A safety trial of antibiotic fecal microbiota transplantation for esophageal and gastric cancer patients treated with immune checkpoint inhibitors (Biorich2 trial).

TPS510 Background: The development of immune checkpoint inhibitors (ICIs) has improved the prognosis of unresectable advanced or recurrent esophageal and gastric cancer. However, the prognosis remains poor. The human intestinal microbiota plays various roles in digestion, immunomodulation, and metabolism and is known to influence tumor suppression. Previous studies reported that intestinal microbiota can impact immune responses and the effectiveness of ICIs. Therefore, this study investigates the safety and efficacy of antibiotic fecal microbiota transplantation (A-FMT) in patients with unresectable advanced or recurrent esophageal or gastric cancer. Methods: Eligible patients are diagnosed with unresectable advanced or recurrent esophageal squamous cell carcinoma or gastric adenocarcinoma. The primary endpoint is to examine the dose-limiting toxicity (DLT) of A-FMT. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and biomarkers of efficacy and adverse events. This trial consists of two parts: safety confirmation, which assesses DLT incidence, and an expansion part, which examines efficacy and safety. The safety confirmation part will enroll 3-6 patients in cohort 1 (combination therapy with ICIs and chemotherapy) and cohort 2 (combination of anti-PD-1 and anti-CTLA4 antibodies). The expansion part will enroll untreated patients: 10 for esophageal cancer (ICIs + chemotherapy), 10 for anti-PD-1 + anti-CTLA4 antibodies, and 11 for gastric cancer (ICIs + chemotherapy). After enrollment, patients receive antibacterial agents for 1 week before FMT. Patients then undergo total colonoscopy after bowel cleaning with polyethylene glycol plus ascorbic acid. A 200 mL fecal suspension from a healthy donor is transferred to the patient's cecum, and ICIs with/without chemotherapy are initiated thereafter. Biomarker analysis explores diagnostic or surrogate biomarkers, aiming to identify molecular targets, cell populations, microbial species, and functions involved in efficacy by analyzing the effects of A-FMT and ICIs on the tumor microenvironment and intestinal microbiota using methods such as proteome analysis. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240170 and was initiated in August 2024, with enrollment ongoing. Clinical trial information: jRCTs031240170.