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

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.

NCT Number	NCT07259473
Lead Sponsor	Shanghai Zhongshan Hospital
Conditions	Gastric / Gastroesophageal Junction Adenocarcinoma, Mismatch Repair Deficient or MSI-High Solid Tumors, Immunotherapy
Enrollment	15 participants
Start Date	2026-01-31
Primary Completion	2029-12-30 (estimated)
Study Completion	2029-12-30 (estimated)
Updated on ClinicalTrials.gov	2026-01-07