MICROBIOME
Research type
Research Study
Full title
MICROBIOME: A first in human, phase 1 safety study in two parts to determine the safety, tolerability and anti-cancer immuno-modulatory effects of MRx0518 in patients with solid tumours awaiting surgical removal of the tumour.
IRAS ID
234395
Contact name
Jonathan Krell
Contact email
Sponsor organisation
Imperial College London
Eudract number
2017-004300-21
Duration of Study in the UK
3 years, 11 months, 29 days
Research summary
Research Summary
A first in human, single site study, which aims to determine the safety and tolerability of the novel biotherapeutic compound, MRx0518, to examine its use as an anti-cancer and immune system modulating agent in patients with a range of solid tumours, over 2 years.
MRx0518 is composed of the bacterium, Enterococcus gallinarum which is found in the gastrointestinal tract of many humans and is predicted, from preclinical studies, to produce beneficial effects in humans.
Following successful screening, patients who have been diagnosed with melanoma, breast, ovarian, uterine, prostate, urethra, bladder, renal, lung or head and neck cancer, who are amenable to surgical resection, will receive MRx0518 or placebo until surgery to remove the tumour. Post treatment tissue samples will be collected from surgical specimens. Plasma, peripheral blood mononuclear cells (PBMCs), faeces and urine will be collected pre-treatment and periodically for up to 30 days after the last dose of MRx0518 or placebo. Following surgery, patients will attend 30 day, 6 month, 12 month and 24 month follow up visits.
IMP will be orally administered twice daily for 2-4 weeks prior to surgery in two parts. Part A will comprise of a non-randomised, open label MRx0518 that is a preliminary safety assessment, which will be undertaken in 20 patients. Following successful evaluation by the data safety and monitoring board (DSMB), the study will continue to recruit a further 100 patients to Part B of the trial. Part B will be placebo controlled, in which patients will be randomised in a double blinded fashion in a 4:1 ratio of MRx0518:placebo. In total, 120 patients will be recruited into the study (20 from part A and 100 from part B).
Lay summary of study results:
Part A of the trial was completed following recruitment of 17 patients. However, the COVID-19 outbreak in 2020 resulted in the significant disruption of clinical activities (including cancer treatment) and the ability to run clinical trials. Normal patient visitation to the hospital was heavily restricted (in line with Department of Health guidance) significantly disrupting data collection for this study. Therefore complete datasets are only available for 8 out of the 17 patients enrolled onto the study. Following the Independent Data Committee review of the available data it was deemed there was insufficient data to formalise conclusions about the safety and tolerability of MRx0518 in this group of patients. However, there were no reported SAEs, SUSARs and grade 3 or 4 toxicity in subjects. 29 AEs were recorded, of which 28 were considered mild. Whilst we are not able to draw definitive conclusions on the safety and tolerability of MRx0518 in cancer patients, the data we did manage to collect looked encouraging.
Upon completion of Part A recruitment the study was paused as the funder (4D Pharma) wished to await results from the translational analysis. There were plans to modify Part B based on this analysis and further pre-clinical data gleaned during the study period. However, unfortunately the funder went into administration on Q2 of 2022 and was forced to terminate Part B. 4D Pharma was sold off in Q2 of 2023 Plans to move forward with Part B of the study were therefore abandoned.
URL to summary results:
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East of England - Cambridge East Research Ethics Committee
REC reference
18/EE/0091
Date of REC Opinion
5 Jun 2018
REC opinion
Further Information Favourable Opinion