# Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial

Source: https://onco.cc/key-papers/paper-mimic-01-nat-med-2023/  
OnCo record `paper-mimic-01-nat-med-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the trial registered as NCT03772899, in Nature Medicine (2023), chosen as the most cited paper whose own text cites the registry id.

## Summary

Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier NCT03772899.

Indexed on Europe PMC as PubMed record 37414899 (DOI 10.1038/s41591-023-02453-x). Its abstract cites the registry id NCT03772899, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature Medicine
- Year: 2023
- DOI: 10.1038/s41591-023-02453-x
- Authors: Routy B, Lenehan JG, Miller WH, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT03772899 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- Nat Med 2023: https://doi.org/10.1038/s41591-023-02453-x
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37414899/
- Europe PMC: https://europepmc.org/article/MED/37414899
- ClinicalTrials.gov NCT03772899: https://clinicaltrials.gov/study/NCT03772899

## Connected records

- trials: [MIMic-01: healthy-donor FMT plus anti-PD-1, first-line melanoma](https://onco.cc/trials/mimic-01/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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