Oxaliplatin: Oxaliplatin 130 mg/m² administered intravenously on Day 1 of each 21-day treatment cycle as part of the CAPOX regimen.
Capecitabine: Capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 21-day treatment cycle.
Tislelizumab: Tislelizumab 200 mg administered intravenously on Day 1 of each 21-day treatment cycle.
Mannatide: Mannatide 10 mg administered orally three times daily throughout study treatment.
Study summary
This is a multicenter, open-label, single-arm phase II study evaluating the efficacy and safety of mannatide in combination with CAPOX chemotherapy and tislelizumab as first-line treatment for patients with recurrent or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
Eligible patients will receive oxaliplatin, capecitabine, tislelizumab, and oral mannatide. Tumor response will be assessed according to RECIST version 1.1. Patients without disease progression after induction treatment may continue maintenance therapy with capecitabine, tislelizumab, and mannatide.
The primary objective is to evaluate objective response rate (ORR). Secondary objectives include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and safety. Exploratory analyses will investigate immune microenvironment changes and potential predictive biomarkers using blood, tumor tissue, and stool samples.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Objective Response Rate (ORR) — From treatment initiation until disease progression, assessed every 6 weeks during induction treatment and every 6 to 8 weeks during maintenance treatment, up to 24 months. Objective response rate defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST version 1.1.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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