Feasibility of antibiotic-assisted fecal microbiota transplantation with immunotherapy for esophageal and gastric cancer.

AIMS: Immune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens.

METHODS

This phase I - II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.