Inclusion Criteria:

1. Diagnosis of HCC:

   • For patients without underlying cirrhosis, diagnosis of HCC documented by cytology and/or histology
   • For patients with underlying cirrhosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Appendix V).
2. HCC is advanced, refractory, or metastatic, and no standard therapies are expected to be curative.
3. At least 18 years of age.
4. For subjects in the dose-confirmation (RP2D) phase only: Measurable disease, using Response Evaluation Criteria in Solid Tumors (RECIST, Appendix IV). (Note that a lesion that has been subjected to radiotherapy or chemoembolization cannot be used as a target lesion.)
5. Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at baseline.

6. The following laboratory values must be documented within 3 days prior to initiation of study drug:

   • Absolute neutrophil count (ANC) greater than or equal to 1 x 109/L
   • Platelet count greater than or equal to 50 x 109/L
   • Serum creatinine less than or equal to 2.0 mg/dL
   • Aspartic aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal.
   • Total bilirubin ≤ 3.0 mg/dL.
   • Serum albumin ≥ 3.0 g/dL.
   • International normalized ratio (INR) ≤ 2.3.
7. Esophageal bleeding and varices, if present, have been sclerosed or banded, and no bleeding episodes have occurred during the prior 6 months.
8. Life expectancy of ≥ 12 weeks.
9. For women of childbearing potential, negative serum pregnancy test result.
10. Absence of active malignancy other than HCC within 2 years of entry, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
11. Provide written informed consent to participate.

12. Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study related procedures.

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Exclusion Criteria:

1. Any chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, corticosteroids > 20 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
2. Major surgery or radiation therapy within 28 days prior to initiation of study drug.
3. Severe liver dysfunction (Child-Pugh Class C or hepatic encephalopathy).
4. Active infection requiring systemic therapy.
5. Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
6. History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 450 msec for males or > 470 msec for females.
7. Pregnant or lactating female.
8. Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the Principal Investigator (PI), are effective and adequate for that patient's circumstances while on study drug.
9. Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug.
10. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness.

11. Any severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the patient inappropriate for entry into this study.

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