All Solid Tumors
Conditions
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.
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).
Interventions
BIOLOGICALMET-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.
Sponsors
University Health Network, Toronto
NuBiyota
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative relative abundance of immunotherapy-responsiveness associated species at day 12 of MET-4 | Approximately 12 days | Fecal microbial abundance measured via qPCR and Nanostring analysis of stool at approximately day 12 |
| Changes in relative abundance of immunotherapy-responsiveness associated MET-4 strains between baseline and approximately day 12 | Approximately 12 days | Microbiome gene sequencing of stool at baseline and approximately day 12 post first dose |
| Number of participants with treatment-related adverse events assessed by CTCAE v.5.0 | 2 years | Related toxicities and severity collected as per CTCAE version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Fecal microbial abundance measured via qPCR and Nanostring analysis of stool at baseline and week 24 after first dose and EOT. |
| 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 | Microbiome gene sequencing of stool at baseline and week 24 after first dose and EOT. |
| Bacterial taxonomic diversity between baseline and follow-up samples | 2 years | 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. |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORLillian Siu, MD
Princess Margaret Cancer Centre
PRINCIPAL_INVESTIGATORAnna Spreafico, MD
Princess Margaret Cancer Centre
Outcome results
None listed