Oxaliplatin ± Nivolumab in Combination With Trifluridine/Tipiracil or 5-fluorouracile in Frail Patients With Advanced, Recurrent or Metastatic Gastric, Oesophageal or Gastroesophageal Junction Cancer

Inclusion Criteria:

1. Histologically confirmed locally advanced, recurrent or metastatic non resectable adenocarcinoma of the stomach, oesophagus or gastroesophageal junction (GEJ) ineligible to curative treatment.
2. No dysphagia or difficulty in swallowing.
3. No overexpression/amplification of HER2 (IHC 0 or 1+; if IHC is 2+, HIS must be negative). Known combined positive scor (CPS) PD-L1 score (result in % with the name of the method used). The microsatellite and mismatch repair (MMR) status of patient's tumour (MSI/MSS and pMMR/dMMR) must also be known at the time of screening (IHC and PCR tests have to be done).
4. At least one evaluable lesion according to RECIST v1.1 outside any previously irradiated area.
5. No prior palliative chemotherapy.
6. Age ≥18 years old.
7. Patient eligible for FOLFOX chemotherapy
8. Adequate organs function:

   * Absolute neutrophils count ≥1.5x10⁹/L
   * Platelets count ≥100x10⁹/L
   * Haemoglobin ≥9 g/L
   * Serum bilirubin levels \<2 times upper limit of normal (ULN), up to 2.5 times ULN in case of hepatic metastasis (biliary drainage allowed)
   * Transaminases \<5 times ULN
   * Creatinine clearance \>40 mL/min
9. No Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia \<16 ng/ml)
10. Women of childbearing potential must have a negative serum or urine pregnancy test done within 14 days before the first study treatment.
11. Patients must agree to use adequate contraception methods for the duration of study treatment and within 6 months after completing treatment.
12. Patients must be affiliated to a Social Security System (or equivalent).
13. Patient must have signed and dated a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
14. Availability of archived tumour material for ancillary studies

Exclusion Criteria:

1. Patient with a performance status ECOG PS \>2.
2. Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin treated by surgery).
3. Adjuvant chemotherapy or radio-chemotherapy completed for less than 6 months.
4. Peripheral neuropathy of NCI-CTCAE grade ≥2 at baseline.
5. Patients with known allergy or severe hypersensitivity to any of the trial drugs or any of the trial drug excipients.
6. Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
7. Previous treatment with trifluridine/tipiracil.
8. Known Human Immunodeficiency Virus (HIV) infection.
9. Active Hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen \[HBsAg\] test prior to inclusion) or hepatitis C virus (HCV).
10. Interstitial lung disease.
11. Prior pneumonitis requiring systemic corticosteroid therapy.
12. Active infections.
13. Pregnant or breastfeeding woman.
14. Participation in another therapeutic trial within the 30 days prior to randomisation.
15. Persons deprived of their liberty or under protective custody or guardianship.
16. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia (for men: QTc ≥450 msec, for women: QTc ≥470 msec)
17. Active systemic autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
18. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease