{"entity":{"id":"idea-bio2-fmt-plus-checkpoint-phase3","kind":"idea","name":"Take faecal transplant plus immunotherapy to a definitive trial","aka":[],"tldr":"Transferring gut bacteria from patients who responded to immunotherapy has helped some patients who had stopped responding. It is time for a proper large trial.","summary":"Two independent phase 1 studies reported that faecal microbiota transplant from checkpoint responders re-sensitised some anti-PD-1-refractory melanoma patients, and a first-line study of donor transplant with checkpoint blockade showed feasibility and encouraging response. The field has stayed in small single-arm studies for years. A randomised trial with a defined donor consortium, standardised product and pre-specified microbiome endpoints would settle whether the effect is real.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","rcc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":["gustave-roussy","princess-margaret"],"pathways":[],"terms":[],"trials":[],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Faecal microbiota transplant from selected responder donors plus anti-PD-1 improves response rate compared with anti-PD-1 alone in checkpoint-refractory melanoma, with engraftment of donor taxa as a mechanistic mediator.","rationale":"The mouse causal data are strong, human phase 1 signals are reproducible across two centres, and the intervention is inexpensive. The main risks are donor variability and product standardisation, both addressable through consortium banking.","test":"A randomised phase 2 with pooled standardised donor product, primary endpoint objective response, and mandatory metagenomic sequencing to link engraftment with response.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-fmt-plus-checkpoint-phase3/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"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/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"institution":[{"id":"gustave-roussy","kind":"institution","name":"Gustave Roussy","route":"/institutions/gustave-roussy/"},{"id":"princess-margaret","kind":"institution","name":"Princess Margaret Cancer Centre","route":"/institutions/princess-margaret/"}],"person":[{"id":"laurence-zitvogel","kind":"person","name":"Laurence Zitvogel","route":"/people/laurence-zitvogel/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}],"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/"}]}}