Trial of Neoadjuvant Durvalumab Plus Docetaxel, Oxaliplatin, S-1 Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient Gastric or Gastroesophageal Junction Adenocarcinoma

Inclusion Criteria:

1. Newly diagnosed pathologically proven potentially resectable gastric or GEJadenocarcinoma
2. Clinical stages of T3-4N0 or T2-4N+ according to the American Joint Committee onCancer (AJCC) 8th edition by computed tomography (CT)
3. Microsatellite-instability (MSI) status determined by immunohistochemical (IHC)staining
4. No peritoneal seeding identified by laparoscopy if suspected by CT
5. Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol. Written informed consent and any locally required authorization obtainedfrom the patient/legal representative prior to performing any protocol-relatedprocedures, including screening evaluations
6. Age > 18 years at time of study entry
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Life expectancy of > 12 months
9. Body weight > 30kg
10. No existing neuropathy
11. Adequate normal organ and marrow function as defined below:

• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)
• Platelet count ≥100 (or 75) x 109/L (>75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional ULN
• Measured creatinine clearance (CL) > 40 mL/min or Calculated creatinine CL>40mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hoururine collection for determination of creatinine clearance:

12. Evidence of post-menopausal status or negative urinary or serum pregnancy test forfemale pre-menopausal patients. Women will be considered post-menopausal if they havebeen amenorrheic for 12 months without an alternative medical cause.
13. Patient is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations including followup

Exclusion Criteria:

1. Participation in another clinical study with an investigational product during thelast 2 weeks
2. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of aninterventional study
3. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancertreatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g.,hormone replacementtherapy) is acceptable
4. Major surgical procedure within 28 days prior to the first dose of durvalumab
5. Distant metastasis including M1 lymph node
6. Unable to take medication orally
7. Gastric outlet obstruction and/or severe gastrointestinal bleeding
8. Impaired bowel absorption, including any of the following:

• Bowel obstruction
• Chronic inflammatory bowel disease
• History of extended bowel resection
• Gastric dumping syndrome

9. History of allogenic organ transplantation
10. Active or prior documented autoimmune or inflammatory disorders (includinginflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [withthe exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoidarthritis, hypophysitis, uveitis, etc]). The following are exceptions to thiscriterion:

• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable onhormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but onlyafter consultation with the study physician
• Patients with celiac disease controlled by diet alone

11. Uncontrolled intercurrent illness, including but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, uncontrolled hypertension, unstableangina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronicgastrointestinal conditions associated with diarrhea, or psychiatric illness/socialsituations that would limit compliance with study requirement, substantially increaserisk of incurring adverse events (AEs) or compromise the ability of the patient togive written informed consent
12. History of another primary malignancy except for

• Malignancy treated with curative intent and with no known active disease ≥ 5years before the first dose of durvalumab and of low potential risk forrecurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidenceof disease
• Adequately treated carcinoma in situ without evidence of disease

13. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 mscalculated from 3 ECGs (within 15 minutes at 5 minutes apart)
14. History of active primary immunodeficiency
15. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and TB testing in line withlocal practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patientswith a past or resolved HBV infection (defined as the presence of hepatitis B coreantibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive forhepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negativefor HCV RNA.
16. Current or prior use of immunosuppressive medication within 14 days before the firstdose of durvalumab. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofprednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scanpremedication)

17. Receipt of live attenuated vaccine within 30 days prior to the first dose ofdurvalumab. Note: Patients, if enrolled, should not receive live vaccine whilstreceiving durvalumab and up to 30 days after the last dose of durvalumab
18. Female patients who are pregnant or breastfeeding or male or female patients ofreproductive potential who are not willing to employ effective birth control fromscreening to 90 days after the last dose of durvalumab
19. Known allergy or hypersensitivity to any of the study drugs or any of the study drugexcipients
20. Prior randomisation or treatment in a previous durvalumab or tremelimumab clinicalstudy regardless of treatment arm assignment