Detection of immunological & microbiome features consistent with toxicity in patients with melanoma treated with checkpoint inhibitor drugs. Cancer
Conditions
Interventions
MEDALLION aims to recruit up to 80 patients consented to therapy with checkpoint inhibition (CPI) in the form of either anti-PD1, anti-PDL1, anti-CTLA4 or combination of these therapies for cancer. Pa
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patient >18 years of age. 2. Confirmed diagnosis of malignant melanoma. 3. Shared decision by oncologist and patient to proceed with CPI treatment, either with the combination of ipilimumab and nivolumab, or with single-agent nivolumab or pembrolizumab as standard of care. 4. Patient is judged as being capable of understanding the information sheet and of giving informed consent according to the Mental Capacity Act 2005. 5. Written informed consent to participate in the study.
Exclusion criteria
Exclusion criteria: 1. Known pre-existing autoimmune or immune-mediated inflammatory disease requiring immunomodulatory treatment, including (but not limited to) inflammatory bowel disease (Crohn’s disease, ulcerative colitis) autoimmune endocrinopathy or hepatitis, vitiligo and inflammatory arthritis. 2. Received enteral or parenteral steroids within past month (topical, inhaled or intranasal permitted). 3. Previous treatment with CPI therapy. 4. Vaccination within the past 4 weeks, except COVID-19 vaccination permitted. 5. Known chronic infection. 6. Current pregnancy, or pregnancy planned within next 6 months 7. Inability to provide informed consent and/or undergo any of the procedures mandated by the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CD4+ T cell phospho-STAT3 measurement by flow cytometric analysis at the pre-irAE time-point compared to that seen in non-irAE patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Baseline microbiome diversity as measured by whole genome sequencing between irAE and non-irAE groups at a single time point 2. Peripheral immune cell subsets as determined by multi-parameter flow cytometry between irAE and non-irAE groups at the pre-irAE event or matched timepoint for the non-irAE group. | — |
Countries
England, United Kingdom
Contacts
Public ContactAbigail Gault
Outcome results
None listed