Tremelimumab e durvalumab per la gestione non operatoria (NOM) del GC/GEJC resecabile MSI-high.

Inclusion Criteria:

1. Written informed consent and any locally required authorization (such as the European Union [EU] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Age ≥ 18 years old.
3. ECOG Performance Status 0-1.
4. Body weight >30 kg.
5. Diagnosis of resectable gastric or gastroesophageal junction (Siewert II-III) cancer, categorized according to TNM classification 8th edition:

   * cT ≥ 2, any cN, M0
   * Any cT, cN1-3, M0
6. Absence of distant metastases as defined by negativity of computed tomography (CT) and 18-fluorodeoxyglucose positron-emission tomography (18-FDG PET).
7. Life expectancy of at least 12 weeks
8. MSI-high status confirmed by IHC and multiplex PCR, and EBV-negative status by ISH, as determined centrally at the Co-ordinating Centre. Lack of heterogeneity of dMMR status as showed by lack of tumor cells showing concomitant expression of all 4 protein markers.
9. Adequate bone marrow and organ function, as defined by laboratory tests:

   1. Neutrophil count ≥ 1.5 x 10\^3/μL
   2. Platelet count ≥ 100 x 10\^6/μL
   3. Haemoglobin ≥ 9 g/dL
   4. Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values
   5. AST (SGOT) and/or ALT (SGPT) < 2.5 x ULN
   6. Creatinine clearance (calculated according to Cockroft and Gault) > 40 mL/min or serum creatinine < 1.5 x ULN.
10. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating Centre.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Previous enrolment in the present study
3. Participation in another clinical study with an investigational product during the last 12 months
4. Signs of distant metastases.
5. Prior medical treatments or irradiation for gastric cancer.
6. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
7. Previous treatments with immune checkpoint inhibitors targeting CTLA4, including tremelimumab, PD-1 or PD-L1, including durvalumab.
8. History of allergy or severe hypersensitivity reaction to monoclonal antibodies.
9. History of autoimmune diseases or history of organ transplantation that require immunosuppressive therapy. The following are exceptions to this criterion:

   * Patients with vitiligo or alopecia
   * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
   * Any chronic skin condition that does not require systemic therapy
   * Patients with celiac disease controlled by diet alone
10. History of active primary immunodeficiency. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
11. Any condition requiring systemic treatment with corticosteroids at doses equal or superior to 10 mg daily of prednisone or equivalents, or other immunosuppressive drugs within 14 days from the inclusion in the study. The following medications are exceptions to this criterion:

    * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
    * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
    * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
12. Administration of live vaccines within 4 weeks from the inclusion in the study. Note: Patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s).
13. History of allogenic organ transplantation
14. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
15. Women in pregnancy or lactation condition. Women with child-bearing potential or sexually-active men not willing to use adequate contraception during the whole study period.
16. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.