{"entity":{"id":"fmt-pd1-refractory-melanoma-pitt","kind":"trial","name":"FMT plus pembrolizumab in anti-PD-1-refractory melanoma (Pittsburgh)","aka":[],"tldr":"Fifteen melanoma patients whose immunotherapy had failed received a stool transplant from someone whose immunotherapy had worked, then restarted the drug. Six of them benefited, including three with lasting responses.","summary":"Single-arm study. Donors were seven melanoma patients with complete or durable partial responses to anti-PD-1. Of 15 recipients, 6 had clinical benefit (3 objective responses, 3 stable disease beyond 12 months); responders showed engraftment of donor taxa, increased CD8 T-cell activation and decreased IL-8-producing myeloid cells, and lower circulating IL-8. A companion Israeli study (Sheba, NCT03353402, 10 patients, 3 responders) was published alongside. Together they were the first human evidence that manipulating the microbiome can reverse checkpoint resistance, and they set off the current wave of randomised FMT and defined-consortium trials. Small, uncontrolled, and with a response rate a sceptic could attribute to re-challenge alone.","status":"completed","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov NCT03341143","url":"https://clinicaltrials.gov/study/NCT03341143"},{"label":"Davar et al. (Science 2021)","url":"https://doi.org/10.1126/science.abf3363"},{"label":"Baruch et al., Sheba (Science 2021)","url":"https://doi.org/10.1126/science.abb5920"}],"tags":[],"related":["idea-microbiome-io-fmt","idea-bio2-fmt-plus-checkpoint-phase3"],"cancers":["melanoma"],"sections":["nutrition-lifestyle","immunotherapy"],"technologies":["fmt-checkpoint-nonresponders","microbiome-modulation-io","checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity","orr"],"trials":[],"people":["jennifer-wargo"],"bottlenecks":["b-immunotherapy-response"],"keyPapers":["paper-davar-science","paper-baruch-science"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03341143","phase":"2","setting":"Metastatic melanoma with primary resistance to anti-PD-1: single colonoscopic FMT from a durable responder donor, then pembrolizumab","sponsor":"UPMC Hillman Cancer Center / NCI","result":"6 of 15 patients with clinical benefit (3 objective responses).","started":"2018-03-19","startedType":"actual","yearReported":2021,"enrolled":15,"enrolledBasis":"treated","enrolledNote":"ClinicalTrials.gov lists 20 participants (actual); the Science 2021 paper reports outcomes for the 15 patients who received FMT plus pembrolizumab.","outcomes":[{"endpoint":"Clinical benefit (objective response or SD over 12 months)","primary":true,"unit":"%","arms":[{"name":"FMT + pembrolizumab","n":15,"value":40}],"source":"https://doi.org/10.1126/science.abf3363"}],"replication":"Sheba study (Science 2021) concordant; randomised phase 2 trials (LND101 NCT06623461; Oslo NCT05286294) in progress."},"route":"/trials/fmt-pd1-refractory-melanoma-pitt/","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":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"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":"fmt-checkpoint-nonresponders","kind":"technology","name":"Faecal microbiota transplantation for PD-1 non-responders","route":"/technologies/fmt-checkpoint-nonresponders/"},{"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":"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/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"person":[{"id":"jennifer-wargo","kind":"person","name":"Jennifer A. Wargo","route":"/people/jennifer-wargo/"}],"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/"},{"id":"paper-baruch-science","kind":"paper","name":"Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients","route":"/key-papers/paper-baruch-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/"}]}}