Overview

The purpose of this study is to evaluate the efficacy and safety of perioperative Disitamab Vedotin plus Toripalimab and XELOX versus Disitamab Vedotin plus Toripalimab versus XELOX in subjects with HER2-expressing resectable locally advanced gastric or gastroesophageal junction adenocarcinoma.

Eligibility

Inclusion Criteria:

1. Voluntarily participate and sign the informed consent form;
2. Male or female, ≥18 years;
3. Patients with gastric or gastroesophageal junction adenocarcinoma confirmed by histopathology;
4. Clinical stage cT3-4aN+, no distant metastasis (M0);
5. According to the baseline imaging and medical history data evaluated by the Investigators, radical surgery for gastric cancer and R0 resection is expected; Subjects had not previously received any antitumor therapy for gastric or gastroesophageal junction adenocarcinoma;
6. HER2- expression: IHC 1+, 2+, 3+;
7. ECOG performance status score of 0 or 1;
8. Cardiac function: left ventricular ejection fraction ≥50%;
9. The following criteria should be met within 7 days prior to study dosing (normal values are based on the clinical trial center):

   9.1Bone marrow function:

   1. absolute neutrophil count (ANC) ≥1.5×109/L (no treatment with granulocyte colony-stimulating factor within 1 week prior to examination);
   2. Platelets ≥100×109/L (platelets should not be transfused within 1 week before the examination, and recombinant human thrombopoietin therapy should not be used within 2 weeks)
   3. hemoglobin ≥9g/dL (blood transfusion and erythropoietin treatment are not allowed within 2 weeks prior to the examination);

9.2Liver function:

1. Serum total bilirubin ≤1.5 times the upper limit of normal (ULN);
2. alanine amino transferase (ALT) and aspartate amino transferase (AST) ≤2.5 × ULN;

9.3 Kidney function:

             a.Blood creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min according to
             Cockcroft-Gault formula method; Female: CrCl= (140-age) × weight (kg) × 0.85 72 ×
             serum creatinine (mg/dL) Male: CrCl= (140-age) × weight (kg) × 1.00 72 × serum
             creatinine (mg/dL)
             9.4 Coagulation function:
               1. prothrombin time (PT) ≤1.5×ULN;
               2. thrombin time (TT) ≤ 1.5×ULN;
               3. activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
         10. Female subjects should be surgically sterilized, postmenopausal, or agree to use at
             least one medically acceptable method of contraception (e.g., intrauterine device,
             contraceptives, or condoms) for 7 days before the first dose and for 6 months after
             the end of the study treatment period, and not breastfeed. Blood pregnancy tests must
             be negative within 7 days prior to study enrollment. Male subjects should agree to use
             at least one medically approved contraceptive method (e.g., condoms, abstinence, etc.)
             for 7 days prior to initial dosing and up to 6 months after the end of the study
             treatment period;
         11. Able to understand trial requirements, willing and able to follow trial and follow-up
             procedures.
        Exclusion Criteria:
          1. Received any anti-tumor therapy for gastric or gastroesophageal junction
             adenocarcinoma before study dosing, including chemotherapy, radiotherapy, targeted
             therapy, immunotherapy and other anti-tumor drug therapy (including Chinese medicine
             treatment with anti-tumor ingredients specified in the instructions within 2 weeks
             before screening);
          2. The investigators considered perioperative period treatment of patients requiring
             radiotherapy for target lesions；
          3. Major surgery was performed within 4 weeks before the start of study dosing and did
             not fully recover;
          4. Patients with active gastrointestinal bleeding or high risk of bleeding within 2 weeks
             prior to screening;
          5. Gastrointestinal perforation/fistula 6 months before screening;
          6. Upper digestive tract obstruction that cannot guarantee drug absorption, functional
             abnormalities or malabsorption syndrome, which can affect the absorption of
             capecitabine ;
          7. Peripheral polyneuropathy ≥ NCI Ⅱ grade；
          8. Serum virology examination (based on the normal value of the research center):
               -  Positive HBsAg test with positive HBV DNA copy number;
               -  Positive HCVAb test with positive HCV RNA PCR test.
               -  Positive HIVAb test.
          9. Have received live vaccine within 4 weeks prior to screening or plan to receive any
             vaccine during the study period (except for the novel coronavirus vaccine);
         10. Heart failure rated 3 or higher by the New York College of Cardiology (NYHA);
         11. Cardiac chest pain, defined as moderate pain that restricts daily activities, occurred
             within 28 days prior to screening. There were serious arteriovenous thrombosis events
             or cardiovascular and cerebrovascular accidents within six months before dosing, such
             as deep vein thrombosis (except asymptomatic and untreated intermuscular venous
             thrombosis), pulmonary embolism, cerebral infarction, cerebral hemorrhage, and
             myocardial infarction (except asymptomatic lacunar infarction that did not require
             clinical intervention);
         12. There is an active or advanced infection that requires systematic treatment
             (experimental medication may be initiated 2 weeks after the end of anti-infective
             therapy), such as active tuberculosis;
         13. There are systemic diseases that have not been stably controlled which are determined
             by investigators, including diabetes, hypertension, cirrhosis, etc.;
         14. A history of lung disease that requires treatment and has the potential to interfere
             with surgery, including but not limited to interstitial lung disease, non-infectious
             pneumonia, pulmonary fibrosis, and acute lung disease;
         15. Active autoimmune diseases requiring systemic therapy (such as the use of
             disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within 2 years
             prior to dose administration, and replacement therapies (e.g., thyroxine, insulin, or
             physiological replacement of glucocorticoids due to renal or pituitary deficiency) are
             allowed, and a history of refractory autoimmune disease. Systemic use of steroids
             within 14 days prior to screening (dose > 10 mg/day prednisone or equivalent dose of
             other glucocorticoids) or other systemic immunosuppressive therapy;
         16. Other malignancies within 5 years prior to screening, other than those that have been
             cured after treatment (including but not limited to adequately treated thyroid cancer,
             cervical carcinoma in situ, basal or squamous cell skin cancer, or breast ductal
             carcinoma in situ treated with radical surgery);
         17. Previously received allogeneic hematopoietic stem cell transplantation or solid organ
             transplantation;
         18. Allergies to any of the drugs in this study;
         19. Known deficiency of dipyrimidine dehydrogenase (DPD);
         20. Receiving immunotherapy (including but not limited to interleukin, interferon, thymus
             hormone) or other investigational drugs within 28 days prior to screening;
         21. Pregnant or lactating women;
         22. Any other disease, metabolic disorder, or abnormal findings upon physical examination
             or laboratory examination that makes the subject unsuitable for receiving the
             investigational drug, affects the interpretation of study outcomes, or poses risks to
             patient safety, as determined by the investigator;
         23. Subject is assessed to be unable or unwilling to comply with the requirements of the
             protocol.