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Factors Influencing Immunotherapy Response in dMMR/MSI-H Gastric/Gastroesophageal Junction Adenocarcinoma
Sponsor: Shanghai Zhongshan Hospital
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.
Official title: Factors Influencing Immunotherapy Response in Mismatch Repair Deficiency (dMMR) / Microsatellite Instability-High (MSI-H) Gastric/Gastroesophageal Junction Adenocarcinoma
Key Details
Gender
All
Age Range
18 Years - 85 Years
Study Type
INTERVENTIONAL
Enrollment
15
Start Date
2026-01-31
Completion Date
2029-12-30
Last Updated
2026-01-07
Healthy Volunteers
No
Conditions
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.
Induction chemotherapy
Drug: Oxaliplatin Regimen: 1 cycle Dosage: 130mg/m\^2
D2 radical gastrectomy
Curative-intent D2 radical gastrectomy is scheduled 4-6 weeks after completion of the fourth cycle.