A study on patients with melanoma who are receiving cancer immunotherapy to identify specific features related to the immune system and gut bacteria that may indicate a higher risk of negative side effects from a type of cancer treatment called checkpoint inhibitors, comparing patients who experience immune-related side effects to those who do not

Not Applicable

Conditions: Detection of immunological & microbiome features consistent with toxicity in patients with melanoma treated with checkpoint inhibitor drugs.
Cancer

Registration Number: ISRCTN43419676

Lead Sponsor: ewcastle upon Tyne Hospitals NHS Foundation Trust

Brief Summary: 2024 Protocol article in https://doi.org/10.1186/s12885-024-12468-3 (added 17/06/2024)

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 80

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

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.

Study & Design

Study Type: Observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
1. Baseline microbiome diversity as measured by whole genome sequencing between irAE and non-irAE groups at a single time point<br>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.