• Written informed consent obtained.

• Age ≥ 18 years at time of study entry.

• Barcelona Clinic Liver Cancer stage C, or stage B not amenable to curative or locoregional therapies.

• HCC confirmed by radiology, histology or cytology.

• No prior systemic therapy for HCC.

• At least one measurable site of disease as defined by RECIST1.1criteria with spiral CT scan or MRI.

• Child-Pugh scores 5-7, performance status (PS) ≤ 2 (ECOG scale).

• Subjects with chronic HBV infection must have HBV DNA viral load \< 100 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy.

• Life expectancy of at least 12 weeks.

• Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥60 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula)

• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.

• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.