Clinical Study of Regorafenib and Nivolumab Plus Chemotherapy

Inclusion Criteria: 1. Histologically confirmed gastric/ gastroesophageal junction/esophageal adenocarcinoma that is confirmed to be unresectable/recurrent disease 2. At least 1 measurable lesion as defined by RECIST guideline version 1.1. 3. Age \>= 20 years on the day informed consent is obtained 4. ECOG Performance status (PS) 0 or 1 5. The most recent laboratory value within 14 days prior to enrollment meets all of the following. (Examinations on the same day of the week 2 weeks prior to the day of enrollment may be utilized.) 1)Neutrophils \>= 1,200/mm\^3 2)Hemoglobin \>= 8.0 g/dL 3)Platelets \>= 75,000/mm\^3 4)Total bilirubin \<= 1.5 mg/dL 5)AST (GOT) \<= 100 IU/L If liver metastases are present: \<= 200 IU/L 6)ALT (GPT) \<= 100 IU/L If liver metastases are present: \<= 200 IU/L 7)Creatinine \<= 1.5 mg/dL 8)Urine protein: any of the following (if any of the test criteria are met, other tests may not be performed.) (i)Urine protein (dipstick) \<= 2+ (ii)Urine protein creatinine (UPC) ratio \< 3.5 (iii)Urine protein \<= 3,500 mg for 24-hour collection sample 9)PT-INR: \<= 1.5 (\<= 3.0 if on an anticoagulant) 6. No transfusions within 7 days prior to enrollment. (Transfusions on the same day of the week prior to enrollment are allowed) 7. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment. Both men and women must agree to use adequate contraception from the time of signing the informed consent form for a period of time (9 months in women and 7 months in men) after the last dose of protocol therapy 8. Oral administration is feasible 9. Written informed consent to participate in the study has been obtained from the patient themselves Exclusion Criteria: 1. Prior chemotherapy for unresectable advanced/recurrent gastric/ gastroesophageal junction/esophageal adenocarcinoma (Note: Prior neoadjuvant or adjuvant therapy is allowed. However, treatment must have been completed at least 6 months prior to enrollment and progression must have occurred at least 6 months after the completion of the therapy) 2. HER2 positive (IHC3+, or IHC2+ and FISH positive) 3. Patients with hypertension that is difficult to control (systolic blood pressure \>= 160 mmHg or diastolic blood pressure \>= 90 mmHg) despite multiple antihypertensive medications 4. Patients with a history of acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stent placement within 6 months prior to enrollment 5. Patients with a history or evidence of congestive heart failure of Class III or higher according to the New York Heart Association (NYHA) classification 6. Confirmed metastases to the central nervous system (Confirmation by brain computed tomography scan or magnetic resonance imaging is required at screening only if metastases to the central nervous system are clinically suspected) 7. Active double cancers with intensive treatments and possibly affect continuation of protocol treatment 8. Those with serious (needing inpatient care) complications (intestinal paralysis, intestinal obstruction, pulmonary fibrosis, poorly controlled diabetes mellitus, cardiac failure, myocardial infarction, angina pectoris, renal failure, hepatic failure, psychiatric disease, cerebrovascular disorder, ulcers requiring blood transfusions, etc.) 9. Those with active hepatitis * HBs antigen positive * HBs antibody or HBc antibody positive and HBV-DNA positive * Active hepatitis C (e.g., qualitative detection of HCV RNA) However, those who are HBs antigen positive may be considered eligible if HBV DNA is \<1.3 log IU/mL (\<2.1 log copies/mL) after treatment with antiviral drugs, such as nucleoside analogs. 10. Confirmed HIV infection 11. Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease. Patients with type 1 diabetes mellitus, hypothyroidism which is manageable by hormone replacement, or skin disorders not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia) are permitted to be enrolled. 12. Patients who require treatment with systemic corticosteroids (excluding temporary use for testing or prophylactic administration for allergic reactions, or for reduction of edema associated with radiotherapy), or immunosuppressants, or those treated with any of these therapies within 2 weeks prior to study enrollment 13. Patients who fail to use adequate contraception during the study participation and contraception period 14. Those unwilling or unable to comply with the protocol 15. Those considered by the principal investigator or sub-investigator as ineligible for this investigator-initiated trial