The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy.
Authors
Thompson, Nicola A
Robinson, Matthew J
Neville, B Anne
Vervier, Kevin
Harris, Simon R
Adams, David J
Dalchau, Katy
Bruce, David
Demiris, Nikolaos
Lawley, Trevor D
Publication Date
2022-01-24Journal Title
BMC Cancer
ISSN
1471-2407
Publisher
Springer Science and Business Media LLC
Volume
22
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Thompson, N. A., Stewart, G., Welsh, S., Doherty, G., Robinson, M. J., Neville, B. A., Vervier, K., et al. (2022). The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy.. BMC Cancer, 22 (1) https://doi.org/10.1186/s12885-021-09156-x
Abstract
BACKGROUND: The gut microbiome is implicated as a marker of response to immune checkpoint inhibitors (ICI) based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early studies suggest faecal microbial transfer may have therapeutic potential, converting ICI non-responders into responders. So far, identification of specific responsible bacterial taxa has been inconsistent, which limits future application. The MITRE study will explore and validate a microbiome signature in a larger scale prospective study across several different cancer types. METHODS: Melanoma, renal cancer and non-small cell lung cancer patients who are planned to receive standard immune checkpoint inhibitors are being recruited to the MITRE study. Longitudinal stool samples are collected prior to treatment, then at 6 weeks, 3, 6 and 12 months during treatment, or at disease progression/recurrence (whichever is sooner), as well as after a severe (≥grade 3 CTCAE v5.0) immune-related adverse event. Additionally, whole blood, plasma, buffy coat, RNA and peripheral blood mononuclear cells (PBMCs) is collected at similar time points and will be used for exploratory analyses. Archival tumour tissue, tumour biopsies at progression/relapse, as well as any biopsies from body organs collected after a severe toxicity are collected. The primary outcome measure is the ability of the microbiome signature to predict 1 year progression-free survival (PFS) in patients with advanced disease. Secondary outcomes include microbiome correlations with toxicity and other efficacy end-points. Biosamples will be used to explore immunological and genomic correlates. A sub-study will evaluate both COVID-19 antigen and antibody associations with the microbiome. DISCUSSION: There is an urgent need to identify biomarkers that are predictive of treatment response, resistance and toxicity to immunotherapy. The data generated from this study will both help inform patient selection for these drugs and provide information that may allow therapeutic manipulation of the microbiome to improve future patient outcomes. TRIAL REGISTRATION: NCT04107168 , ClinicalTrials.gov, registered 09/27/2019. Protocol V3.2 (16/04/2021).
Keywords
Study Protocol, Microbiome and Cancer, Microbiome, Immunotherapy, Melanoma, Renal cancer, Non-small cell lung cancer, Biomarker, Immune checkpoint inhibitor, Efficacy, Toxicity
Sponsorship
Cancer Research UK (C96/A25177)
MRC (MR/T024097/1)
Identifiers
s12885-021-09156-x, 9156
External DOI: https://doi.org/10.1186/s12885-021-09156-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333300
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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