Mannatide Combined With CAPOX and Tislelizumab for Advanced Gastric Cancer.

A Multicenter, Single-Arm, Phase II Study of Mannatide Combined With CAPOX and Tislelizumab as First-Line Treatment for Recurrent or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Tislelizumab; Drug: Mannatide

Detailed Description

Gastric cancer remains one of the leading causes of cancer-related mortality worldwide. Although immune checkpoint inhibitors combined with chemotherapy have improved outcomes in advanced gastric and gastroesophageal junction adenocarcinoma, many patients still fail to achieve durable responses.

Mannatide is an immunomodulatory agent that has been shown to enhance both innate and adaptive immune responses. Preclinical and clinical studies suggest that mannatide may improve antitumor immunity through activation of macrophages, enhancement of antigen presentation, stimulation of T-cell proliferation, and promotion of natural killer cell activity. These properties provide a rationale for combining mannatide with chemotherapy and immune checkpoint blockade.

This study is a multicenter, open-label, single-arm phase II trial enrolling approximately 52 patients with unresectable recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma. Participants will receive CAPOX chemotherapy (oxaliplatin plus capecitabine), tislelizumab, and oral mannatide as first-line treatment.

Treatment will be administered for six induction cycles. Tumor assessments will be performed every two cycles according to RECIST version 1.1. Patients without disease progression may continue maintenance therapy consisting of capecitabine, tislelizumab, and mannatide until disease progression, unacceptable toxicity, withdrawal of consent, initiation of another anticancer therapy, death, or completion of the maximum treatment duration.

The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and safety. Exploratory endpoints include single-cell RNA sequencing, single-cell T-cell receptor sequencing, multiplex immunofluorescence analysis, and gut microbiome profiling to identify biomarkers associated with treatment response.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Liu, MD; Phone Number: +8618980606324; Email: liuming629@wchscu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
      • Contact: Ming Liu; Phone Number: +8618980606324; Email: liuming629@wchscu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAPOX + Tislelizumab + Mannatide; Participants will receive CAPOX chemotherapy (oxaliplatin and capecitabine), tislelizumab, and oral mannatide as first-line treatment for recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Drug: Oxaliplatin; Oxaliplatin 130 mg/m² administered intravenously on Day 1 of each 21-day treatment cycle as part of the CAPOX regimen.; Drug: Capecitabine; Capecitabine 1000 mg/m² orally twice daily on Days 1-14 of each 21-day treatment cycle.; Drug: Tislelizumab; Tislelizumab 200 mg administered intravenously on Day 1 of each 21-day treatment cycle.; Drug: Mannatide; Mannatide 10 mg administered orally three times daily throughout study treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST version 1.1.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Up to 24 months
Disease Control Rate (DCR)		Up to 24 months
Duration of Response (DoR)		Up to 24 months
Incidence of Adverse Events	Adverse events assessed according to NCI CTCAE version 5.0.	From first dose through 30 days after the last dose, up to 24 months.
Quality of Life (QoL)	Quality of life assessed using the EORTC QLQ-C30 questionnaire.	Baseline through completion of study treatment, up to 24 months.

Collaborators and Investigators

• Sponsor: Ming Liu

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: June 13, 2026
• First Submitted That Met QC Criteria: June 13, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 13, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gastric Cancer; Metastatic Gastric Cancer; Gastroesophageal Junction Cancer; Tislelizumab; CAPOX; First-Line Treatment; Mannatide; Phase II Study
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; tislelizumab; polyactin A
• Other Study ID Numbers: 2025 Review (2538)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No