{"entity":{"id":"idea-microbiome-io-fmt","kind":"idea","name":"Microbiome transplant as a routine immunotherapy adjunct","aka":[],"tldr":"Stool transplants from immunotherapy responders have rescued some non-responders in melanoma. If defined bacterial cocktails work as well, every immunotherapy patient could get one.","summary":"This idea proposes microbiome transplant as a routine immunotherapy adjunct: stool from responders has rescued some non-responders in Melanoma, and defined bacterial cocktails could reach every immunotherapy patient. Phase 1/2 FMT studies (Davar, Baruch) converted a fraction of refractory melanoma patients, defined consortia (SER-155, VE800) and diet trials are ongoing, and durability is unclear. The hypothesis is that a defined consortium with first-line PD-1 blockade raises the response rate in melanoma and Non-small-cell lung cancer, supported by causal FMT data and the harm done by antibiotics. The test is a placebo-controlled phase 2/3, and the idea sits within the Microbiome-tumour interactions pathway and the hallmark Polymorphic microbiomes.","asOf":"2026-09-08","links":[{"label":"Davar et al., Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma (Science 2021)","url":"https://doi.org/10.1126/science.abf3363"},{"label":"Baruch et al., Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma (Science 2021)","url":"https://doi.org/10.1126/science.abb5920"}],"tags":["mechanism","open-question"],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":[],"targets":["pd1"],"drugs":[],"companies":[],"institutions":["md-anderson","gustave-roussy"],"pathways":["microbiome-tumour","pd1-checkpoint"],"terms":["polymorphic-microbiomes"],"trials":["checkmate-227","checkmate-915","fianlimab-phase3-melanoma","keynote-042","relativity-098"],"people":[],"bottlenecks":[],"keyPapers":["paper-davar-science","paper-baruch-science","paper-topalian-anti-pd1-nejm-2012","paper-pd-1-nsclc-am-j-clin-oncol-2016","paper-kras-nsclc-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A defined bacterial consortium given with first-line PD-1 blockade increases response rate in melanoma and NSCLC compared with placebo, with effect size dependent on baseline microbiome composition.","rationale":"Consistent associations across cohorts, causal FMT data, and the fact that antibiotics worsen outcomes.","test":"Placebo-controlled phase 2/3 of a consortium plus PD-1 in first-line melanoma with stratification by baseline microbiome, endpoints ORR and PFS.","maturity":"early-clinical"},"route":"/ideas/idea-microbiome-io-fmt/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"institution":[{"id":"gustave-roussy","kind":"institution","name":"Gustave Roussy","route":"/institutions/gustave-roussy/"},{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"pathway":[{"id":"microbiome-tumour","kind":"pathway","name":"Microbiome-tumour interactions","route":"/pathways/microbiome-tumour/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"polymorphic-microbiomes","kind":"term","name":"Hallmark (2022): polymorphic microbiomes","route":"/terms/polymorphic-microbiomes/"}],"trial":[{"id":"checkmate-227","kind":"trial","name":"CheckMate 227","route":"/trials/checkmate-227/"},{"id":"checkmate-915","kind":"trial","name":"CheckMate 915","route":"/trials/checkmate-915/"},{"id":"fianlimab-phase3-melanoma","kind":"trial","name":"Fianlimab + cemiplimab phase 3 (first-line melanoma)","route":"/trials/fianlimab-phase3-melanoma/"},{"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":"keynote-042","kind":"trial","name":"KEYNOTE-042","route":"/trials/keynote-042/"},{"id":"relativity-098","kind":"trial","name":"RELATIVITY-098","route":"/trials/relativity-098/"}],"paper":[{"id":"paper-pd-1-nsclc-am-j-clin-oncol-2016","kind":"paper","name":"CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition","route":"/key-papers/paper-pd-1-nsclc-am-j-clin-oncol-2016/"},{"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/"},{"id":"paper-kras-nsclc-cancer-discov-2018","kind":"paper","name":"STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma","route":"/key-papers/paper-kras-nsclc-cancer-discov-2018/"},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","route":"/key-papers/paper-topalian-anti-pd1-nejm-2012/"}],"technology":[{"id":"fmt-checkpoint-nonresponders","kind":"technology","name":"Faecal microbiota transplantation for PD-1 non-responders","route":"/technologies/fmt-checkpoint-nonresponders/"}]}}