sFOLFOXIRI in Advanced Gastroesophageal Cancer, (SAGE)

Inclusion Criteria:

* Histologically and/or cytologically confirmed metastatic or unresectable adenocarcinoma of esophageal, gastroesophageal junction or gastric origin
* Tumor is HER2 negative by standard local testing methodology
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 - 2
* Measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1
* No prior systemic therapy for the present cancer given in the metastatic setting and \> 6 months from administration of peri-operative chemotherapy, if applicable

  o Note: up to two prior cycles of mFOLFOX6 for the present illness is permitted if patients otherwise qualify for the study with adequate baseline imaging
* At least 18 years of age
* Adequate bone marrow and organ functions as defined by:
* Absolute neutrophil count ≥ 1500 cells/ μL
* Hemoglobin ≥ 8 g/ dL
* Platelets \> 100,000 / μL
* Creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance ≥ 30 mL/min by Cockroft-Gault
* Total bilirubin ≤ ULN
* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) \< 2.5 x ULN, unless with liver metastases and then must be \<5 x ULN of normal
* Women and men of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect pregnancy on study, she must notify her treating physician immediately.
* Ability to understand the nature of this study protocol and give written informed consent.
* Willingness and ability to comply with scheduled visits, treatment plans laboratory tests and other study procedures.

Exclusion Criteria:

* Receipt of any investigational agents at the time of registration
* Known, untreated brain metastases
* Grade two or greater peripheral neuropathy
* Presence of any additional active malignancy within the past three years where the malignancy is at least reasonably likely to later the course of therapy, require systemic therapy or interfere with imaging assessments
* For those patients who are going to receive nivolumab
* No active use of systemic corticosteroids at the time of enrollment, at a dose equivalent of 10 mg/day or prednisone
* Clinically significant autoimmune disease which is active or has required systemic immunosuppression within the last two years
* Prior organ transplant or bone marrow transplant
* History of interstitial lung disease or pneumonitis
* Uncontrolled intercurrent illness, including significant active infection, symptomatic congestive heart failure, unstable angina or active arrhythmia
* Major surgery within the four weeks prior to initiation of study treatment
* A history of allergy or hypersensitivity to any of the study drugs
* Any additional significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from fully participating in the study