Randomizowane, kontrolowane badanie skuteczności serplulimabu w skojarzeniu z chemioterapią w leczeniu miejscowo zaawansowanego gruczolakoraka żołądka

Inclusion Criteria:

1. Have a full understanding of the study and voluntarily sign the Informed Consent Form (ICF);
2. The tumor is located in the stomach, pathologically confirmed as adenocarcinoma, with clinical stage III (cT3-4aN1-3M0) determined by enhanced CT/MRI examination;
3. Tumor specimens show PD-L1 positivity (CPS ≥ 1). At the time of enrollment, there must be sufficient tumor tissue available for assessing PD-L1 expression levels (subjects undergoing repeated screening do not need additional PD-L1 testing);
4. No restriction on gender, aged 18-70 years;
5. Generally in good condition, with an ECOG performance status of 0-1, and no contraindications to surgery;
6. Physical condition and organ function allow for major abdominal surgery;
7. Expected survival ≥ 3 months;

8. Laboratory test results within 7 days prior to enrollment must meet the following criteria:

   1. WBC > 3.50 × 10⁹/L and < 9.50 × 10⁹/L, ANC > 1.5 × 10⁹/L, Hb ≥ 80 g/L, PLT ≥ 100 × 10⁹/L;
   2. Serum bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN;
   3. Creatinine ≤ 1.5 × ULN or serum clearance > 60 ml/min;
   4. INR and aPTT ≤ 1.5 × ULN (for subjects not receiving anticoagulation therapy); subjects receiving anticoagulants must be on a stable dose;
9. Demonstrates good compliance and is able to cooperate with the study protocol's laboratory, auxiliary examinations, and relevant specimen collection;
10. Women of childbearing potential (including those in menopause due to chemotherapy or other medical reasons) must agree to use contraception from the time of signing the ICF to at least 5 months after the last dose of study treatment or concurrent chemotherapy (whichever is later). They must also agree not to breastfeed during this period. Men must agree to use contraception from the initiation of the study drug to at least 7 months after the last dose of study drug or concurrent chemotherapy (whichever is later).

Exclusion Criteria:

1. HER2-positive status, defined as IHC3+ or IHC2+ with FISH+; or known MSI-H/dMMR.
2. Tumor involvement of the esophagogastric junction (EGJ).
3. Known allergy to citric acid monohydrate, sodium citrate dihydrate, mannitol, or polysorbate (components of the investigational drug).
4. History or concurrent diagnosis of other malignancies (excluding completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, mucosal carcinoma, superficial bladder cancer, or any other cancer with no recurrence for at least 5 years).
5. Uncontrolled pericardial effusion, pleural effusion, ascites, gastrointestinal bleeding, or high bleeding risk within 2 weeks prior to enrollment.
6. Weight loss exceeding 20% within 2 weeks prior to enrollment.
7. Inability to take oral medication.
8. History of chemotherapy, radiotherapy, immunotherapy, or surgery for gastric cancer.
9. Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other antibody targeting T-cell co-stimulatory or checkpoint pathways).
10. Tyrosine kinase inhibitor treatment within 2 weeks prior to enrollment.
11. Long-term use of immunosuppressive drugs or systemic/local corticosteroids at immunosuppressive doses (e.g., >10 mg/day prednisone or equivalent).
12. Vaccination with any anti-infective vaccine (e.g., influenza, varicella) within 4 weeks prior to enrollment.
13. Uncontrolled systemic diseases, such as diabetes or hypertension.
14. Current or required anticoagulant therapy (except for low-dose aspirin used as antiplatelet therapy).
15. Active autoimmune diseases or history of autoimmune diseases (e.g., interstitial pneumonitis, uveitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; exceptions include vitiligo or childhood asthma resolved without intervention; patients requiring bronchodilators for asthma are excluded).
16. Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year prior to screening.
17. History of lung diseases confirmed by imaging (preferably CT) or clinical results, such as interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, or acute lung diseases.
18. Contraindications to oxaliplatin, docetaxel, 5-FU, or leucovorin.
19. Pregnant or breastfeeding women, or women who might be pregnant.
20. Active hepatitis.
21. Positive test results for any of the following: HIV-1 antibody, HIV-2 antibody, HTLV-1 antibody, or HCV antibody.
22. Any clinically significant disease or condition deemed by the investigator to affect protocol compliance, the ability to sign the informed consent form (ICF), or suitability for participation in this clinical trial.