First-in-class microbial ecosystem therapeutics 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumours (MET4-IO Trial)

The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICI) in humans, and causally implicated in ICI responsiveness in animal models. Therapeutic augmentation of the microbiome in ICI recipients is being investigated in multiple ongoing human clinical trials. 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 and assessed safety, tolerability and ecological responses in patients with advanced solid tumors. Examine the bacterial cumulative relative abundance of immunotherapy-responsiveness associated with MET4 strains between baseline, day 12 (during treatment), week 24 (after treatment) and to determine the bacterial taxonomic diversity between baseline and follow-up samples. 16S rRNA gene amplicon sequencing was used for identification, classification and quantitation of microbes within complex patient fecal mixtures (human gut mircobiome)