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1 februari 2026: Bron: Nature Published: 28 January 2026

Wanneer patiënten met onbehandelde gevorderde niercelkanker vooraf en tijdens de behandeling met immuuntherapie een FTM = Fecale Microbiota transplantatie ook wel poeptransplantatie genoemd krijgen toegediend dan verbetert de effectiviteit van de immuuntherapeutische behandeling plus dat er geen ernstige bijwerkingen hoger dan graad 3 optraden. Dat blijkt uit de fase I veiligheidsstudie PERFORM.

Tijdens de studie kregen alle 15 patiënten drie keer een poeptransplantatie toegediend. Vijf patiënten hebben niet alle drie de geplande FMT-doseringen voltooid: drie patiënten haakten af vanwege immuungerelateerde colitis, één patiënt omdat de FMT-donor positief testte op Shiga-toxineproducerende Escherichia coli en één patiënt vanwege immuungerelateerde artritis. Geen van deze incidenten werd toegeschreven aan FMT-gerelateerde toxiciteit. Met uitzondering van de bevinding met Shiga-toxine werd de toediening uit voorzorg uitgesteld vanwege toxiciteit gerelateerd aan de gebruikte anti-PD medicijnen - immuuncheckpointremmers en niet vanwege FMT.

Hoewel dit een kleinschalige studie betreft met 20 deelnemende patiënten zijn de resultaten veelbelovend. Uit het studierapport vertaalt:

Van de 18 evalueerbare patiënten bereikten negen patiënten (50%) een objectieve respons, waaronder twee complete responsen (CR's) (11%), en zes (33%) hadden een stop op primaire progressieve ziekte (PD) als beste respons.
Twaalf patiënten (67%) behaalden klinisch voordeel, gedefinieerd als CR - complete remissie, partiële respons (PR) of stabiele ziekte (SD) gedurende ≥6 maanden (Fig. 1c−e).
Om de invloed van de donor op de werkzaamheid te beoordelen, hebben we de patiënten ingedeeld op basis van de donor en hun beste algehele gemiddelde respons (Fig. 1e and Extended Data Fig. 1b).
Klinische respons werd waargenomen bij ontvangers van fecale microbiële transplantatie (FMT) van vijf van de zeven donoren (Fig. 1e and Extended Data Fig. 1b).
Van de twee patiënten met niet-meetbare ziekte staakte patiënt 3 de behandeling met ipilimumab/nivolumab na 8 maanden vanwege toxiciteit en is na 54 maanden nog steeds ziektevrij.
Patiënt 15 heeft de behandeling met pembrolizumab afgerond en zet de behandeling met axitinib voort zonder dat de ziekte na 32 maanden is voortgeschreden.

Zie ook deze grafische afbeelding van de resultaten van de studie:

a, Stroomdiagram met het aantal gescreende, ingeschreven en met de studiemedicatie ontvangen patiënten. b, Studieopzet en tijdlijn van monstername en toediening van de behandeling. c, Spinnenwebdiagram dat de respons weergeeft als de verandering in grootte van de doellocaties ten opzichte van de baseline. Radiografische responsen werden bepaald volgens RECIST v1.1. Patiënten met een complete respons (CR) worden weergegeven in donkerblauw; patiënten met een partiële respons (PR) in lichtblauw; patiënten met stabiele ziekte (SD) ≥6 maanden in geel; en patiënten met progressieve ziekte (PD) of SD <6 maanden in rood. d, Zwemmerdiagram dat de behandelingsduur weergeeft voor patiënten met meetbare ziekte (n = 18) met een beste respons van CR, PR, SD en PD. Zowel de tijd tot de eerste respons als de status op het moment van de data-afsluiting worden weergegeven. e, Watervaldiagram dat de beste respons weergeeft van patiënten met meetbare ziekte (n = 18) in vergelijking met hun gezonde donor. f, Staafdiagrammen die het percentage niet-responders (NR, n = 9) en responders (R, n = 9; patiënten die CR of PR bereikten volgens RECIST v1.1) weergeven, evenals NR-patiënten met en zonder toxiciteit van graad 3 of hoger. Een tweezijdige χ²-test met Yates-correctie bevestigt een significant verband tussen respons en toxiciteit. PEG, polyethyleenglycol.

Omdat het eerste doel van de studie was om het effect van een poeptransplantatie te meten op de bijwerkingen constateerden de onderzoekers dit:

Slechts één van de negen patiënten die goed op de poeptransplantatie reageerden (11%) ondervond ernstige bijwerkingen van graad 3. Daarentegen ontwikkelden acht van de negen patiënten die niet reageerden op de poeptransplantatie (89%) ernstige bijwerkingen van graad 3, waaronder zes met graad 3 colitis. Een tweezijdige χ²-test met Yates-correctie bevestigde een significant verband tussen respons en toxiciteit (χ² = 8,00, P = 0,005), waarbij responders minder graad 3 irAE's vertoonden (Fig. 1f). Na een mediane follow-up van 21,9 maanden was de mediane progressievrije overleving (PFS) 11,15 maanden in de per-protocolpopulatie (n = 18) en de mediane algehele overleving 36 maanden in de intentie tot genezing - ITT-populatie (n = 20) (Extended Data Fig. 1d,e).

Al met al is dus een FTM = Fecale Microbiota transplantatie / poeptransplantatie een hoopvolle toevoeging voor kankerpatiënten met niercelkanker die in aanmerking komen voor immuuntherapie.

Het volledige studierapport is gratis in te zien. Klik daarvoor op de titel van het abstract:

Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial

Ricardo Fernandes,
Behnam Jabbarizadeh,
Adnan Rajeh,
Megan M Y Hong,
Kelly J. Baines,
Scott Ernst,
Eric Winquist,
Anorin Shadi Ali,
Susanne Penny,
Rene Figueredo,
Seema Nair Parvathy,
John G. Lenehan,
Devanand M. Pinto,
Michael S. Silverman &
Saman Maleki Vareki Nature Medicine (2026)Cite this article

Abstract

Immune checkpoint inhibitors (ICIs) improve outcomes in metastatic renal cell carcinoma (mRCC) but are hindered by immune-related adverse events (irAEs). Modulation of the gut microbiome may enhance efficacy and mitigate toxicity, yet the safety and mechanisms of healthy donor fecal microbiota transplantation (FMT) in mRCC remain unexplored. In this phase 1 trial, 20 treatment-naive patients with mRCC received encapsulated healthy donor FMT (LND101) combined with ipilimumab/nivolumab (n = 16), pembrolizumab/axitinib (n = 3) or pembrolizumab/lenvatinib (n = 1). The primary endpoint was safety, defined by the incidence and severity of irAEs. Secondary endpoints included clinical response (Response Evaluation Criteria in Solid Tumors version 1.1), gut microbiome and immune correlates and patient-reported quality of life. The safety endpoint was met with 50% (10/20) of patients experiencing grade 3 irAEs and no serious FMT-related toxicities or grade 4 or 5 irAEs. Among evaluable patients, the objective response rate was 50% (9/18), including two complete responses (11%, 2/18). Notably, most treatment responders did not develop any grade 3 or higher irAEs. Alpha (α) diversity improvement and durable engraftment of taxa and metabolic functions associated with anti-inflammatory properties correlated with reduced toxicity and improved response. Conversely, patients experiencing grade 3 irAEs exhibited expansion of Segatella copri, particularly with ipilimumab/nivolumab, and elevated levels of donor-derived microbial enzymes previously linked to pro-inflammatory activity. Resilience to toxicity correlated with the maintenance of protective metabolites and increased levels of immune regulatory cells, whereas the presence of grade 3 irAEs and S. copri enrichment was associated with high immune dysregulation. These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated mRCC. ClinicalTrials.gov identifier: NCT04163289.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

Data availability

All clinical metadata have been uploaded to the National Center for Biotechnology Information Sequence Read Archive, BioProject ID PRJNA1290813. Patient baseline clinical data are available in Tables 1 and 2 and within the text. Qualified medical or scientific professionals may request access to study-level clinical data (including the protocol) for a defined research purpose, and deidentified individual participant data may be provided. Initial requests will be responded to within approximately 14 days, and data will be made available within 30 days after a data sharing 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

We thank the patients and their families. We thank the Clinical Research Unit at the Verspeeten Family Cancer Centre for trial management. We acknowledge the staff at the London Regional Flow Cytometry Facility at Robarts Research Institute for their help with the flow experiments. The clinical trial was primarily funded by philanthropic donations to S.M.V. and R.F. through the London Health Sciences Foundation clinical trials program. A grant from the Academic Medical Organization of Southwestern Ontario was awarded to R.F. and S.M.V. A grant from the Division of Medical Oncology at Western University was awarded to R.F. and S.M.V. A grant from the Verspeeten Family Cancer Centre Catalyst grant program was awarded to R.F. and S.M.V. The S.M.V. laboratory for ancillary analyses and biobanking was funded by grants awarded to S.M.V. from the Lotte and John Hecht Memorial Foundation (1-MR_2022_4884), the Weston Family Foundation and a project grant from the Canadian Institute of Health Research (203745). S.M.V. received salary support from the Ontario Institute of Cancer Research (OICR) and the London Health Sciences Foundation (LHSF) Helen and Andy Spriet funds. M.MYH. is funded by grant 1156124 Doctoral Award from the Cancer Research Society and the Canadian Institutes of Health Research-Institute for Cancer Research, Canadian Graduate Scholarship-Masters and Ontario Graduate Scholarship. A.S.A. is supported by an Undergraduate Student Research Award grant from the Natural Sciences and Engineering Research Council of Canada. Extended Data Fig. 9 was created in BioRender: Hong, M. (2025): https://BioRender.com/qacqx02. We also thank J. Wargo and N. Ajami from The University of Texas MD Anderson Cancer Center for providing access to the metagenomics and clinical data published in ref. 65, which were used to address reviewers’ comments.

Author information

These authors contributed equally: Ricardo Fernandes, Behnam Jabbarizadeh, Adnan Rajeh.

Authors and Affiliations

Division of Medical Oncology, Department of Oncology, Western University, London, Ontario, Canada

Ricardo Fernandes, Adnan Rajeh, Scott Ernst, Eric Winquist & John G. Lenehan
Verspeeten Family Cancer Centre, London Health Sciences Centre Research Institute, London Health Sciences Centre, London, Ontario, Canada

Ricardo Fernandes, Behnam Jabbarizadeh, Adnan Rajeh, John G. Lenehan & Saman Maleki Vareki
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

Megan M Y Hong, Kelly J. Baines, Anorin Shadi Ali & Saman Maleki Vareki
National Research Council Canada, Human Health Therapeutics, Halifax, Nova Scotia, Canada

Susanne Penny & Devanand M. Pinto
Division of Experimental Oncology, Department of Oncology, Western University, London, Ontario, Canada

Rene Figueredo & Saman Maleki Vareki
Division of Infectious Diseases, Department of Medicine, Western University, London, Ontario, Canada

Seema Nair Parvathy & Michael S. Silverman
Lawson Research Institute, London, Ontario, Canada

Seema Nair Parvathy & Michael S. Silverman
Division of Infectious Diseases, St. Joseph’s Health Care, London, Ontario, Canada

Seema Nair Parvathy & Michael S. Silverman
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

Devanand M. Pinto
Department of Medical Biophysics, Western University, London, Ontario, Canada

Saman Maleki Vareki
Ontario Institute of Cancer Research, Toronto, Ontario, Canada

Saman Maleki Vareki

Contributions

S.M.V. conceived the study. S.M.V. and R.F. designed the trial and co-wrote the trial protocol and secured funding. S.M.V. designed and supervised translational studies. R.F., E.W., A.R. and S.E. recruited and/or treated patients. B.J., M.MYH., K.J.B., A.S.A., R.F., J.G.L., A.R., D.P. and S.P. collected and/or analyzed the data. S.N.P. and M.S.S. prepared and conducted FMT. S.M.V. wrote the first draft and approved the final draft. All authors provided comments and approved the manuscript.

Corresponding author

Correspondence to Saman Maleki Vareki.

Ethics declarations

Competing interests

S.M.V., M.S.S., S.N.P. and B.J. are co-founders of LND Therapeutics Inc., which holds the rights to LND101. S.M.V. and M.S.S. report US Patent application no. 63/913,940 related to FMT donor screening. S.M.V. reports a grant from Microviable Therapeutics outside the submitted work as well as consulting fees from Kanvas Biosciences and FedBio. R.F. has the following disclosures: advisory board or honoraria: Merck, Ipsen, Eisai, EMD Serono, Astellas, Novartis, Janssen, Pfizer, Bristol Myers Squibb and Bayer; travel grant: Janssen. E.W. declares research grants from Lilly, Novartis and Merck; consulting fees from Bayer, Bristol Myers Squibb, Eisai, EMD, Serono, Merck and Roche; and honoraria from EMD Serono. E.W. also declares travel support from Eisai. M.S.S. has served on the advisory board of Ferring Pharmaceuticals. All other authors declare no conflicts of interest.

Peer review

Peer review information

Nature Medicine thanks Diwakar Davar, Sumanta Pal 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.