Synergistic Effects of PD-1 Antibody and Chemotherapy/Targeted Therapy Followed by Surgery-centric Local Treatment in Patients With Limited-metastatic Gastric Cancer

Inclusion Criteria:

1. Men or women aged 18-79.
2. Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (Siewert II or III only) with known PD-L1 expression status.
3. Gastric cancer with proficient mismatch repair (pMMR) or microsatellite stability (MSS) as determined by immunohistochemistry or NCI-recommended microsatellite markers.
4. Primary gastric cancer lesions are resectable, with limited distant metastases meeting the either of the following criteria: (1) condition (a) only; (2) any single condition from (b), with or without (a).

   (a) Non-regional intra-abdominal lymph node metastasis: Include metastasis to the superior mesenteric artery, middle colic artery, and para-aortic/retroperitoneal nodes (according to AJCC 8th edition standards).

   (b1) Localized peritoneal metastasis: P0CY1, P1a, or P1b, according to the Japanese Classification of Gastric Carcinoma (15th edition).

   (b2) Liver metastasis: Up to 5 metastatic lesions. (b3) Lung metastasis: Up to 5 unilateral metastatic lesions. (b4) Ovarian metastasis: Unilateral or bilateral. (b5) Adrenal metastasis: Unilateral or bilateral. (b6) Single-region extra-abdominal lymph node metastasis: Such as cervical, supraclavicular, or mediastinal lymph nodes.

   (b7) Bone metastasis limited to a single radiation field. (b8) Other limited metastases as determined by the research team.
5. No previous anti-tumor treatments.
6. ECOG score ≤2, no surgical contraindications.
7. Life expectancy ≥ 3 months.
8. Physical condition and organ function suitable for major abdominal surgery.
9. Willingness and ability to comply with the study protocol.
10. Fertile women with a negative urine or serum pregnancy test and agreement to use effective contraception during the study and for 180 days after the last dose. Non-sterilized men must also agree to use effective contraception.
11. Signed informed consent with an understanding that patients can withdraw anytime.

Exclusion Criteria:

1. Inability to tolerate oral chemotherapy.
2. Primary gastric lesion confined to the mucosa or submucosa with isolated ovarian metastasis.
3. Central nervous system metastasis and/or carcinomatous meningitis.
4. Allergy to any components of the study medication.
5. History of previous malignancies or concurrent other malignancies, with the exception of completely resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, and other tumors with no recurrence for at least 5 years.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites.
7. Weight loss ≥20% within two months before enrollment.
8. Upper gastrointestinal obstruction or physiological dysfunction.
9. Previous cytotoxic chemotherapy, radiotherapy, immunotherapy, or curative surgery.
10. Prior PD-1/PD-L1/PD-L2 or other T-cell-targeting therapy.
11. Systemic steroid or immunosuppressant use within 14 days before enrollment.
12. Live vaccine within four weeks prior to enrollment.
13. Uncontrolled systemic disease.
14. Active or past autoimmune diseases that may recur.
15. Severe chronic infections or active infections requiring systemic antibacterial, antifungal, or antiviral treatment.
16. History of lung disease.
17. Pregnancy, lactation, or planning for pregnancy.
18. HBsAg-positive with HBV DNA ≥500 IU/mL.
19. Positive HIV antibody.
20. Conditions that may impact study compliance or participation.