CD24Fc for the Treatment of Immune Related Adverse Events in Patients with Advanced Solid Tumors, TIRAEC Study

Inclusion Criteria

• Ability to understand and willingness to sign an informed consent form
• Histologically confirmed advanced solid tumors
• Patients must have grade 2 or 3 irAEs from at least one ICI-containing regimen. Both newly emerging and persistent irAEs are allowed. Systemic steroid therapy or any other form of immunosuppressive therapy for irAEs is allowed. The specific irAEs are * Grade 2-3 diarrhea/colitis: Patients with >= 4 stools per day or moderate-severe increase in ostomy output compared to baseline but not life-threatening diarrhea * Grade 2-3 pneumonitis: Mild to moderate (grade 2) or severe (grade 3) symptoms (including hypoxia, shortness of breath, requiring oxygen) but not life-threatening respiratory compromise requiring urgent intervention (e.g., tracheostomy or intubation) * Grade 2-3 renal irAE: Creatine increased between 1.6-6.0 x upper limit of normal (ULN) or =< 3.0 x baseline if baseline was abnormal, estimated glomerular filtration rate (eGFR) or creatinine clearance >= 15 ml/min/1.73m^2 but not life-threatening consequences or requiring dialysis * Grade 2-3 hepatic irAE: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) levels 3-20 x ULN if baseline was normal or 2-20 x baseline if baseline was abnormal, T bilirubin increased =< 10.0 x ULN if baseline was normal or =< 10 x baseline if baseline was abnormal * Grade 2-3 skin rash: moderate (10-30% body surface area, BSA) to severe (> 30% BSA) but not life-threatening skin lesions or Stevens-Johnson syndrome
• Eastern Cooperative Oncology Group (ECOG) performance status < 2
• Life expectancy of >= 3 months at the time of enrollment
• Pretreatment absolute neutrophil count (ANC) >= 1,000/uL obtained within 14 days prior to 1st dose of treatment
• Pretreatment hemoglobin >= 8 gm/dL obtained within 14 days prior to 1st dose of treatment
• Pretreatment platelet count of >= 75,000/uL obtained within 14 days prior to 1st dose of treatment
• Female subjects who are of non-reproductive potential (i.e., post-menopausal by history – no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Or, female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration
• Male and female subjects who agree to use highly effective method of birth control (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices [IUDs], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug

Exclusion Criteria

• Prior CD24Fc therapy
• Any known active hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, including patients who have an active infection requiring systemic therapy. History of COVID-19 or known asymptomatic carrier of SARS-CoV-2 virus is allowed
• Pregnant or lactating women
• Any medical condition including additional laboratory abnormalities, or psychiatric illness that would, in the opinion of the investigator, prevent the subject from participating and adhering to study related procedures
• Any known severe bacterial, fungal, or viral infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 2 weeks prior to enrollment
• Patients with concomitant proarrhythmic medications
• Patients with heart failure in New York (NY) Heart Association stage IV
• Any grade 4 irAE symptoms and Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 grade 4 toxicity
• AST, ALT, gamma glutamyl transpeptidase (GGT), or ALP > 20.0 x ULN regardless of baseline
• Blood bilirubin > 10.0 x ULN regardless of baseline
• Creatinine > 6.0 x ULN
• Urine: Anuria < 140 ml in 24 hours
• Electrolytes hyponatremia, sodium < 120 mmol/L
• Hypokalemia, potassium < 2.5 mmol/L
• Creatine kinase (CPK) > 10.0 ULN
• Electrocardiogram (ECG): Prolonged QT interval >= 480 mS, corrected by Fridericia’s formula. Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrythmia