Imperial College London
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DrJonathanKrell

Faculty of Medicine, Department of Surgery & Cancer

Clinical SL in Medical Oncology (Gynaecological Oncology)
 
 
 
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j.krell

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lythgoe:2020:10.1136/jitc-2020-sitc2020.0805,
author = {Lythgoe, M and Stebbing, J and Pickford, E and Glasmacher, A and Adriani, M and Fyvie, G and Frampton, A and Stevenson, A and Krell, J},
doi = {10.1136/jitc-2020-sitc2020.0805},
journal = {Journal for ImmunoTherapy of Cancer},
pages = {A481--A482},
title = {805Safety and emerging evidence of immune modulation of the live biotherapeutic MRx0518 in the neoadjuvant setting for patients awaiting surgical removal of solid tumours},
url = {http://dx.doi.org/10.1136/jitc-2020-sitc2020.0805},
volume = {8},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 pan
AU  - Lythgoe,M
AU  - Stebbing,J
AU  - Pickford,E
AU  - Glasmacher,A
AU  - Adriani,M
AU  - Fyvie,G
AU  - Frampton,A
AU  - Stevenson,A
AU  - Krell,J
DO  - 10.1136/jitc-2020-sitc2020.0805
EP  - 482
PY  - 2020///
SN  - 2051-1426
SP  - 481
TI  - 805Safety and emerging evidence of immune modulation of the live biotherapeutic MRx0518 in the neoadjuvant setting for patients awaiting surgical removal of solid tumours
T2  - Journal for ImmunoTherapy of Cancer
UR  - http://dx.doi.org/10.1136/jitc-2020-sitc2020.0805
UR  - https://jitc.bmj.com/content/8/Suppl_3/A481.2
UR  - http://hdl.handle.net/10044/1/85139
VL  - 8
ER  -
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