Feasibility Study of MET-4: Evaluating Fecal Microbiome Effects in Immunotherapy Patients

NCT03686202 | Active Not Recruiting Phase 2

• 1 other identifier: MET4-IO-001
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

All Solid Tumors

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (3)

• 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).

  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)

  2 years

• Bacterial taxonomic diversity between baseline and follow-up samples

  2 years

Other Outcomes (5)

• Response

  2 years

• Progression free survival

  2 years

• Changes in immune cell subsets in the systemic circulation in response to MET-4 through serial blood sampling.

  24 weeks

Study Arms (4)

Group A: Safety Cohort

EXPERIMENTAL

Subjects with advanced solid tumors already on ICI will receive treatment with MET-4 in addition to SOC ICI. MET-4 is administered orally as an initial daily loading dose (5g) of MET-4 over 2 days followed by a daily maintenance dose (1.5g) of MET-4 and will be continued until unacceptable toxicity, progression of disease

Biological: MET-4

Group B

EXPERIMENTAL

Eligible subjects with advanced solid tumors starting ICI will be randomised in a 3:1 ratio stratifying for prior IO exposure, to receive MET-4 together with any approved PD-1/PD-L1 inhibitor as per SOC or control group. There will be a run-in period for subjects in the MET-4 treatment group. Following the run-in period of ICI therapy, subjects will be administered the same MET-4 dose as subjects in group A.

Biological: MET-4

Group C

EXPERIMENTAL

In group C, eligible subjects with advanced solid tumors whom are already on ICI with first unconfirmed PD on evaluation scans per investigator's assessment, will be randomised in a 1:1 ratio to receive MET-4 in addition to the PD-1/PD-L1 inhibitor as per SOC or control group. These subjects must be clinically stable and are to be continued on ICI at the discretion of the investigator. There will be no run-in period for this cohort. Subjects will be administered the same MET-4 dose as subjects in groups A and B.

Biological: MET-4

Group D

EXPERIMENTAL

In group D, eligible subjects with stage III or resected stage IV melanoma who are to start adjuvant ICI, will be randomized in a 1:1 ratio to receive MET-4 in addition to anti-PD1 antibody +/- anti-CTLA4 antibody as per SOC or control group. Patients will be stratified per BRAF mutation status. Subjects will be administered the same MET-4 dose as subjects in groups A, B and C. MET-4 will be initiated as run-in for a minimum of 1 week, and maximum of 2 weeks before ICI administration. MET-4 will be continued until unacceptable toxicity, confirmed PD by RECIST v1.1 or completion of 1 year of ICI, whichever occurs earlier. Subjects in the control arms of groups B, C and D will be treated with ICI therapy as per institution standard of care without MET-4.

Biological: MET-4

Interventions

MET-4 BIOLOGICAL

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.

Group A: Safety Cohort; Group B; Group C; Group D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• NuBiyota: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Study Officials

• Lillian Siu, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

• Anna Spreafico, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: September 26, 2018
• Study Start: November 30, 2018
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)