Study of NP-101 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Undergoing Y-90 Treatment

Inclusion Criteria: * Must provide written informed consent prior to initiating any trial related procedures * Adults ≥ 18 years of age * Patient has histologically or radiographically confirmed HCC. Initial HCC diagnosis during study screening can also be made based on characteristic imaging pattern per the AASLD (American Association for the Study of Liver Diseases) guidelines (https://journals.lww.com/hep/fulltext/2023/12000/aasld\_practice\_guidance\_on\_prevention,\_diagnosis,.27.aspx). Per AASLD guidelines: "arterial phase hyperenhancement (APHE) and washout on portal venous or delayed phases of contrast-enhanced multiphase CT or MRI are considered radiological hallmarks of HCC given high specificity and positive predictive value in lesions ≥1 cm in size." * Unresectable HCC or not eligible for surgical resection or liver transplantation at the time of screening. * At least one untreated target lesion that could be measured in one dimension, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). * Must have a Child-Turcotte-Pugh score of Class A (5-6) or B7 * ECOG of 0 or 1 * Adequate hematologic, renal, and coagulation function, as evidenced by: * Hemoglobin ≥ 9 g/dL * Absolute neutrophil count ≥ 1,500/mm3 * Platelet count ≥ 75,000/mm3 * Creatinine clearance ≥ 30 mL/min * International Normalized Ratio (INR) ≤ 1.5 or prothrombin time ≤ 3 seconds above control * Total bilirubin level of ≤ 2.0 mg/dL * Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 12 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. * Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 12 weeks following the last dose of study drug. Exclusion Criteria: * Patient has been treated for this malignancy, has another active malignancy, or has had an active malignancy within the last two years. * Previous treatment with Y90 radioembolization or systemic treatment for HCC. * Evidence of macrovascular invasion or extrahepatic metastases. * Patient has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC where HCC is not the majority histology. * Patients who experienced recent GI bleeding or intracranial bleeding or stroke in last 12 weeks, or with uncontrolled blood pressure of history of organ rupture or perforation in last 12 weeks. * Prior liver transplantation. * Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 12 weeks after the last dose of study drug. * Subjects who are confirmed to be pregnant or breastfeeding. * History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician. * Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose. Non-live versions of the COVID vaccine are allowed. * Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness * Use of immunosuppressive drugs, such as steroids, and any herbs, which cannot be discontinued prior to study entry