This study is designed to assess the safety, tolerability and engraftment (cumulative relative abundance) of MET-4 strains when given in combination with immune checkpoint inhibitors (ICIs). There will be a safety cohort (group A) of 5 subjects which will receive MET-4 in addition to standard of care (SOC) ICI. After the safety cohort, 40 patients will be enrolled in group B which will be randomized to MET4 with SOC ICI vs. control group with SOC ICI only. Group C will enroll 20 patients who have already started on SOC ICI and have had first unconfirmed progression of disease and expected to continue with standard ICI treatment. These patients will be randomized to continue receiving standard ICI alone, or SOC ICI with MET4.
Human associated microorganisms (the microbiota) inhabit virtually all surfaces of the human body. The gut is densely colonized by the microbiota which aids in the digestion. Animal and human observational and experimental evidence show a link between gut microbiota and the activation, regulation and function of the immune system. Pre-clinical studies in mouse models have linked the gut microbiota to efficacy of anticancer therapies. Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an alternative to fecal transplantation. MET consists of a defined mixture of pure live cultures of intestinal bacteria isolated from a stool sample of a healthy donor. This study is designed to assess the safety, tolerability and engraftment (cumulative relative abundance) of MET-4 strains when given in combination with immune checkpoint inhibitors (ICIs).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an alternative to fecal transplantation. Unlike donor stool used in fecal transplants, which are incompletely characterised complex communities of microbes and associated metabolites and fecal material, MET consists of a defined mixture of pure live cultures of intestinal bacteria isolated from a stool sample of a healthy donor.
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Cumulative relative abundance of immunotherapy-responsiveness associated species at day 12 of MET-4
Fecal microbial abundance measured via qPCR and Nanostring analysis of stool at approximately day 12
Time frame: Approximately 12 days
Changes in relative abundance of immunotherapy-responsiveness associated MET-4 strains between baseline and approximately day 12
Microbiome gene sequencing of stool at baseline and approximately day 12 post first dose
Time frame: Approximately 12 days
Number of participants with treatment-related adverse events assessed by CTCAE v.5.0
Related toxicities and severity collected as per CTCAE version 5.0
Time frame: 2 years
Cumulative relative abundance of immunotherapy-responsiveness associated species at later MET-4 or control time points (approximately 24 weeks and/or 1-2 weeks following the end of treatment).
Fecal microbial abundance measured via qPCR and Nanostring analysis of stool at baseline and week 24 after first dose and EOT.
Time frame: 2 years
Changes in relative abundance of immunotherapy-responsiveness associated MET-4 strains between baseline and later MET-4 or control timepoints (approximately 24 weeks and/or 1-2 weeks following the end of treatment)
Microbiome gene sequencing of stool at baseline and week 24 after first dose and EOT.
Time frame: 2 years
Bacterial taxonomic diversity between baseline and follow-up samples
Microbiome gene sequencing of stool at baseline, day 10-16 post first dose, week 3-4 post first dose, and week 24 after first dose and EOT.
Time frame: 2 years
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