This is a study of Camrelizumab in Combination With concurrent radiotherapy and SOX for Initial Unresectable or potentially resectable proximal Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. Patients without prior palliative therapy will be treated with Camrelizumab, radiotherapy (total 45 Gy), Oxaliplatin, and S-1. The primary endpoint is the 1-year PFS rate.

The purpose of this study is to evaluate the efficacy and safety of Camrelizumab plus Concomitant Chemoradiotherapy in patients with Initial Unresectable or potentially resectable proximal Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. 33 participants with Initial Unresectable locally advanced proximal gastric carcinoma /Gastroesophageal Junction (GEJ) Adenocarcinoma (Siewert type II/III) will be treated with conversion therapy as below once recruited:

1. induction chemotherapy (3w): one cycle of camrelizumab 200mg q3w and SOX regimen (oxaliplatin 130mg/m2, d1, Q3w + S-1 40-60mg bid, d1-d14,Q3w);
2. after the induction, concurrent Chemoradiotherapy will be started (5-6w): intensity modulated radiotherapy was given for tumors and high-risk lymphatic drainage areas, total dose:45Gy/25d, 1.8Gy/d, camrelizumab 200mg q3w, S-1 40-60mg bid, d1-d14, Q3w. The resectability assessment will be performed followed by MDT.
3. Participants still unresectable will receive additional conversion therapy with camrelizumab and SOX regimen. The resectability will be evaluated every 6 weeks until resectable or up to 8 cycles of conversion therapy.

Resectable patients will receive D2 resection.

Inclusion Criteria:

• Patients who provided written informed consent to be subjects in this trial.
• 18-75 years old.
• Has histologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
• The initial unresectable or potentially resectable locally advanced proximal gastric carcinoma /Gastroesophageal Junction (GEJ) Adenocarcinoma (Siewert type II/III) in clinical stage T3-4N+M0 (AJCC 8 edition TNM stage) under any following condition: serious primary tumor invasion, unresectable bulky lymph node, retroperitoneal lymph node metastasis (RPLM). Clinical staging was performed according to enhanced CT/MRI examination.
• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (include but not limited to surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy)
• Plan to have surgery after conversion therapy.
• Patients capable of taking oral medication.
• Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Survival expectation ≥12 months.
• Adequate organ function according to the following laboratory test results: absolute neutrophil count (ANC) ≥1.5×109/L; platelets ≥80×109/L; hemoglobin ≥90g/L; total bilirubin ≤1.5 ULN; serum creatinine ≤1.5 ULN or measured or calculated creatinine clearance > 50ml/min.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication and must be willing to use an adequate method of contraception for the course of the study through 90 days after the last dose of study medication. Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.

Exclusion Criteria:

• HER2 positive subjects will be excluded.
• With evidence of abdominal metastases.
• Has a known additional malignancy that is progressing within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
• The presence of any of the following cardiac clinical symptoms or diseases: New York Heart Association (NYHA) congestive heart failure of grade II or above, LVEF<50%, unstable angina pectoris, myocardial infarction within the past 12 months, QTc ≥ 450ms for male, QTc ≥ 450ms for female, electrocardiogram (ECG) examination revealed clinically significant abnormalities, have factors that increase the risk of prolonged QTc and abnormal heart rhythm.
• With active infection requiring drug intervention (e.g. anti-bacterial drugs, antiviral drugs, antifungal drugs treatment).
• Patients with active hepatitis B (HBsAg positive and HBV DNA≥500 IU/ml), hepatitis C (HCV antibodies positive and HCV RNA copies > ULN)
• With congenital immune deficiency or human immunodeficiency virus (HIV) infection.
• Plan to receive or have previously received an organ or allogeneic bone marrow transplant.
• Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, pulmonary function damaged seriously etc; active tuberculosis (TB).
• Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease.
• Who has received immunosuppressants/systemic corticosteroids therapy < 7 days before the first dose for an immunosuppression purpose (> 10mg/day prednisone or other equivalency drugs).
• Has received a live vaccine within 28 days prior to the first dose, plan to receive a live vaccine during or within 60 days after study treatment.
• Have any contraindications for study treatment.
• Participate in other clinical trials within 4 weeks before the first dose.
• Is pregnant or breastfeeding.
• Patients were judged unsuitable as subjects of this trial by investigators.