Abatacept in Immune Checkpoint Inhibitor Myocarditis

Inclusion Criteria:

1. Must have provided informed consent in a manner approved by the Investigator'sInstitutional Review Board (IRB) prior to any study-related procedure beingperformed. If a participant is unable to provide informed consent due to his/hermedical condition, the participant's legally authorized representative may consenton behalf of the study participant, as permitted by local law and institutionalStandard Operating Procedures;

2. Aged greater than or equal to 18 years at the time of informed consent;

3. Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined asadministered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis),alone or in combination with other cancer therapies (i.e. chemotherapy, radiationtherapy or targeted therapy). The FDA-approved ICI could be given as part of aclinical trial but not in combination with a new investigational agent which maycause myocarditis;

4. A diagnosis of myocarditis.

5. Hospitalized at the time of randomization;

6. On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000mg of solumedrol per day for myocarditis within 24 hours of first administration ofstudy drug;

7. Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardialinjury will be defined as an institutional troponin (either conventional orhigh-sensitivity troponin I or T, using the standard institutional assay) with avalue that is ≥5 times the upper limit of the reference standard normal for thatinstitution. The troponin assay may be adjusted based on sex depending oninstitutional standards. This value of troponin of ≥5 times above the institutionalupper limits of normal value must be noted within 10 days prior to potentialrandomization. The 10-day period can be in the outpatient or inpatient setting. Forexample, a participant with a troponin value that on one occasion was ≥5 times theupper limits of institutional normal in the 10-day window prior to potentialrandomization (whether in the inpatient or outpatient setting), but later decreasesbelow that threshold, typically due to starting corticosteroids, would still beconsidered eligible;

8. The following laboratory parameters, not older than 48 hours at the time ofrandomization, and measured as part of usual care:

• Total white blood cell (WBC) count >2,500/μl

• Absolute neutrophil count (ANC) >1,500/μL

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 timesthe upper limit of the institutional normal ranges;

9. Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized)must have a negative highly sensitive urine or serum pregnancy test prior torandomization. Participating women of childbearing potential must be willing toconsistently use effective methods of contraception from screening until at least 90days after administration of the last dose of study drug. Participating men mustalso be willing to consistently use effective methods of contraception fromscreening until at least 90 days after administration of the last dose of studydrug; and

10. Must be willing and able to abide by all study requirements and restrictions.

Exclusion Criteria:

1. Must not have experienced any of the following (as defined in the section on theprimary endpoint) in the 30-day period prior to randomization:

• A sudden cardiac arrest

• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type IIsecond degree atrioventricular block or third degree (complete)atrio-ventricular (AV) block, for which an intervention with a temporary orpermanent pacemaker is completed or recommended).

• A significant tachyarrhythmia (ventricular fibrillation of any duration orsustained ventricular tachycardia (>30 seconds, >120 beats per minute); or aventricular tachyarrhythmia requiring intervention.

2. Recent (≤2 month) exposure to abatacept or belatacept.

3. Concurrent or recent (≤2 month) use of the following non-corticosteroidimmunosuppressive therapies prior to randomization: mycophenolate, JAK STATinhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, andfilgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, andplasma exchange. The use of intravenous immunoglobulin is permitted prior torandomization and during study treatment.

4. Currently enrolled in another interventional study utilizing systemic agents for themanagement of ICI-related toxicities.

5. Female who is pregnant, breastfeeding, or is considering becoming pregnant duringthe study or for approximately 90 days after the last dose of study drug.

6. Male who is considering fathering a child or donating sperm during the study or forapproximately 30 days after the last dose of study drug.

7. Any active, chronic, or recurrent viral infection that, based on the investigator'sclinical assessment, makes the participant an unsuitable candidate for the study.These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent ordisseminated (even a single episode) herpes zoster, and disseminated (even a singleepisode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surfaceantigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleicacid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B coreantibody (HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA)detectable in any participant with anti-HCV antibody (HCV Ab). Patients with activeCovid-19 infection will be excluded. This is defined as the period of ongoingsymptoms in the setting of a positive Covid-19 test, or until 10 days after symptomonset and after resolution of fever for at least 24 hours, without the use offever-reducing medications.

8. Known active tuberculosis (TB), history of incompletely treated TB, suspected orknown extrapulmonary TB, suspected or known systemic bacterial or fungal infections;

9. Receipt of any live vaccine within four weeks prior to the first dose of study drug,or expected need of live vaccination during study participation including at least 90 days after the last dose of IV study drug.

10. Any medical condition that could interfere with, or for which the treatment mightinterfere with, the conduct of the study or interpretation of the study results, orthat would, in the opinion of the Investigator, increase the risk of the participantby participating in the study.

11. Any factors that, in the Investigator's opinion, are likely to interfere with studyprocedures, such as history of noncompliance with scheduled appointments.