MET-4 for Cancer

(MET4-IO Trial)

Overseen By Lillian Siu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University Health Network, Toronto

Must be taking: Immune checkpoint inhibitors

Disqualifiers: Gastrointestinal disorders, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment, MET-4, combined with immune checkpoint inhibitors (ICIs) for individuals with advanced cancer. The study divides participants into groups to test MET-4's impact when added to standard cancer treatments. Participants will receive either MET-4 with their usual treatment or just their usual treatment to determine if MET-4 makes a difference. This trial suits individuals with advanced solid tumors who are about to start or are already receiving ICIs as their main treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it seems that participants are expected to continue their standard immune checkpoint inhibitor treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that MET-4, a new treatment, has been tested for safety with immune checkpoint inhibitors (ICIs), a common cancer treatment. Studies indicate that MET-4 is generally well-tolerated by patients with advanced solid tumors. Earlier research found that most patients did not experience severe side effects from MET-4. These studies primarily aimed to assess how patients handled the treatment and its effects on their bodies.

Although MET-4 is still undergoing testing, its presence in later trial phases suggests it demonstrated a reasonable level of safety in earlier trials. For those considering participation in a MET-4 trial, this information may be useful. Always consult a healthcare provider to understand what this means personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

MET-4 is unique because it combines with standard immunotherapy treatments, like anti-PD1 and anti-CTLA4 antibodies, to potentially enhance their effectiveness for cancer patients. Unlike most treatments that target tumors directly, MET-4 may modulate the immune system to improve the efficacy of existing immunotherapies. Researchers are excited because MET-4 could offer a new approach to treating advanced solid tumors, potentially increasing the duration and depth of responses to immunotherapy. Additionally, MET-4's oral administration makes it a convenient option for patients.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that MET-4 might enhance the effectiveness of immune checkpoint inhibitors (ICIs), which help the immune system fight cancer cells. In this trial, participants will join different groups to evaluate how well MET-4 works with anti-PD1 therapies for treating advanced cancers like melanoma. Early findings suggest that MET-4 could improve the body's response to these treatments, possibly leading to better outcomes. The current focus is on understanding how well MET-4 can work with these existing cancer therapies to benefit more patients. ^{1 4 5 6 7}

Who Is on the Research Team?

Lillian Siu, MD

Principal Investigator

Princess Margaret Cancer Centre

Anna Spreafico, MD PhD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

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

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

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.

I can swallow pills and don't have gut issues affecting drug absorption, except I may have a colostomy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

MET-4 is initiated as a run-in for a minimum of 1 week, and maximum of 2 weeks before ICI administration

1-2 weeks

Treatment

Participants receive MET-4 in combination with immune checkpoint inhibitors (ICIs) until unacceptable toxicity, confirmed progression of disease, or completion of 1 year of ICI

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MET-4

Trial Overview 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.

How Is the Trial Designed?

Group I: Group D Experimental Treatment 1 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 C Experimental Treatment 1 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 B Experimental Treatment 1 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 Cohort Experimental Treatment 1 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

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

NuBiyota

Collaborator

Trials

9

Recruited

240+

Published Research Related to This Trial

In a phase II trial, capmatinib, a MET inhibitor, showed a high response rate of 72% in treatment-naïve patients, indicating its potential effectiveness in early-stage treatment.

For previously treated patients, the response rate was lower at 39.1%, and common side effects included peripheral edema, nausea, and vomiting, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capmatinib Triggers Responses in NSCLC. [2019]

AMG 337, a MET inhibitor, was well-tolerated in a small study of 11 Asian patients with advanced solid tumors, showing no dose-limiting toxicities and common side effects like headache (73%) and nausea (45%).

The pharmacokinetics of AMG 337 were consistent with previous studies in Western populations, and while one patient experienced a partial response, the study was terminated early, indicating the need for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 study evaluating AMG 337 in Asian patients with advanced solid tumors. Yasui, H., Go, N., Yang, H., et al.[2022]

AMG 337, an oral MET inhibitor, was found to be tolerable with manageable side effects, establishing a maximum tolerated dose of 300 mg once daily in a study involving 111 patients with advanced solid tumors.

The treatment showed a promising objective response rate of 29.6% in patients with MET-amplified tumors, suggesting potential efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors. Hong, DS., LoRusso, P., Hamid, O., et al.[2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00088-1/fulltext

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) ... MET4-IO is a single-center investigator-initiated clinical trial designed to evaluate the safety, tolerability and engraftment of MET4 in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10195722/

Features and Long-Term Outcomes of Stage IV Melanoma ... Another publication showed that 16% of patients with advanced melanoma treated with pembrolizumab achieved a CR and 87.6% exhibited ongoing ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0923753423000881

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) ... The efficacy of MET4 with anti-PD1 will be explored in a phase II study in advanced head and neck cancer patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11559077/

Top advances of the year: Melanoma - PMC The median overall survival (OS) was 13.9 months, with a 12-month OS rate of 54.0%, and the median progression-free survival (PFS) was 4.1 months, with a 12- ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK_438654

Curing Stage IV Melanoma: Where Have We Been and ... Long-term outcomes reported 6.5-year overall survival and melanoma-specific survival of 49% and 56% for ipinivo, 42% and 48% for nivolumab, and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4811023/

Survival, Durable Tumor Remission, and Long-Term Safety in ... Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

7. jitc.bmj.com jitc.bmj.com/content/13/3/e010681

Microbial Ecosystem Therapeutics 4 (MET4) elicits ... MET4-IO study and collection time points. Individuals with solid tumors were enrolled into MET4-IO, a clinical study that assessed the safety, ...