Background: Patients with myocarditis secondary to treatment with an immune checkpoint inhibitor (ICI) represent a poor prognosis population with a critical unmet clinical need. Data have shown that the rate of major adverse cardiac events (MACE) with ICI myocarditis despite administration of corticosteroids ranges from 25-50%. Abatacept is a selective co-stimulation modulator that inhibits T cell activation by binding to CD80 and CD86, thereby blocking its interaction with CD28. In preclinical animal models of ICI myocarditis, the administration of abatacept led to a reduction in cardiac immune activation and an increase in survival. Methods: The abatacept for immune checkpoint inhibitor associated myocarditis (ATRIUM) trial is designed as a phase 3, investigator-initiated, randomized, placebo-controlled study to evaluate the efficacy and safety of abatacept compared to placebo in hospitalized participants with ICI associated myocarditis. Hospitalized participants diagnosed with ICI-related myocarditis, as defined by the International Cardio-Oncology Society, ≥ 18, with serum evidence of ongoing myocardial injury (troponin ≥5 times the upper limit normal), and treated, or with intent to treat, with 1000 mg of solumedrol/day are eligible. In the randomized protocol, participants receive either abatacept (10 mg/kg) or placebo given IV followed by study drug infusion/placebo again at 24 hours and on day 14. Of note, there is an optional 4th dose on day 28. The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in MACE among participants hospitalized with myocarditis secondary to an ICI. The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrhythmias, significant bradyarrhythmias, or incident heart failure. Each component of the primary composite end point will be evaluated individually as a secondary endpoint, as are troponin levels, rates of deep venous thrombosis and pulmonary embolism, and incidence rates of treatment-related adverse events. Exploratory outcomes focus on cancer outcomes, healthcare utilization, quality of life, and correlative studies. Recently, the trial has been amended to allow eligible participants who have achieved an ATRIUM primary end-point prior to randomization to be eligible for inclusion in the RESCUE arm of the protocol where they will be given open-label Abatacept on day 1, 2, 14, with optional dose at 28. The study is open at 20 sites across the US with a plan for a total of 50 locations across US and Canada. This study is recruiting at time of submission. Target enrollment is 390 patients. Clinical trial information: NCT05335928.