Safety and Efficacy of TareSphere in Patients With Unresectable Hepatocellular Carcinoma

Prior treatment

• With the extrahepatic metastasis or concurrent malignant tumors other than liver cancer;
• With diseases have not been controlled despite aggressive treatment, and which may affect the safety or the efficacy of the investigational drug in the judgement of investigators;
• Have received radiotherapy or transcatheter arterial chemoembolization (participants who have received transcatheter arterial non-iodized oil chemoembolization are judged by investigators);
• 99mTc-MAA arterial perfusion imaging shows that the single lung radiation absorbed dose \> 30 Gy;
• Received antitumor therapy or participated in other interventional clinical trials within 30 days prior to dosing;
• Have persistent, unrelieved toxicity reaction of CTCAE≥2 grade caused by previous antitumor treatment (excluding alopecia) judged by investigators;

Other illness

• Allergy to contrast agents or anesthetics;
• With the clinical manifestations of decompensated liver cirrhosis (moderate or severe ascites, upper gastrointestinal bleeding, hepatic encephalopathy, etc.);
• Active or severely infected participants requiring systemic therapy;
• With positive results of HIV antibody test;

Lab values

• Technetium (99mTc)-macroaggregated albumin (MAA) hepatic arterial perfusion imaging estimates that the NRT6003 injection cannot cover all lesions within the liver (excluding lesions previously treated by the investigator as non-active or non-progressive);

Other

• With the hepatic tumor thrombus (excluding the thrombus limited to liver segments or lobes);
• With hepatic artery malformation and unable to intubate hepatic artery;
• Severe pulmonary dysfunction (forced expiratory volume in one second, FEV1/FVC \< 50 percent or forced expiratory volume in one second (FEV1) \< 50 percent of predicted value, or maximum voluntary ventilation (MVV) \< 50 L/min);
• Estimated survival period \< 3 months;
• Hepatic artery angiography and 99mTc-MAA hepatic artery perfusion imaging demonstrate gastrointestinal shunts, which may not be remedied through vascular intervention techniques;
• Pregnant or lactating women;
• Any other reason that the investigator deems the participant unsuitable for participating in this trial.

• Aged 18 to 80 and signed informed consent;
• Diagnosed as hepatocellular carcinoma clinically, by imaging and/or pathology based on the guideline of the National Health Commission of the People's Republic of China (2022);
• Evaluated by the investigator as not suitable for surgical resection/ablation, or there are other reasons unsuitable for surgical resection/ablation, or the participant refuses surgical resection/ablation;
• At least one well defined tumor (mRECIST), assessed by enhanced MRI or CT images;
• Child-Pugh score ≤ 7;
• Eastern Cooperative Oncology Group performance status ≤ 1;
• Tumor burden ≤ 50 percent of the total liver volume;
• Adequate organ function: (1) Blood routine \[no blood transfusion or granulocyte colony-stimulating factor (G-CSF) treatment within 14 days\]: absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; platelet (PLT) ≥ 80 × 10\^9/L; hemoglobin (HGB) ≥ 90 g/L; (2) Liver function: total bilirubin (TBIL) ≤ 2 times upper limit of normal (ULN); alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5. 0×ULN; Albumin \> 30 g/L; (3) Renal function: Creatinine (Cr) ≤ 1.5×ULN; creatinine clearance rate (CCr)≥ 50 mL/min (calculated according to Cockcroft-Gault formula); (4) Coagulation function: international normalized ratio (INR), prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN \[If any participant takes warfarin or heparin for anticoagulation therapy, the investigator should evaluate whether the participant meet the requirements of the protocol\]; (5) Cardiovascular function: left ventricular ejection fraction (LVEF) ≥ 50 percent assessed by ultrasonic cardiogram;
• Women and men of childbearing age must agree to take strict and effective contraceptive measures during the study period and within 6 months after the end of the trial. Men are forbidden to donate sperm. The pregnancy test results of female participants of childbearing age during the screening period and within 24 hours before administration must be negative.