First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer

Inclusion Criteria: 1. Patients must have dated and signed an approved written informed consent form. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care. 2. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study, Target Population 3. Inoperable, advanced, or metastatic gastric cancer or gastroesophageal junction or distal esophageal carcinoma and histologically confirmed predominant adenocarcinoma, 4. Expression of PD-L1 with a combined positive score (PD-L1 CPS) ≥5, Note: information must be available at the time of inclusion, the examination will be performed locally in the center and secondarily confirmed centrally, 5. No prior systemic cancer treatment given as primary therapy for advanced nonresectable or metastatic disease, Note: if patient received neoadjuvant/adjuvant therapy, this therapy should be completed at least 6 months prior to the diagnosis of metastatic or recurrent disease is made. Palliative radiotherapy is allowed and must be completed 2 weeks prior to randomization, 6. At least one measurable lesion as assessed by computed tomography (CT)-scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and feasibility of repeated radiological assessments; radiographic tumor assessment should be performed within 28 days prior to randomization, 7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, 8. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization of study treatment: 1. White blood cell ≥ 2000/μL; 2. Neutrophils ≥ 2000/μL; 3. Platelets ≥ 100.000/μL; 4. Hemoglobin ≥ 9.0 g/dL; 5. Serum albumin ≥ 30 g/L; 6. Serum creatinine level ≤ 150 μM and calculated creatinine clearance (Cockcroft-Gault) \> 50 mL/minute, 7. Total bilirubin ≤ 1.5 x upper normal limit (ULN); 8. Alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver metastases are present); 9. Aspartame aminotransferase (AST) ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver metastases are present); 10. Potassium ≥ 1.0 x lower limit of normal (LLN), 11. Magnesium ≥ 1.0 x LLN, 12. Calcium ≥ 1.0 x LLN, 9. Baseline-corrected QT interval ≤ 450 msec for males and ≤ 470 msec for females, 10. Availability of a representative tumor tissue specimen for exploratory translational research; tumor tissue samples, either formalin- fixed paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections (minimum of 20 positively charged slides) from primary or metastatic site must be submitted to the central laboratory, 11. Registration in a national health care system (PUMa-Protection Universelle Maladie included. Age and reproductive status 12. Age ≥ 18 years, 13. Women must not be pregnant, breastfeeding, or expecting to conceive during the study, 14. Reproductive status: 1. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug, 2. WOCBP must agree to use an adequate method of contraception or birth control for the duration of study treatment and 5 months (nivolumab), 9 months (oxaliplatin), 6 months (5-FU) or at least 1 month (EXL01) of the patient's last dose of the study drug, 3. Males who are fertile and sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and 6 months (nivolumab, oxaliplatin, or 5-FU) or at least 1 month (EXL01) after the last dose of study treatment. In addition, males must be willing to refrain from sperm donation during this time, Exclusion Criteria: Target Disease Exceptions 1. Known HER-2 positive status or unknown HER-2 status before inclusion, 2. Active brain metastases or known history of leptomeningeal carcinomatosis, 3. Ascites, which cannot be controlled with appropriate interventions, Exclusion criteria related to medical history and concurrent disease 4. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast, 5. Active, known, or suspected autoimmune disease; type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted, 6. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity, 7. Prior treatment with an anti-PD(L)1, anti-LAG-3, or 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-tumor vaccines or other immuno-stimulatory antitumor agents, 8. Condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days (2 weeks) of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted prior to randomization in the absence of active autoimmune disease, 9. Persistence of toxicity (The National Cancer Institute Common Terminology Criteria for Adverse Event \[NCI CTCAE\] v 5.0) grade \>1 related to prior anticancer treatments, 10. Major surgery within 28 days (4 weeks) prior to first dose of study treatment, Note: Participants who had surgery \>4 weeks prior to screening must have recovered adequately from any toxicity and/or complications from the surgery or trauma prior to starting study intervention. 11. Concomitant unplan