CD24Fc With Ipilimumab and Nivolumab to Decrease irAE (CINDI)

Inclusion Criteria 1. Male or female ≥18 years old. 2. Patients with histologically confirmed unresectable Stage III or Stage IV metastatic melanoma who have not been previously treated with a CD24Fc, anti-CTLA4 and anti-PD1/PDL1 inhibitors with documented progression. 3. Measurable disease per RECIST v1.1 criteria using imaging scans, or peripheral lesions that can be adequately documented with a picture and a ruler even if they do not meet RECIST criteria. 4. Patients must have lesion accessible for sequential biopsy (core needle biopsy or excision preferred, fine needle aspiration not eligible). 5. ECOG performance status 0 or 1. 6. Women of child-bearing potential must have a negative serum pregnancy test within 24 hour of initiation of dosing and must agree to use an effective form of contraception during the study from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Fertile men must also agree to use an effective method of birth control while on study drug and up to 6 months after the last dose of study drug. 7. Patients must have fully recovered from the effects of any major surgery or significant traumatic injury within 14 days of C1D1. 8. Adequate hematologic, hepatic, and renal function, as defined below: * Absolute neutrophil count ≥1 X 109/L, * Hgb \> 8 g/dL * Platelet count ≥ 75 X 109/L, * AST/ALT/bilirubin ≤3X ULN (patients with Gilbert syndrome can have higher bilirubin levels). * Creatinine ≤ 3 X ULN or calculated CrCl \> 30 mL/min using Cockcroft- Gault formula. 9. Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements. Exclusion Criteria 1. Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor. 2. Investigational drug use within 28 days of C1D1. 3. Chemotherapy, targeted therapy, growth factors or radiation therapy within 14 days of C1D1. 4. Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to C1D1. 5. Patients with known active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without clinical evidence of disease progression in the brain. 6. Has received a live vaccine within 28 days prior to C1D1. 7. A known active and clinically significant bacterial, fungal, or viral infection. 8. 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.