Fecal microbiota capsule transplantation plus immunotherapy as first-line maintenance therapy for patients with malignant solid tumors: A single-arm, dose-escalation, exploratory phase I study

BACKGROUND: Chemotherapy combined with programmed cell death protein-1 (PD-1) antibody immunotherapy has become the standard first-line treatment for most patients with malignant solid tumors. However, data from multiple phase III trials indicate that even with first-line induction followed by immunotherapy maintenance, median progression-free survival (PFS) remains less than one year. METHODS: In this phase I dose-escalation trial (3 + 3 design), 12 patients who completed six cycles of first-line chemoimmunotherapy received oral fecal microbiota transplantation (FMT) capsules plus anti-PD-1 maintenance immunotherapy at escalating dose levels (i to i + 3). The primary endpoint was safety; secondary endpoints included the recommended phase II dose (RP2D), PFS, and disease control rate (DCR). Fecal and blood samples were collected for exploratory microbiome and metabolomic analyses. RESULTS: No grade ≥3 FMT-related toxicities occurred. With a median follow-up of 36.9 months, median PFS was 19.8 months (95% CI 11.2-28.4); maintenance-phase PFS was 11.7 months (95% CI 4.1-19.3). 4 patients remained progression-free on continued immunotherapy. Four patients (33.3%) experienced grade 1-2 gastrointestinal events. Microbiomic analyses showed post-FMT expansion of Blautia and Faecalibacterium, with dose level i + 1 demonstrating the greatest α-diversity shift and engraftment rate. Metabolomic analysis showed that serum arachidonic acid levels increased after FMT. CONCLUSION: Oral FMT combined with immunotherapy as first-line maintenance therapy for solid tumors was safe and well tolerated, showed promising preliminary efficacy, and induced favorable compositional changes in the gut microbiota. This study was registered with the Chinese Clinical Trial Registry (Registration No.: ChiCTR2100054928).