Genetic Determinants of Myocarditis Induced by Immune-checkpoint Inhibitors

Recruiting now

Conditions studied: ICI-myocarditis

In brief

Immune checkpoint inhibitors (ICI) are active in multiple cancers. Their main drawback is the incidence of immune related adverse events; among which ICI-myocarditis (ICIM) is rare but can be the most life-threatening (up to 50% lethal). ICIM is due to ICI unleashing cytotoxic auto-reactive T-cells recognizing a culprit target antigen located on muscles and destroying them. Most often, ICIM occurs within a systemic ICI-myotoxicity, with peripheral muscular involvement (ICI-myositis), mimicking eventually myasthenia-gravis syndrome. Human Leukocyte Antigen (HLA) are cell surface proteins key for the regulation of the immune system acting via presentation of culprit antigens by antigen presenting cells (macrophages) to T-cells, subsequently triggering the destruction/tolerance of cells carrying this antigen. The HLA system (chromosome 6) is the most polymorphic region in the human genome and is associated with auto-immunity including myocarditis. HLA class I alleles have been strongly associated with some T-cell-mediated drug hypersensitivity reactions with handful patients needed to be tested to prevent a single case, leading to globally required cost-effective HLA typing pre-prescription for some drugs.

Key facts

Study ID

NCT06734689

Run by

Assistance Publique - Hôpitaux de Paris

People needed

500

Starts

2025-09-23

Expected to finish

2028-07-20

Last updated by the study team

2025-11-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Cancer patients on ICI since at least 3 months with a minimum of 2 ICI doses received having no appearance (as compared to baseline known pre-ICI) of a new cardio-muscular symptoms or ECG abnormality or WMA or troponin-T increase (above ULN if normal prior to ICI start, or over twice its troponin-T baseline value if abnormal before ICI start).
• Signature of informed consent before any trial procedure from the patient
• Patients covered by social security regimen (excepting AME).

You may not qualify if…

• Age <18 years of age.
• Pregnant or breast-feeding women
• People under legal protection measure (safeguard measures)
• Specific exclusion criteria for the magnetic resonance imaging sub-study (MRI)
• Patients with a contraindication to MRI (claustrophobia, some wearing equipment with magnetic properties: pacemaker, ferromagnetic equipment, etc.)
• Intolerance to gadolinium, or severe renal insufficiency (GFR<30 ml/min/1.73 m2).
• Of note, the other groups of patients needed to complete this study; i.e the patients with refuted suspicion of ICI-myocarditis who will serve as controls, and the patients with ICI-myocarditis (cases) are included in another protocol (NCT05454527)

Where it is running

• Hôpital Pitié Salpêtrière — Paris, France (enrolling)

Full record on ClinicalTrials.gov

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