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All Solid TumorsPhase 2/3MET4-IONCT03686202

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

A Phase 2/3 study testing MET-4 in people with All Solid Tumors, run by University Health Network, Toronto at 1 site in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
All Solid Tumors
What is being tested?
MET-4
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
1 siteCanada
Study dates
30 Nov 2018to 1 Dec 2026
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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

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.

Read the detailed 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).

Being tested
MET-4

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MET-4Biological

    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.

Study groups in NCT03686202
Study groupRoleWhat they receive
Group A: Safety CohortExperimentalSubjects 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
Receives: Biological: MET-4
Group BExperimentalEligible 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.
Receives: Biological: MET-4
Group CExperimentalIn 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.
Receives: Biological: MET-4
Group DExperimentalIn 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.
Receives: Biological: MET-4

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Approximately 12 days

  2. 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

    Measured: Approximately 12 days

  3. 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

    Measured: 2 years

Secondary outcomes (3)

  1. 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.

    Measured: 2 years

  2. 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.

    Measured: 2 years

  3. 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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2018
  2. Study start30 Nov 2018
  3. Primary completion1 Dec 2024
  4. Study completion1 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
65 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03686202
Sponsor's protocol ID
MET4-IO-001
Acronym
MET4-IO
Status last verified
Sep 2026
First submitted
24 Sep 2018
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing MET-4 in people with All Solid Tumors, run by University Health Network, Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative relative abundance of immunotherapy-responsiveness associated species at day 12 of MET-4 (time frame: Approximately 12 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03686202.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

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