This is a phase Ib/II clinical trial to test safety and efficacy of combining CD24Fc with
ipilimumab and nivolumab to decrease irAE, with built-in interim analyses, and safety and
response stopping rules.
This is a phase 1b/II clinical trial using a fixed recommended phase 2 dose (RP2D) of CD24Fc
to explore the safety and efficacy of combining CD24Fc with ipilimumab and nivolumab to
reduce the toxicity of immunotherapy combination, in patients who are naïve to anti-PD1/L1
based checkpoint inhibitors. The dosing of nivolumab and ipilimumab will be fixed at FDA
approved levels for each indication. Dosing of the drugs will continue until disease
progression, unacceptable toxicity, or any other discontinuation criterion is met. Patients
who complete 12 months on study treatment and demonstrate clinical benefit with manageable
toxicity will be given the opportunity to continue treatment for another 12 months upon
agreement between investigator and drug manufacturers.
1. Male or female ≥18 years old.
2. Patients with histologically confirmed unresectable Stage III or Stage IV metastatic
melanoma, renal cell carcinoma, or MSI-high or dMMR colorectal carcinoma, who have not
been previously treated with a CD24Fc, anti-CTLA4 and anti-PD1/PDL1 inhibitors with
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
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
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
- Creatinine ≤ 3 X ULN or calculated CrCl > 30 mL/min using Cockcroft- Gault
9. Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements.
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
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.