FMT combined with atezolizumab-bevacizumab in hepatocellular carcinoma refractory to immunotherapy: an open label, single-arm, phase II pilot study
Abstract
Fecal microbiota transplantation (FMT) may help to overcome resistance to immunotherapy. In this single-center, single-arm phase II hypothesis-generating pilot study (FAB-HCC), we included 12 patients with advanced hepatocellular carcinoma (HCC) who progressed on atezolizumab plus bevacizumab. Patients received a single FMT via colonoscopy from a donor with HCC who responded to anti-PD-1 treatment or a healthy donor, combined with atezolizumab plus bevacizumab. The primary endpoint was safety as measured by incidence and severity of treatment-related adverse events (TRAEs). Secondary endpoints included radiological response and survival. Grade 3-4 TRAEs included arterial hypertension ( n = 5) and proteinuria ( n = 3), both related to bevacizumab, and diarrhea ( n = 1), related to FMT. No serious TRAEs were observed. Objective response rate was 33% ( n = 4/12) and median progression-free survival was 6.9 (95%CI, 3.0-10.8) months. Following FMT, recipient microbiome composition appeared more similar to that of the donor, and healthy donor FMT seemed to be associated with higher engraftment. FMT appeared to be associated with enrichment of response-associated and loss of deleterious gut bacteria. Circulating PD-1 ⁺ CD8 ⁺ T cells decreased and CD32b ⁺ CD14 high CD16 low monocytes increased following FMT plus immunotherapy. Phage-display immunoprecipitation sequencing revealed that antibody repertoire stability, rather than global diversity or composition, changed over time. Taken together, FMT combined with atezolizumab plus bevacizumab was safe and associated with a high response rate in patients with atezolizumab plus bevacizumab-refractory HCC. Given the limited sample size, these findings need cautious interpretation and confirmation in larger, adequately powered trials. ClinicalTrials.gov identifier: NCT05750030.
Related
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- Real-world evidence for atezolizumab with bevacizumab for unresectable hepatocellular carcinoma: a multicentre UK Midlands cohort
- Prognostic Significance of Response Dynamics in Atezolizumab plus Bevacizumab-Treated Hepatocellular Carcinoma: A Multicenter Real-World Validation Study.
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BibTeX
@article{pomej2026combined,
title = {{FMT combined with atezolizumab-bevacizumab in hepatocellular carcinoma refractory to immunotherapy: an open label, single-arm, phase II pilot study}},
author = {Katharina Pomej and Adrian Frick and Bernhard Scheiner and Maximilian Baumgartner and Klaus G. Schmetterer and Carlos S. Reyna-Blanco and Lorenz Balcar and Larissa Pajancic and Abelina Kreuter and Joana Séneca and Bela Hausmann and Thomas Köcher and Melanie Prinzensteiner and Katharina Lampichler and Nataliya Rohr-Udilova and Adrija Chakrabarty and Anton Klotz and Annika C. Lampl and Kerstin Zinober and Katharina Regnat and Michael Trauner and David Berry and Dietmar Tamandl and Thomas Vogl and Christoph Gasche and Matthias Pinter},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78219-z},
url = {https://www.nature.com/articles/s41467-026-78219-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - FMT combined with atezolizumab-bevacizumab in hepatocellular carcinoma refractory to immunotherapy: an open label, single-arm, phase II pilot study
AU - Katharina Pomej
AU - Adrian Frick
AU - Bernhard Scheiner
AU - Maximilian Baumgartner
AU - Klaus G. Schmetterer
AU - Carlos S. Reyna-Blanco
AU - Lorenz Balcar
AU - Larissa Pajancic
AU - Abelina Kreuter
AU - Joana Séneca
AU - Bela Hausmann
AU - Thomas Köcher
AU - Melanie Prinzensteiner
AU - Katharina Lampichler
AU - Nataliya Rohr-Udilova
AU - Adrija Chakrabarty
AU - Anton Klotz
AU - Annika C. Lampl
AU - Kerstin Zinober
AU - Katharina Regnat
AU - Michael Trauner
AU - David Berry
AU - Dietmar Tamandl
AU - Thomas Vogl
AU - Christoph Gasche
AU - Matthias Pinter
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78219-z
UR - https://www.nature.com/articles/s41467-026-78219-z
AB - Fecal microbiota transplantation (FMT) may help to overcome resistance to immunotherapy. In this single-center, single-arm phase II hypothesis-generating pilot study (FAB-HCC), we included 12 patients with advanced hepatocellular carcinoma (HCC) who progressed on atezolizumab plus bevacizumab. Patients received a single FMT via colonoscopy from a donor with HCC who responded to anti-PD-1 treatment or a healthy donor, combined with atezolizumab plus bevacizumab. The primary endpoint was safety as measured by incidence and severity of treatment-related adverse events (TRAEs). Secondary endpoints included radiological response and survival. Grade 3-4 TRAEs included arterial hypertension ( n = 5) and proteinuria ( n = 3), both related to bevacizumab, and diarrhea ( n = 1), related to FMT. No serious TRAEs were observed. Objective response rate was 33% ( n = 4/12) and median progression-free survival was 6.9 (95%CI, 3.0-10.8) months. Following FMT, recipient microbiome composition appeared more similar to that of the donor, and healthy donor FMT seemed to be associated with higher engraftment. FMT appeared to be associated with enrichment of response-associated and loss of deleterious gut bacteria. Circulating PD-1 ⁺ CD8 ⁺ T cells decreased and CD32b ⁺ CD14 high CD16 low monocytes increased following FMT plus immunotherapy. Phage-display immunoprecipitation sequencing revealed that antibody repertoire stability, rather than global diversity or composition, changed over time. Taken together, FMT combined with atezolizumab plus bevacizumab was safe and associated with a high response rate in patients with atezolizumab plus bevacizumab-refractory HCC. Given the limited sample size, these findings need cautious interpretation and confirmation in larger, adequately powered trials. ClinicalTrials.gov identifier: NCT05750030.
SN - 2041-1723
ER -