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1 februari 2026: Bron: Nature medicine Published: Canbiome2 bij patiënten met gevorderde melanoom moet de verbeterde effectiviteit van een FTM = Fecale Microbiota transplantatie  / poeptransplantatie gecombineerd met immuuntherapie aan gaan tonen.

Hier achtereenvolgens de abstracten van de genoemde studies hierboven:

Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial

Nature Medicine (2026)Cite this article

Abstract

Immune checkpoint inhibitors (ICI) have improved outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma, yet over half of patients exhibit primary resistance. Fecal microbiota transplantation (FMT) may overcome resistance to anti-programmed cell death protein 1 (PD-1) therapy. The clinical activity and safety of FMT plus anti-PD-1 in NSCLC or anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy in melanoma have not been evaluated. Here we report results from FMT-LUMINate, a multicenter, open-label, phase 2 trial assessing healthy donor FMT plus anti-PD-1 in NSCLC (n = 20) or anti-PD-1 plus anti-CTLA-4 (dual ICI) in melanoma (n = 20), in the first-line setting. Eligible patients received a single FMT via oral capsules prior to ICI initiation. The primary endpoint was objective response rate (ORR) in NSCLC. Secondary endpoints included ORR in melanoma, safety and donor−host microbiome similarity. In NSCLC, the ORR was 80% (16/20), meeting the study primary endpoint. In melanoma, the ORR was 75% (15/20). FMT was deemed safe in both cohorts by an independent data and safety monitoring committee, with no grade 3 or higher adverse events (AEs) in NSCLC and 13 (65%) patients experiencing grade 3 or higher AEs in melanoma. Shotgun metagenomic sequencing revealed that responders developed a distinct post-FMT gut microbiome composition, independent of acquired donor−recipient similarity or strain-level engraftment. Responders exhibited significantly greater loss of baseline bacterial species compared to non-responders, with frequent depletion of Enterocloster citroniae, E. lavalensis and Clostridium innocuum. This finding was reproduced across three published FMT oncology trials. We recolonized antibiotic-treated, tumor-bearing mice with post-FMT stool from two responder patients, and reintroduction of the specific bacterial species that were lost after FMT abrogated the antitumor effect of ICI. Taken together, these findings confirm the clinical activity of FMT in combination with ICI and suggest that the elimination of deleterious taxa is required for FMT-mediated therapeutic benefit. ClinicalTrials.gov identifier: NCT04951583.






Improved survival in advanced melanoma patients treated with fecal microbiota transplantation using healthy donor stool in combination with anti-PD1

Improved survival in advanced melanoma patients treated with fecal microbiota transplantation using healthy donor stool in combination with anti-PD1:

Abstract

BackgroundMicrobiome manipulation research is focused on developing techniques to modify the gut microbiome and augment responses to immune checkpoint inhibitors (ICI). Fecal microbiota transplantation (FMT) represents a potential strategy to overcome primary or acquired resistance to ICI. 20 patients with advanced melanoma were enrolled in a phase I multicenter trial to evaluate the safety and response to anti-PD1 combined with FMT using healthy donor stool as first-line treatment (MIMic, NCT03772899). Combination therapy was safe, and the objective response rate (ORR) was 65%. We now report survival data based on over 3 years of follow-up. Patients with advanced melanoma and treatment-naïve for advanced disease received a single FMT with healthy donor stool followed by standard anti-PD1 therapy. Progression-free survival (PFS) and overall survival (OS) were measured from the date of FMT to event. Radiographic response was measured using RECIST 1.1 criteria. Both median PFS (mPFS) and median OS (mOS) were determined using the Kaplan-Meier method. Post hoc analyses assessed the impact of specific factors on survival outcomes. Minimum follow-up was 40 months from the date of FMT of the last patient, with the longest surviving patient in complete response at 62.2 months. At the time of data analysis, eight patients were alive and seven patients were without progression. No patients remain on anti-PD1 therapy. Only two patients received additional lines of therapy. The mPFS was 29.6 months and mOS 52.8 months. The 1, 2, and 3 years estimated survival rates were 95%, 74% and 53%, respectively. Post hoc analysis demonstrated significantly improved mPFS in responders and patients with FMT-specific toxicity. Combining first-line anti-PD1 therapy and oral FMT with healthy donor stool in this small cohort was safe and demonstrated an improvement in ORR, mPFS, and mOS, compared with randomized trials. Our sample size was small, and results were only hypothesis generating. The potential benefit of microbiome manipulation using oral FMT from healthy donors prior to ICI in patients with advanced melanoma will be evaluated in the ME.17 randomized phase 2 Canadian study (NCT06623461).

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Data availability

Raw FASTQ files are publicly available on the National Center for Biotechnology Information biorepository with accession number PRJNA1289847. Study-level clinical data from this study (including the protocol) will be made available upon reasonable request from a qualified medical or research professional for the specific purpose laid out in that request and may include deidentified individual participant data. A response to this data request will be made within approximately 14 days. The data for this request will be available after a data transfer agreement has been signed. Requests should be sent to the corresponding author. Patient-related data not included in the paper were generated as part of a clinical trial and are subject to patient confidentiality.

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Acknowledgements

The authors thank the patients, their families and their caregivers. This study was funded by the Canadian Cancer Society Impact Grant. The study was also partially funded by the Weston Family Foundation (Weston Family Foundation Proof-of-Concept Grant). We thank the Unité d’Innovations Thérapeutiques at the CRCHUM. We thank the staff at the CRCHUM animal facility and the immunomonitoring facility. We thank the staff at Génome Québec. A.E. was supported by the Seerave Foundation, the Fonds de recherche Québec–Santé (FRQS) Clinician Scientist Award, the Canadian Cancer Society, the Cancer Research Society Next Generation of Scientists and the Society of Immunotherapy of Cancer−Melanoma Research Alliance Women in Melanoma Award. For the present work, A.E. was also partially supported by the Guy Lafleur Foundation, the Institut de Cancer de Montréal and the ASCO Conquer Cancer Foundation Young Investigator Award. B.R. is supported by the Seerave Foundation, the Canadian Cancer Society and the FRQS Clinician Scientist Award. S.M.V. received salary support from the Ontario Institute of Cancer Research and the London Health Sciences Foundation Helen and Andy Spriet funds. M.S. received grant support for this work from the St. Joseph’s Health Care Foundation. L.D. is supported by the 2025 AACR Career Development Award in Lung Cancer Research and by the Association Robert Debré pour la Recherche Médicale. L.Z. is funded by the European Research Council (ERC) under grant agreement no. 101052444. L.Z. and L.D. are supported by the Seerave Foundation, the European Union’s Horizon Europe research and innovation program under grant agreement no. 101095604 (project acronym: PREVALUNG-EU, project title: Personalized lung cancer risk assessment leading to stratified interception), the European Union’s Horizon 2020 research and innovation program under grant agreement no. 825410 (ONCOBIOME project), the European Union’s Horizon 2020 research and innovation program under grant agreement no. 964590 (project acronym: IHMCSA, project title: International Human Microbiome Coordination and Support Action. ANR Ileobiome - 19-CE15-0029-01, ANR RHU5 ‘ANR-21-5 RHUS-0017’ IMMUNOLIFE, MAdCAM INCA_ 16698 and Ligue contre le cancer). L.D. was also funded by the SIGN’IT ARC Foundation (MICROBIONT-PREDICT (2021)). G.K. is supported by the Ligue contre le Cancer (équipes labellisées); Agence Nationale de la Recherche (ANR) under the France 2030 program (reference no. 21-ESRE-0028, ESR/Equipex+ Onco-Pheno-Screen; program RHU ANR-21-RHUS-0017 IMMUNOLIFE and ANR-23-RHUS-0010 LUCA-pi; ANR-22-CE14-0066 VIVORUSH, ANR-23-CE44-0030 COPPERMAC, ANR-23-R4HC-0006 Ener-LIGHT), an ERC Advanced Investigator Award (ERC-2021-ADG, grant no. 101052444; project acronym: ICD-Cancer); the Hevolution Network on Senescence in Aging (reference HF-E Einstein Network); European Union Horizon 2020 research and innovation programs Oncobiome (grant agreement no. 825410) and Prevalung (grant agreement no. 101095604), Institut National du Cancer (INCa), Institut Universitaire de France; PAIR-Obésité INCa_18713, Seerave Foundation, SIRIC Cancer Research and Personalized Medicine (CARPEM, SIRIC CARPEM INCa-DGOS-Inserm-ITMO Cancer_18006 supported by Institut National du Cancer, Ministère des Solidarités et de la Santé and INSERM). This study (Immuno-Onco) contributes to the IdEx Université de Paris Cité ANR-18-IDEX-0001.

Author information

Author notes

  1. These authors contributed equally: Sreya Duttagupta, Meriem Messaoudene.

  2. These authors jointly supervised this work: Bertrand Routy, Arielle Elkrief.

Authors and Affiliations

  1. Axe Cancer, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada

    Sreya Duttagupta, Meriem Messaoudene, Sebastian Hunter, Antoine Desilets, Rahima Jamal, Wiam Belkaid, Mayra Ponce, Mallia Geiger, Julie Malo, Alysé Filin, Diana Rusu, Babacar Mbaye, Imen Ben Aissa, Normand Blais, Mustapha Tehfe, Karl Bélanger, Jade Maillou, Somayeh Nili, Diogjena Katerina Prifti, Bertrand Routy & Arielle Elkrief

  2. Department of Microbiology & Immunology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada

    Sreya Duttagupta & Jade Maillou

  3. Hemato-Oncology Division, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada

    Antoine Desilets, Rahima Jamal, Normand Blais, Mustapha Tehfe, Karl Bélanger, Bertrand Routy & Arielle Elkrief

  4. Departments of Oncology and Medicine, McGill University, Montreal, Québec, Canada

    Catalin Mihalcioiu, Scott Owen, Benjamin Shieh & Nicholas Rozza

  5. Hemato-Oncology Division, Centre hospitalier de l’Université de Québec, Québec City, Québec, Canada

    Nicolas Marcoux

  6. Université Paris-Saclay, U1015 INSERM, Gustave Roussy, Ligue Labellisée contre le Cancer, Villejuif, France

    Marine Fidelle, Deborah Suissa, Lisa Derosa & Laurence Zitvogel

  7. Department of Computational, Cellular and Integrative Biology, University of Trento, Trento, Italy

    Gianmarco Piccinno, Michal Punčochář, Vitor Heidrich, Federica Pinto, Federica Armanini & Nicola Segata

  8. Centre de Recherche des Cordeliers, Équipe labellisée par la Ligue contre le cancer, Institut Universitaire de France, Paris, France

    Sylvere Durand & Guido Kroemer

  9. Université Paris-Saclay, INSERM US23 / CNRS UAR 3655, Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France

    Sylvere Durand & Guido Kroemer

  10. GMT Science, Rouen, France

    Vadim Puller & Raynald de Lahondès

  11. Department of Medicine, Division of Infectious Diseases, Western University, London, Ontario, Canada

    Seema Nair Parvathy & Michael Silverman

  12. Division of Infectious Diseases, St. Joseph’s Health Care, London, Ontario, Canada

    Seema Nair Parvathy & Michael Silverman

  13. Lawson Research Institute, London, Ontario, Canada

    Seema Nair Parvathy & Michael Silverman

  14. Verspeeten Family Cancer Centre at London Health Sciences Centre, London, Ontario, Canada

    Jacques Raphael, John Lenehan, Daniel Breadner & Saman Maleki Vareki

  15. Department of Oncology, Division of Medical Oncology, Schulich School of Medicine and Dentistry at Western University, London, Ontario, Canada

    Jacques Raphael, John Lenehan & Daniel Breadner

  16. R.S. McLaughlin Durham Regional Cancer Center at Lakeridge Health, Oshawa, Ontario, Canada

    Jeffrey Rothenstein

  17. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Seunghee Kim-Schulze & Thomas U. Marron

  18. Université Paris Cité, Sorbonne Université, Inserm, Centre de Recherche des Cordeliers, Paris, France

    Guido Kroemer

  19. Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France

    Guido Kroemer

  20. Gustave Roussy Cancer Campus (GRCC), ClinicObiome, Villejuif, France

    Lisa Derosa & Laurence Zitvogel

  21. Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

    Saman Maleki Vareki

  22. Division of Experimental Oncology, Department of Oncology, Western University, London, Ontario, Canada

    Saman Maleki Vareki

  23. Ontario Institute of Cancer Research, Toronto, Ontario, Canada

    Saman Maleki Vareki

Contributions

Conceptualization: A.E., B.R. and S.M.V. Methodology: all authors. Investigation: all authors. Formal analysis: S.D., S.H., M.M., M.F., A.D., I.B., D.S., D.R., M.G., G.P., M.P., A.F., V.H., R.L. and V.P. Data curation: A.D., I.B., W.B., N.B., M.T., S.O., K.B., B.S., J.R., J.L., D.B., N.M., D.K.P., N.R., S.N., F.P. and F.A. Resources: all authors. Writing—original draft: A.E., B.R. and S.D. Writing—review and editing: all authors. Visualization: all authors. Supervision: A.E. and B.R. Project administration: A.E., B.R. and S.M.V. Funding acquisition: A.E., B.R. and S.M.V.

Corresponding author

Correspondence to Arielle Elkrief.

Ethics declarations

Competing interests

A.D. received research funding from AstraZeneca, Exelixis, Regeneron and Fondation Saputo; advisory board and consulting fees from Boehringer Ingelheim, EMD Serono, Merck and Johnson & Johnson/Janssen; and speaker honoraria from Boehringer Ingelheim and AstraZeneca. A.E. declares grant support from Kanvas Biosciences, GMT Science, AstraZeneca, Merck and Bristol Myers Squibb. A.E. declares honoraria from AstraZeneca, Merck, Bristol Myers Squibb and EMD Soreno. A.E. declares consulting fees from EverImmune, NECBio and Sanofi-Pasteur. A.E. is inventor on patent 4872-8531-1934.1 regarding the microbiome and immunotherapy response. B.R. declares research funding from Davolterra and Kanvas Biosciences and consulting fees from Merck, AstraZeneca, EverImmune and Bristol Myers Squibb. B.R. is also a co-founder of Curebiota. S.M.V. reports a grant from Microviable Therapeutics outside the submitted work as well as consulting fees from Kanvas Biosciences and FedBio. S.M.V. is a co-founder of LND Therapeutics, Inc., which holds the rights to LND101. S.M.V. reports US Patent Application No. 63/913,940 related to FMT donor screening. M.S. is a co-founder of LND Therapeutics, Inc., which holds the rights to LND101. M.S. reports US Patent Application No. 63/913,940 related to FMT donor screening. S.P. is a co-founder of LND Therapeutics, Inc., which holds the rights to LND101. G.K. has been holding research contracts with Daiichi-Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys and Vascage. G.K. is on the Board of Directors of Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of EverImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. G.K. is on the scientific advisory boards of Hevolution, Institut Servier and Rejuveron Life Sciences/Centenara Labs AG. G.K. is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. Among these patents, one, ‘Methods for weight reduction’ (US11905330B1), is relevant to this study. A close family member of G.K. was an employee of Sanofi and now consults for Boehringer Ingelheim. J.R. reports participating in advisory boards for Merck, AstraZeneca, Lilly and Novartis. S.O. reports honoraria/consulting fees from AstraZeneca, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, Merck, Pfizer and Roche. The other authors declare no competing interests.

Peer review

Peer review information

Nature Medicine thanks Diwakar Davar, Jun Zhang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Saheli Sadanand, in collaboration with the Nature Medicine team.

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melanomen, niet-kleincellige longkanker, immuuntherapie, Poeptransplantatie, Fecale Microbiota Transplantatie, FMT, FMT-LUMINate fase 2 studie


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