Infliximab for the Treatment of Checkpoint Inhibitor Associated Diabetes Mellitus

Inclusion Criteria

• Patients on ICI referred to endocrine for new diagnosis of CIADM, will be included provided they are within 12 months of last dose of ICI and if they have: * New onset diabetes ≥ 200 mg/dl and/or A1c ≥ 6.5 OR * Worsening glycemic control: requiring insulin per clinician assessment (fasting glucose or average glucose on continuous glucose monitoring [CGM] > 20% and/or A1c > 0.5% from prior to ICI use ) AND/OR * If Presenting with diabetic ketoacidosis (DKA)/hyperosmolar hyperglycemic state (HHS): include if within 6 weeks of presentation AND * Must have detectable random c-peptide level 0.2-1 ng/mL with blood glucose of 145 mg/dl
• Age ≥ 18 years. Because adverse event data are currently available on the use of infliximab in combination with in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN
• Creatinine ≤ institutional ULN
• Cardiac ejection fraction > 50%
• Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of infliximab administration
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients already on insulin for pre-existing type 1 or type 2 diabetes
• Patients with undetectable c-peptide levels i.e. < 0.2 with blood glucose of 145 mg/dl or higher
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a history of (h/o) active tuberculosis (TB) or latent TB will be excluded
• Patients with known history of any New York Heart Association (NYHA) class heart failure or ejection fraction < 50% will be excluded
• Patients requiring supraphysiological doses of steroids i.e. prednisone > 10mg of equivalent at the time of study entry, will be excluded
• Patients who have ICI hepatitis and myocarditis will be excluded
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities ≥ grade 2) with the exception of alopecia
• Patients who are receiving any other investigational agents for CIADM
• History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to infliximab or other agents used in study
• Required: any concomitant drugs used will be excluded
• Patients with uncontrolled intercurrent illness: active infection/ sepsis
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and breastfeeding women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with infliximab. Breastfeeding should be discontinued if the mother is treated with infliximab. These potential risks may also apply to other agents used in this study