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First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO Trial)

Spreafico, A. and Heirali, A. A. and Araujo, D. V. and Tan, T. J. and Oliva, M. and Schneeberger, P. H. H. and Chen, B. and Wong, M. K. and Stayner, L. A. and Hansen, A. R. and Saibil, S. D. and Wang, B. X. and Cochrane, K. and Sherriff, K. and Allen-Vercoe, E. and Xu, W. and Siu, L. L. and Coburn, B.. (2023) First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO Trial). Ann Oncol, 34 (6). pp. 520-530.

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Abstract

BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICI) in humans, and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use. PATIENTS AND METHODS: We conducted an early phase clinical trial of a cultivated, orally-delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic-4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors. RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes, however, differences in MET4-species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids. CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser)
UniBasel Contributors:Schneeberger, Pierre
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1569-8041 (Electronic)0923-7534 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:06 Jul 2023 09:30
Deposited On:06 Jul 2023 09:30

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