# Microbiome transplant as a routine immunotherapy adjunct

Source: https://onco.cc/ideas/idea-microbiome-io-fmt/  
OnCo record `idea-microbiome-io-fmt` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- 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.
- Proposed 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

## Sources

- Davar et al., Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma (Science 2021): https://doi.org/10.1126/science.abf3363
- Baruch et al., Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma (Science 2021): https://doi.org/10.1126/science.abb5920

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- institutions: [Gustave Roussy](https://onco.cc/institutions/gustave-roussy/), [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- pathways: [Microbiome-tumour interactions](https://onco.cc/pathways/microbiome-tumour/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Hallmark (2022): polymorphic microbiomes](https://onco.cc/terms/polymorphic-microbiomes/)
- trials: [CheckMate 227](https://onco.cc/trials/checkmate-227/), [CheckMate 915](https://onco.cc/trials/checkmate-915/), [Fianlimab + cemiplimab phase 3 (first-line melanoma)](https://onco.cc/trials/fianlimab-phase3-melanoma/), [FMT plus pembrolizumab in anti-PD-1-refractory melanoma (Pittsburgh)](https://onco.cc/trials/fmt-pd1-refractory-melanoma-pitt/), [KEYNOTE-042](https://onco.cc/trials/keynote-042/), [RELATIVITY-098](https://onco.cc/trials/relativity-098/)
- key papers: [CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition](https://onco.cc/key-papers/paper-pd-1-nsclc-am-j-clin-oncol-2016/), [Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients](https://onco.cc/key-papers/paper-davar-science/), [Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients](https://onco.cc/key-papers/paper-baruch-science/), [STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma](https://onco.cc/key-papers/paper-kras-nsclc-cancer-discov-2018/), [Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer](https://onco.cc/key-papers/paper-topalian-anti-pd1-nejm-2012/)
- technologies: [Faecal microbiota transplantation for PD-1 non-responders](https://onco.cc/technologies/fmt-checkpoint-nonresponders/)

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