Hepatic Arterial Infusion Chemotherapy With Lipiodol Embolization in Advanced Hepatocellular Carcinoma

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with therequirements and restrictions listed in the informed consent form (ICF).

2. Histologically or clinically (typical HCC imaging findings by multi-phase CT or MRI)diagnosed HCC.

3. Barcelona Clinic Liver Cancer (BCLC) Stage C disease (liver confined disease orliver predominant disease, as determined by the investigator) or BCLC Stage Bdisease who failed standard treatment (i.e., TACE in intermediate stage HCC orsystemic therapy in advanced HCC) or refused standard treatment or intolerable tostandard treatment.

4. Archival tissue available (< 2 years) or agree to have biopsy tissue at baseline

5. Age > 20 years at the time of study entry.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. Child-Pugh class A or B7

8. ≥1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1in the liver

9. Body weight >30 kg

10. Adequate normal organ and marrow function as defined below:

(1) Hemoglobin ≥9.0 g/dL (2) Absolute neutrophil count (ANC) ≥1.0 x 109/L (≥ 1,000 per mm3) (3) Platelet count ≥75 x 109/L (≥75,000 per mm3) (4) Serum bilirubin ≤2 x institutional upper limit of normal (ULN). (5) AST (SGOT)/ALT (SGPT) ≤3x institutional upper limit of normal unless active liver malignancies are present, in which case it must be ≤5x ULN (6) Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: 11. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

12. Patient is willing and able to comply with the protocol for the duration of thestudy including undergoing treatment and scheduled visits and examinations includingfollow up.

13. Must have a life expectancy of at least 12 weeks

Exclusion Criteria:

1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma

2. The result of lung perfusion scan of the HAIC port > 20%

3. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of aninterventional study

4. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,endocrine therapy, targeted therapy, biologic therapy, tumor embolization,monoclonal antibodies) ≤14 days prior to the first dose of the study drug. Ifsufficient wash-out time has not occurred due to the schedule or PK properties of anagent, a longer wash-out period will be required, as agreed by the principalinvestigator.

5. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with theexception of alopecia, vitiligo, and the laboratory values defined in the inclusioncriteria.

6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormonereplacement therapy) is acceptable.

7. Major surgical procedure (as defined by the Investigator) within 28 days prior tothe first dose of study treatment.

8. Uncontrolled intercurrent illness, including but not limited to, ongoing or activeinfection (except HBV infection or HCV infection), symptomatic congestive heartfailure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia,interstitial lung disease, serious chronic gastrointestinal conditions associatedwith diarrhea, or psychiatric illness/social situations that would limit compliancewith study requirement, substantially increase risk of incurring AEs or compromisethe ability of the patient to give written informed consent

9. History of another primary malignancy except for conditions listed in the protocol.

10. History of leptomeningeal carcinomatosis

11. Brain metastases or spinal cord compression. Patients with suspected brainmetastases at screening should have an MRI (preferred) or CT each preferably with IVcontrast of the brain prior to study entry

12. History of active primary immunodeficiency

13. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and TB testing in line withlocal practice)

14. Female patients who are pregnant or breastfeeding or male or female patients ofreproductive potential who are not willing to employ effective birth control fromscreening to 90 days after the last dose of the trial treatment.

15. Known allergy or hypersensitivity to any of the study drugs or any of the study drugexcipients.