Factors Influencing Immunotherapy Response in dMMR/MSI-H Gastric/Gastroesophageal Junction Adenocarcinoma

NCT ID: NCT07259473

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2029-12-30

Brief Summary

dMMR/MSI-H is a key molecular subtype of gastric cancer, found in 8-22% of cases. It is typically associated with older age, female sex, distal tumor location, and intestinal histology (Lauren classification). While this subtype predicts better survival in locally advanced disease, its prognostic role in metastatic settings is less clear.

Notably, dMMR/MSI-H tumors are often resistant to conventional chemotherapy. Conversely, they demonstrate exceptional sensitivity to immunotherapy. This has led to effective strategies using immune checkpoint inhibitors, either alone or combined with chemotherapy, in both neoadjuvant and advanced disease settings.

However, key challenges remain. Prospective data are largely from Western populations, leaving the efficacy in Asian patients-who bear a high disease burden-less defined. Furthermore, about half of dMMR/MSI-H patients exhibit primary or acquired resistance to immunotherapy. A deeper understanding of the tumor-immune dynamics during treatment is crucial to uncover resistance mechanisms and improve patient outcomes.

Conditions

Gastric / Gastroesophageal Junction Adenocarcinoma; Mismatch Repair Deficient or MSI-High Solid Tumors; Immunotherapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dMMR/MSI-H GC

Immunotherapy with induction chemotherapy

Group Type: EXPERIMENTAL

Immunotherapy

Intervention Type: DRUG

Drug: Immune checkpoint inhibitors (ICIs), specifically PD-1 antibodies, PD-L1 antibodies, PD-1/CTLA-4 bispecific antibodies, or PD-1/CTLA-4 combination therapy.

Regimen: 4 treatment cycles.

Induction chemotherapy

Intervention Type: DRUG

Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2

D2 radical gastrectomy

Intervention Type: PROCEDURE

Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.

Interventions

Immunotherapy

Drug: Immune checkpoint inhibitors (ICIs), specifically PD-1 antibodies, PD-L1 antibodies, PD-1/CTLA-4 bispecific antibodies, or PD-1/CTLA-4 combination therapy.

Regimen: 4 treatment cycles.

Intervention Type: DRUG

Induction chemotherapy

Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2

Intervention Type: DRUG

D2 radical gastrectomy

Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Male or female, aged 18 to 85 years.
• Histologically confirmed gastric cancer or adenocarcinoma of the esophagogastric junction (only Siewert types II and III are included).
• dMMR status confirmed by immunohistochemistry (IHC) or MSI-H status confirmed by PCR/NGS.
• Tumor clinical staging meeting the following criteria:

cT≥2, any N, M0, assessed by the investigator as potentially resectable and planned for preoperative treatment followed by surgery.

• Willing to receive treatment with immune checkpoint inhibitors (including, but not limited to, various PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors, PD-1/CTLA-4 bispecific antibodies, etc.), which may be combined with or without standard chemotherapy regimens for gastric cancer.

Exclusion Criteria

• Tumor histology other than adenocarcinoma, such as squamous cell carcinoma, neuroendocrine carcinoma, etc.
• Presence of central nervous system metastases and/or leptomeningeal carcinomatosis.
• Prior antitumor therapy directed at the current gastric cancer (excluding palliative gastrointestinal bypass surgery performed to relieve obstructive symptoms).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xuefei.Wang

Chief of Department of Gastrointestinal Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Zhaoqing Tang

Role: CONTACT

tang.zhaoqing@zs-hospital.sh.cn

021-64041990

Other Identifiers

B2025-541R

Identifier Type: -

Identifier Source: org_study_id