Neoadjuvant Toripalimab for dMMR/MSI-H Gastric Cancer

Inclusion Criteria:

1. Aged 18-75 years, regardless of gender 2. Patients with histologically or cytologicallyconfirmed adenocarcinoma of the stomach or gastroesophageal junction and confirmed dMMR orMSI-H 3. Preoperative CT or MRI staging meeting the following criteria: T2 and above, withor without lymph node involvement, without clear distant metastasis 4. ECOG score of 0-1.
2. Expected survival ≥ 2 years. 6. Good organ function (no blood transfusion, nohematopoietic stimulating factor, no albumin or blood product transfusion within 14 daysprior to the examination).
3. Platelet (PLT) count ≥ 90*109/L.
4. Neutrophil count (ANC) ≥ 1.5*109/L.
5. Hemoglobin (Hb) level ≥ 9.0 g/dl.
6. International normalized ratio (INR) ≤ 1.5.
7. Prothrombin time (PT) and active partial thromboplastin time (APTT) ≤ 1.5 x ULN.
8. Glycated hemoglobin (HbA1c) <7.5%.
9. Total bilirubin (TBIL) level ≤ 1.5 times the upper limit of normal (ULN).
10. Alanine amino transaminase (ALT) and aspartate amino transaminase (AST) levels ≤ 2.5 xULN.
11. Serum creatinine (Cr) level ≤ 1.5 x ULN and creatinine clearance ≥ 60 ml/min.
12. Thyrotropin (TSH) ≤ ULN; serum free thyroid hormone (T4) normal; serum freetriiodothyronine (T3) normal; (except for those who have received previous thyroidsurgery or have a history of head and neck radiotherapy)
13. Serum amylase ≤ 1.5 x ULN.
14. Lipase ≤ 1.5×ULN. 7. Women of childbearing age must have a negative pregnancy test andmust use contraception and avoid breastfeeding during the study and for 3 months afterthe last dose; male subjects must agree to use contraception during the study and for 3 months after the last dose.

8.Be able to understand and willing to sign a written informed consent form.

Exclusion Criteria:

1. Previously received chemotherapy, radiotherapy or immunotherapy for gastric cancer
2. Previously diagnosed any other malignancy with a primary site or histological typedifferent from gastric cancer within 5 years prior to study entry, except adequatelytreated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
3. With known hypersensitivity to the study drug or excipients, or to similar drugs
4. Received major surgery or open biopsy, or had a major trauma within 4 weeks prior tothe start of study treatment
5. Received immunosuppressive drugs (excluding inhaled corticosteroids or ≤10 mg/dayprednisone or equivalent pharmacophysiologic doses of other systemic steroids) within 2 weeks prior to the start of study treatment
6. Planned live attenuated vaccination within 4 weeks prior to the start of studytreatment or during the study period
7. Inability to discontinue CYP3A4 inducers or inhibitors within 1 week prior to thestart of study treatment and during the study period
8. Presence of any autoimmune disease or history of autoimmune disease.
9. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or activehepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg positive and HBV-DNA ≥ 2000 IU/ml copies/ml)), or other seriousinfection requiring antibiotics for systemic therapy, or during screening/studyUnexplained temperature >38.5°C prior to the start of treatment.
10. Presence of the following diseases within 6 months prior to the start of studytreatment: myocardial infarction, severe/unstable angina, NYHA class 2 or highercongestive heart failure, poorly controlled arrhythmias, etc.
11. Non-well-controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolicblood pressure ≥ 100 mmHg under optimal treatment)
12. Arterial/venous thrombotic events such as cerebrovascular accidents (transientischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep veinthrombosis, vasculitis, etc. within 3 months prior to the start of study treatment
13. Urine routine suggesting urine protein up to +++ and confirmed 24-hour urine proteinquantification up to 1.0g.
14. The presence of a history of allogeneic organ transplantation or allogeneichematopoietic stem cell transplantation
15. Seizures requiring medication (e.g., steroids or antiepileptic drugs) for treatment.
16. Presence of a history of substance abuse, drug use, or alcohol dependence. Patientswith other serious, acute or chronic medical conditions that may increase the risk ofstudy participation and study medication, or that may interfere with theinterpretation of study results, and who are judged by the investigator to beunsuitable for participation in a clinical trial.