AbataCept for the Treatment of Immune-cHeckpoint Inhibitors Induced mYocarditiS

A vizsgálat adatai

Ki végzi

Assistance Publique - Hôpitaux de Paris

Azonosító

NCT05195645

A regiszteradat frissítve

2026. július 16.

Eredeti leírás

Immune-checkpoint-inhibitors (ICI) have revolutionized treatment for about 20 cancer types. They unleash anti-tumor immune responses. Unfortunately, in 0.36-1.23% of patients, this activation can also lead to lethal immune-related adverse events (irAEs) that can affect any organ. Among those irAEs, ICI-induced myocarditis was the most frequently fatal with death rate reaching 50% in a large case-series of over 100 patients.A teljes eredeti leírásKevesebb

Immune-checkpoint-inhibitors (ICI) have revolutionized treatment for about 20 cancer types. They unleash anti-tumor immune responses. Unfortunately, in 0.36-1.23% of patients, this activation can also lead to lethal immune-related adverse events (irAEs) that can affect any organ. Among those irAEs, ICI-induced myocarditis was the most frequently fatal with death rate reaching 50% in a large case-series of over 100 patients.

This study is a dose-finding Phase II trial where 3 abatacept IV regimen (A-10 mg/kg; B-20 mg/kg and C-25 mg/kg at Day0, Day5+/-2, Day14+/-2) will be tested aiming at reaching promptly (after the first dose) and sustainably a CD86RO≥80% during the first 3 weeks of ICI-myocarditis management. The main objective is to find the lowest dose required to achieve a circulating monocytes CD86RO≥80% within the first week of treatment and sustainably over three weeks. The target population is all adult patients with cancer (all cancer types) treated by immune checkpoint inhibitors (anti-PD1, anti-PDL1, anti-CTLA4 monotherapies or combination) and presenting drug-induced myocarditis.

Bevonási feltételek: Age ≥ 18 years old; Weight ≥ 40 kg and ≤ 125 kg; Patients treated with ICI immunotherapy (monotherapy or combination), including anti-PD1, anti-PDL1, anti-CTLA4; and including any type of cancer (even those in which ICI is not currently approved by regulatory); Definite, probable or possible ICI-induced myocarditis according to the diagnostic criteria of the most recent expert consensus recommendations (e.g27, to be updated with any new recommendations to be published); Severe or corticosteroid-resistant ICI-myocarditis:; Severe ICI-myocarditis is defined either 1/ by the appearance of an alteration of the LVEF<50% or a wall motion kinetics abnormality, or 2/ by the appearance of ventricular tachycardias or high-grade conductive disorders (atrioventricular block grade 2 or 3) or 3/ by the association with myasthenia gravis-like-syndrome (diplopia, ptosis, diaphragmatic dysfunction, dysarthria, dysphonia, dysphagia) or 4/ by troponin-T levels above 32 times the upper limit of the normal (a population at very high-risk ~75% of major cardiomuscular events in the month following initial presentation, cf. Circulation. 2023 Aug 8;148(6):473-486); Corticosteroid-resistant ICI-myocarditis is defined by the absence of decrease in troponin levels or the appearance/persistence of severity criteria despite receiving prednisone dose ≥0.5 mg/kg/day for ≥2 days; Signature of informed consent before any trial procedure from the patient or legal representative or the close relative; Patients covered by social security regimen (excepting AME); Withhold of ICI.

Kizáró feltételek: Being treated with abatacept or belatacept within 3 months prior to inclusion; Being treated with anti-thymoglobulin, or alemtuzumab within 6 weeks of the first scheduled dose of abatacept; Untreated and/or uncontrolled bacterial, fungal, or viral infection; Known hypersensitivity to abatacept or belatacept; For women of childbearing age, lack of effective contraception throughout the duration of participation in the study; Pregnancy, breast-feeding or planning to become pregnant during the study period; Patient participating to another interventional study (RIPH 1 only); People under legal protection measure (tutorship, curatorship or safeguard measures).

ClinicalTrials.gov NCT05195645