{"entity":{"id":"fmt-checkpoint-nonresponders","kind":"technology","name":"Faecal microbiota transplantation for PD-1 non-responders","aka":[],"tldr":"Transplanting gut bacteria from patients who responded to immunotherapy into those who did not. In small studies a minority of resistant melanomas started responding. Randomised trials are running.","summary":"Two single-arm phase 1 studies published together in Science in 2021 (Pittsburgh, NCT03341143; Sheba, NCT03353402) gave responder-derived faecal microbiota transplantation (FMT) plus anti-PD-1 to patients with anti-PD-1-refractory melanoma: 6 of 15 and 3 of 10 patients had clinical benefit, with increased CD8 infiltration and engraftment of donor taxa. In the first-line setting, MIMic-01 (Montreal, NCT03772899, Nature Medicine 2023) combined healthy-donor FMT with anti-PD-1 in 20 patients and reported a 65% objective response rate, above historical controls. Randomised phase 2 trials are now running in Canada, Norway and the Netherlands using capsule FMT, and defined bacterial consortia and single-strain products (for example, CBM588, Akkermansia) are in development as a more controllable alternative. Donor screening, transmission risk and lack of a validated 'good microbiome' signature remain the problems.","status":"phase-2","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Fecal_microbiota_transplant","links":[{"label":"Davar et al. (Science 2021)","url":"https://doi.org/10.1126/science.abf3363"},{"label":"Routy et al. MIMic-01 (Nat Med 2023)","url":"https://doi.org/10.1038/s41591-023-02453-x"}],"tags":[],"related":["idea-microbiome-io-fmt","idea-bio2-fmt-plus-checkpoint-phase3"],"cancers":["melanoma","rcc","nsclc"],"sections":["nutrition-lifestyle","immunotherapy"],"technologies":["checkpoint-inhibitor","microbiome-modulation-io","dietary-fibre-microbiome-io"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity"],"trials":["fmt-pd1-refractory-melanoma-pitt","mimic-01"],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response"],"keyPapers":["paper-davar-science"],"journals":[],"dependsOn":[],"notes":[],"principle":"Replacing a non-permissive gut community with a responder-derived one restores microbial signals (metabolites, pattern-recognition ligands) that prime dendritic cells and systemic anti-tumour T-cell immunity.","strengths":["Responses in genuinely refractory patients","Agnostic to tumour genotype","Cheap relative to drugs"],"limitations":["Single-arm studies, small numbers","Donor variability and safety (screening for pathogens)","Antibiotics, diet and proton-pump inhibitors confound everything"]},"route":"/technologies/fmt-checkpoint-nonresponders/","neighbours":{"idea":[{"id":"idea-microbiome-io-fmt","kind":"idea","name":"Microbiome transplant as a routine immunotherapy adjunct","route":"/ideas/idea-microbiome-io-fmt/"},{"id":"idea-bio2-fmt-plus-checkpoint-phase3","kind":"idea","name":"Take faecal transplant plus immunotherapy to a definitive trial","route":"/ideas/idea-bio2-fmt-plus-checkpoint-phase3/"}],"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"section":[{"id":"nutrition-lifestyle","kind":"section","name":"Diet, Exercise & Lifestyle","route":"/fronts/nutrition-lifestyle/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"dietary-fibre-microbiome-io","kind":"technology","name":"Dietary fibre and the gut microbiome for immunotherapy response","route":"/technologies/dietary-fibre-microbiome-io/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"microbiome-modulation-io","kind":"technology","name":"Microbiome modulation to unlock immunotherapy","route":"/technologies/microbiome-modulation-io/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"pathway":[{"id":"microbiome-tumour","kind":"pathway","name":"Microbiome-tumour interactions","route":"/pathways/microbiome-tumour/"}],"term":[{"id":"gut-microbiome-diversity","kind":"term","name":"Gut microbiome diversity and composition","route":"/terms/gut-microbiome-diversity/"}],"trial":[{"id":"fmt-pd1-refractory-melanoma-pitt","kind":"trial","name":"FMT plus pembrolizumab in anti-PD-1-refractory melanoma (Pittsburgh)","route":"/trials/fmt-pd1-refractory-melanoma-pitt/"},{"id":"mimic-01","kind":"trial","name":"MIMic-01: healthy-donor FMT plus anti-PD-1, first-line melanoma","route":"/trials/mimic-01/"}],"person":[{"id":"laurence-zitvogel","kind":"person","name":"Laurence Zitvogel","route":"/people/laurence-zitvogel/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-davar-science","kind":"paper","name":"Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients","route":"/key-papers/paper-davar-science/"}],"roadmap":[{"id":"nutrition-lifestyle-roadmap","kind":"roadmap","name":"Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment","route":"/roadmaps/nutrition-lifestyle-roadmap/"}]}}