What side effects are associated with this type of intervention?

Common treatments for solid tumors, particularly those involving immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, can cause a range of side effects. These include immune-related adverse events (irAEs) such as inflammation in various organ systems, which may manifest as colitis, pneumonitis, hepatitis, endocrinopathies, and skin reactions. Probiotics, when used as an adjunct to enhance immune response, are generally well-tolerated but can occasionally cause gastrointestinal symptoms like bloating and gas. Combining these treatments aims to improve efficacy while monitoring for and managing potential side effects.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors (ICIs) for the treatment of solid tumors, including pembrolizumab, nivolumab, and atezolizumab. These drugs target proteins such as PD-1, PD-L1, and CTLA-4 to enhance the body's immune response against cancer cells. Pembrolizumab, for example, has been approved for various solid tumors, including melanoma and non-small cell lung cancer. While the use of probiotic strains to enhance the immune response is still under investigation, the combination of ICIs with other therapies represents a significant advancement in the treatment of solid tumors.

What other types of research exist?

Promising novel alternatives to MET-4 for solid tumor patients include: 1) Autologous dendritic cell-based immunotherapy, 2) Bispecific antibodies, 3) PSMA-targeting CAR T-cell therapies, and 4) High-dose interleukin-2 therapy. These approaches have demonstrated potential in enhancing immune responses and improving clinical outcomes in solid tumor patients.

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MET-4 for Cancer (MET4-IO Trial)

Phase 2 & 3

Waitlist Available

Led By Lillian Siu, MD

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

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.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if adding beneficial gut bacteria to a standard cancer treatment can help the immune system fight cancer better. It focuses on patients who are already receiving cancer treatment but are not responding well. The beneficial bacteria may boost the immune response, enhancing the effectiveness of the cancer medicine.

Who is the study for?

Adults with advanced solid tumors who are either starting or already on anti-PD-1/PD-L1 immunotherapy, not part of another clinical trial. They must be able to provide tissue samples, stool and blood for analysis, have measurable disease, and a performance status of 0-2. Women must not be pregnant. Those with gastrointestinal disorders affecting absorption cannot join.

What is being tested?

The study is testing MET-4's safety and its ability to integrate into the body when used with standard immune checkpoint inhibitors (ICIs). Participants are divided into groups: one receiving MET-4 plus ICI therapy; others getting only ICI therapy; some who've seen disease progression on ICIs may also receive MET-4.

What are the potential side effects?

Potential side effects include those commonly associated with fecal microbiome transplants such as digestive upset, infection risk due to altered gut bacteria, and any typical reactions related to immune checkpoint inhibitors like fatigue or skin issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of my waking hours.

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I am currently on a PD-1 or PD-L1 inhibitor treatment, not as part of another clinical trial.

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I am starting on a specific immune therapy not part of another clinical trial.

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My cancer is advanced, has spread, and cannot be cured.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Changes in relative abundance of immunotherapy-responsiveness associated MET-4 strains between baseline and approximately day 12

Cumulative relative abundance of immunotherapy-responsiveness associated species at day 12 of MET-4

Number of participants with treatment-related adverse events assessed by CTCAE v.5.0

Secondary study objectives

Bacterial taxonomic diversity between baseline and follow-up samples

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)

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).

Other study objectives

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

Characterization of tumor microenvironment of archived tumor samples

Dynamic measures of microbiome as correlates of blood immune profiling

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Group DExperimental Treatment1 Intervention

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.

Group II: Group CExperimental Treatment1 Intervention

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.

Group III: Group BExperimental Treatment1 Intervention

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.

Group IV: Group A: Safety CohortExperimental Treatment1 Intervention

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

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cancer cells, but it can also affect normal cells, leading to side effects. Targeted therapy aims at specific molecules involved in cancer growth and survival, offering a more precise approach with potentially fewer side effects. Immunotherapy, including immune checkpoint inhibitors, enhances the body's immune response against cancer cells. The MET-4 trial explores the use of probiotic strains to boost the immune system, potentially improving the efficacy of immunotherapy. This matters for solid tumor patients as enhancing the immune response can lead to better control of tumor growth and potentially improve survival rates.

The anticancer immune response: indispensable for therapeutic success?