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 relatedprocedures

• Adults ≥ 18 years of age

• Patient has histologically or radiographically confirmed HCC. Initial HCC diagnosisduring study screening can also be made based on characteristic imaging pattern perthe 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-enhancedmultiphase CT or MRI are considered radiological hallmarks of HCC given highspecificity and positive predictive value in lesions ≥1 cm in size."

• Unresectable HCC or not eligible for surgical resection or liver transplantation atthe 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 secondsabove control

• Total bilirubin level of ≤ 2.0 mg/dL

• Subjects of childbearing potential (SOCBP) must be using an adequate method ofcontraception to avoid pregnancy throughout the study and for at least 12 weeksafter the last dose of study drug to minimize the risk of pregnancy. Prior to studyenrollment, subjects of childbearing potential must be advised of the importance ofavoiding pregnancy during trial participation and the potential risk factors for anunintentional pregnancy.

• Subjects with partners of child-bearing potential must agree to usephysician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)throughout the study and should avoid conceiving children for 12 weeks following thelast dose of study drug.

Exclusion Criteria:

• Patient has been treated for this malignancy, has another active malignancy, or hashad 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 HCCwhere HCC is not the majority histology.

• Patients who experienced recent GI bleeding or intracranial bleeding or stroke inlast 12 weeks, or with uncontrolled blood pressure of history of organ rupture orperforation in last 12 weeks.

• Prior liver transplantation.

• Subjects of childbearing potential who are unwilling or unable to use an acceptablemethod to avoid pregnancy for the entire study period and for at least 12 weeksafter 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 conditionthat contraindicates the use of protocol therapy or that might affect theinterpretation of the results of the study or that puts the subject at high risk fortreatment complications, in the opinion of the treating physician.

• Administration of a vaccine containing live virus within 30 days prior to the firstdose of trial treatment. Note: Most flu vaccines are killed viruses, with theexception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus andtherefore prohibited for 30 days prior to first dose. Non-live versions of the COVIDvaccine are allowed.

• Prisoners or subjects who are involuntarily incarcerated, or subjects who arecompulsorily detained for treatment of either a psychiatric or physical illness

• Use of immunosuppressive drugs, such as steroids, and any herbs, which cannot bediscontinued prior to study entry