Feasibility Study of Microbial Ecosystem Therapeutics (MET-4) to Evaluate Effects of Fecal Microbiome in Patients on ImmunOtherapy

All Solid Tumors Clinical Trial

— MET4-IO  

Official title:

Feasibility Study of Microbial Ecosystem Therapeutics (MET-4) to Evaluate Effects of Fecal Microbiome in Patients on ImmunOtherapy (MET4-IO)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03686202
• Other study ID #: MET4-IO-001
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 30, 2018
• Est. completion date: December 1, 2025

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written and voluntary informed consent

• Age >=18 years, male or female

• Histologically or cytological documented locally-advanced or metastatic solid malignancy which is incurable.

• Group A: Is already on treatment with monotherapy anti-PD-1 or PD-L1 immune checkpoint inhibitor, not in the context of a therapeutic clinical trial.

Group B: Is intended to start on treatment with monotherapy anti-PD-1 or PD-L1 immune checkpoint inhibitors as considered appropriate by treatment physician, and not in the context of a therapeutic clinical trial.

Group C: Is already on treatment with monotherapy anti-PD-1 or PD-L1 immune checkpoint inhibitor, not in the context of a therapeutic clinical trial with first unconfirmed PD on evaluation scan per investigator's assessment.

• Be willing to provide 10-15 unstained slides of archival tissue sample. Subjects who decline or have not sufficient archived tissue samples may still enroll if all other criteria are eligible.

• Be willing and able to provide stool and blood specimen for analyses at protocol specified time points.

• Have measurable disease based on RECIST 1.1

• Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale.

• Prior therapy with any immunotherapy allowed.

• Not pregnant for females of child bearing potential as indicated by negative serum or urine pregnancy test within 72 hours of study start.

Exclusion Criteria:

• Subjects unable to swallow orally administered medications or any subjects with gastrointestinal disorders likely to interfere with absorption (e.g. bowel obstruction, short gut syndrome, blind loop syndrome, ileostomy etc). Subjects with colostomies may be enrolled.

• Any condition that, in the opinion of the Investigator, would interfere with subject safety, or evaluation of the collected specimen and interpretation of study result.

• Pregnant or planning to get pregnant in the next 6 months.

Related Conditions & MeSH terms

• All Solid Tumors

Intervention

Biological:
• MET-4
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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	NuBiyota

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Response	Objective response rates of ICI when given in combination with MET-4 as measured per RECIST v1.1 and iRECIST	2 years
Other	Progression free survival	Time from randomization until disease progression or death as measured per RECIST v.1.1 and iRECIST	2 years
Other	Changes in immune cell subsets in the systemic circulation in response to MET-4 through serial blood sampling.	Flow cytometry/CyTOF of blood at baseline, 6-8 weeks post first dose of MET, 24 weeks post first dose	24 weeks
Other	Characterization of tumor microenvironment of archived tumor samples	Standard immunohistochemistry (IHC) of baseline archival tumor	2 years
Other	Dynamic measures of microbiome as correlates of blood immune profiling	Flow cytometry/CyTOF of blood at baseline, week 3-4 post first dose of MET, and week 24 post first dose, and stool microbiome gene profiling at baseline, 10-16 days first dose of MET, week 3-4 post first dose, week 24 post first dose and end of treatment.	2 years
Primary	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	Approximately 12 days
Primary	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	Approximately 12 days
Primary	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	2 years
Secondary	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.	2 years
Secondary	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.	2 years
Secondary	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.	2 years