Mannatide Combined With CAPOX and Tislelizumab for Advanced Gastric Cancer.

Inclusion Criteria:

1. Histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma.
2. Unresectable recurrent or metastatic disease confirmed by imaging and surgical evaluation.
3. Age 18 to 75 years.
4. Expected survival greater than 3 months.
5. No prior systemic therapy for recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma. Previous neoadjuvant or adjuvant therapy is allowed if completed at least 6 months before enrollment without evidence of recurrence or progression.
6. ECOG performance status 0-1.
7. At least one measurable lesion according to RECIST version 1.1.
8. Availability of tumor tissue for PD-L1 testing.
9. Adequate hematologic, hepatic, renal, and coagulation function.
10. Recovery of prior treatment-related toxicities to Grade 0-1 or baseline level.
11. Negative pregnancy test for women of childbearing potential and agreement to use effective contraception.
12. Ability to understand and willingness to sign informed consent.

Exclusion Criteria:

1. HER2-positive gastric or gastroesophageal junction adenocarcinoma.
2. Squamous cell carcinoma, undifferentiated carcinoma, or mixed histology.
3. Active or uncontrolled central nervous system metastases.
4. Uncontrolled pleural effusion, ascites, or clinically significant pericardial effusion.
5. Weight loss greater than 20% within 2 months before enrollment.
6. Major surgery within 28 days before enrollment.
7. Prior anti-PD-1, anti-PD-L1, anti-CTLA-4, or other immune checkpoint inhibitor therapy.
8. Active autoimmune disease requiring systemic treatment.
9. Active hepatitis B, hepatitis C, or HIV infection.
10. Interstitial lung disease or uncontrolled systemic disease.
11. Significant cardiovascular disease within 6 months before enrollment.
12. Known hypersensitivity to study drugs or their components.
13. Participation in another interventional clinical trial within 4 weeks before enrollment.
14. History of substance abuse or severe psychiatric disorder.
15. History of rheumatic heart disease or known hypersensitivity to mannatide.
16. Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study evaluation.