805 Safety and emerging evidence of immune modulation of the live biotherapeutic MRx0518 in the neoadjuvant setting for patients awaiting surgical removal of solid tumours
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Author(s)
Type
Journal Article
Abstract
Background The gut microbiome has emerged as a promising innovative therapeutic target for immune-stimulation treatment of solid tumours. MRx0518 is a novel, gut microbiome-derived oral live biotherapeutic. It has potent anti-tumorigenic efficacy in the preclinical setting including murine models of lung (LLC1), kidney (Renca) and breast (EMT6) cancer.1 In these models, a significant reduction in tumour growth has been demonstrated, including induction of immunostimulatory responses with tumour infiltration of NK cells, CD8+ and CD4+ T-cells. MRx0518 is under investigation in various oncological settings, including in combination with immune checkpoint inhibitors (NCT03637803) and radiotherapy (NCT04193904).
Methods Treatment naïve patients were recruited from April 2019 to February 2020. Patients were eligible if they received a histologically confirmed diagnosis of cancer (solid tumours) scheduled for surgical resection. Patients received 1 capsule of MRx0518 (1x1010 to 1x1011 CFU) twice daily from inclusion until the day preceding surgery (maximum 28 days therapy). The primary study outcome is to evaluate safety and tolerability of MRx0518 monotherapy in treatment naïve patients. Additional exploratory outcomes including identifying surrogate biomarkers of efficacy, microbiome analysis, effect on metabonomic markers and identification of histological and genomic alterations in paired pre-treatment (diagnostic biopsy) and post-treatment (surgical specimen) samples.
Results In part A, 17 patients received treatment, across tumour groups including breast (n=8), prostate (n=4), uterine (n=3), melanoma (n=1) and bladder (n=1). MRx0518 was well tolerated by all, with no grade 3/4 CTCAE toxicity reported, no severe adverse effects or treatment discontinuations. All patients proceeded to surgery, however the COVID-19 pandemic delayed surgery in 3 cases.
Analysis of the first 5* patient paired samples utilising the NanoString Pan Cancer IO 360TM Gene Expression panel has demonstrated significant changes in gene expression profiles in 48 genes (p
Conclusions This study has demonstrated the safety and tolerability of the live biotherapeutic MRx0518 in treatment naïve cancer patients. Exploratory analyses of post-treatment samples has echoed preclinical observations of increased infiltration of immune cells following treatment and will undergo further validation. Part B will focus on investigating efficacy in a further 100 treatment naïve patients with a placebo-controlled arm.
Trial Registration NCT03934827
Ethics Approval The study was approved by East of England - Cambridge East Research Ethics Committee approval number 18/EE/0091
Methods Treatment naïve patients were recruited from April 2019 to February 2020. Patients were eligible if they received a histologically confirmed diagnosis of cancer (solid tumours) scheduled for surgical resection. Patients received 1 capsule of MRx0518 (1x1010 to 1x1011 CFU) twice daily from inclusion until the day preceding surgery (maximum 28 days therapy). The primary study outcome is to evaluate safety and tolerability of MRx0518 monotherapy in treatment naïve patients. Additional exploratory outcomes including identifying surrogate biomarkers of efficacy, microbiome analysis, effect on metabonomic markers and identification of histological and genomic alterations in paired pre-treatment (diagnostic biopsy) and post-treatment (surgical specimen) samples.
Results In part A, 17 patients received treatment, across tumour groups including breast (n=8), prostate (n=4), uterine (n=3), melanoma (n=1) and bladder (n=1). MRx0518 was well tolerated by all, with no grade 3/4 CTCAE toxicity reported, no severe adverse effects or treatment discontinuations. All patients proceeded to surgery, however the COVID-19 pandemic delayed surgery in 3 cases.
Analysis of the first 5* patient paired samples utilising the NanoString Pan Cancer IO 360TM Gene Expression panel has demonstrated significant changes in gene expression profiles in 48 genes (p
Conclusions This study has demonstrated the safety and tolerability of the live biotherapeutic MRx0518 in treatment naïve cancer patients. Exploratory analyses of post-treatment samples has echoed preclinical observations of increased infiltration of immune cells following treatment and will undergo further validation. Part B will focus on investigating efficacy in a further 100 treatment naïve patients with a placebo-controlled arm.
Trial Registration NCT03934827
Ethics Approval The study was approved by East of England - Cambridge East Research Ethics Committee approval number 18/EE/0091
Date Issued
2020-12-10
Date Acceptance
2020-12-01
Citation
Journal for ImmunoTherapy of Cancer, 2020, 8 (Suppl 3), pp.A481-A482
ISSN
2051-1426
Publisher
BioMed Central
Start Page
A481
End Page
A482
Journal / Book Title
Journal for ImmunoTherapy of Cancer
Volume
8
Issue
Suppl 3
Copyright Statement
© 2020 The Author(s). This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
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Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
4D Pharma Plc
Ovarian Cancer Action
Identifier
https://jitc.bmj.com/content/8/Suppl_3/A481.2
Grant Number
RDB01 79560
NIHR-RP-011-053
C/35/2017
n/a
Publication Status
Published
Date Publish Online
2020-12-10