NCT04107168

Microbiome Immunotherapy Toxicity and Response Evaluation

An Observational Study to Evaluate the Microbiome as a Biomarker of Efficacy and Toxicity in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 1,800 (estimated)
• Sponsor: CCTU- Cancer Theme · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This is a observational study to investigate how the microbiome correlates with efficacy and toxicity of immune checkpoint inhibitors in patients with advanced cancer.

Detailed description

The gastrointestinal microbiome of a healthy individual is comprised of many hundreds of bacteria species and thousands of bacteria strains. The composition of bacteria in an individual's microbiome can change over time and this can be influenced by factors including diet, drugs, genetics and infection. These bacteria play a central role in digestion of food, development and regulation of our immune system as well as our resistance to pathogens. Recent evidence suggest that a patient's intestinal microbiota composition plays a critical, though as yet poorly defined, role in determining both therapeutic efficacy and likelihood of significant adverse events to T-cell checkpoint inhibitor immunotherapy. Immune checkpoint inhibitors are revolutionising treatment of many types of metastatic cancer, including melanoma, renal and non-small cell lung cancer, in the expectation of improving patient overall survival. However, they have limitations as they do not work for all patients and can cause unpredictable, complex immune-related toxicities. The investigators will perform a detailed study of cancer patients receiving checkpoint inhibitors. Saliva and a series of stool samples will be collected from each patient to analyse their microbiome and will be linked to treatment response, by examining blood samples and - if available - tumour and organ samples. The investigators hope this work will enable personalisation of patient immunotherapies based on microbiome biomarkers, as well as precisely manipulate a patient's microbiota to optimise their immunotherapy. In addition, participants who have consented to take part in an optional sub-study may be offered a single nasopharyngeal swab for COVID-19 antigen before study entry. The investigators hope that that this identify correlations between the microbiome and COVID-19. Comparison with a limited cohort of healthy household members (up to 360 volunteers) acting as controls will provide additional essential information about the role of the patient-specific microbiome.

Conditions

• Melanoma
• Renal Cancer
• Lung Cancer

Interventions

Type	Name	Description
DRUG	Nivolumab	A human immunoglobulin G4 (IgG4) monoclonal antibody, which binds to the programmed death-1 receptor (PD-1).
DRUG	Pembrolizumab	A human immunoglobulin G4-kappa (IgG4-kappa) monoclonal antibody that targets PD-1.
DRUG	Ipilimumab	A human immunoglobulin G1 (IgG1) monoclonal antibody raised against cytotoxic T lymphocyte antigen-4 (CTLA-4).
DRUG	Durvalumab	A human immunoglobulin G1-kappa (IgG1-kappa) monoclonal antibody that binds to programmed death ligand 1 (PD-L1).
DRUG	Tremelimumab	A fully human monoclonal antibody raised to target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
DRUG	Atezolizumab	A humanised IgG1 monoclonal antibody raised to target programmed death-ligand 1 (PD-L1).
DRUG	Bevacizumab	A humanised IgG1 monoclonal antibody raised to target vascular endothelial growth factor (VEGF).

Timeline

• Start date: 2020-07-08
• Primary completion: 2024-07-08
• Completion: 2025-07-08
• First posted: 2019-09-27
• Last updated: 2023-02-16

Locations

13 sites across 1 country: United Kingdom