. Prior exposure to antibodies directed at PD-1, PD-L 1, CTLA 4 antigens;

20. Pre-existing medical conditions precluding treatment, including any contraindicationfor major surgery;

21. Pregnancy or lactating mothers. Women of childbearing age must use contraceptionduring and for 3 months following treatment;

22. ECOG performance status of 2 or higher;

23. Significant hearing impairment, as judged by the need for or use of a hearing aid. Ifthere is any uncertainty regarding the degree of hearing impairment, an audiogram willbe done. If the audiogram is grossly normal or shows only minor hearing impairment (i.e. not requiring hearing aid), the patient may be enrolled;

24. Unwillingness to undergo investigations and/or treatment as outlined on the study; or

25. Participation to another trial where an investigational drug is being used.

26. History of another malignancy requiring treatment within the last 3 years. Exceptionsinclude basal cell carcinoma of the skin, squamous cell carcinoma of the skin treatedcuratively and in-situ cervical cancer.