A Platform Trial for Personalized and Adaptive Therapies in Hepatocellular Carcinoma

Inclusion Criteria: * Written informed consent obtained. * Age ≥ 18 years at time of study entry. * Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients. * Patients who have previously received first-line therapy with anti-PD-1/PD-L1 combined with anti-VEGF antibodies, or anti-PD-1/PD-L1 combined with TKI, or anti-PD-1/PD-L1 combined with anti-CTLA-4 antibodies and experienced disease progression; or disease recurrence within 6 months after completion of neoadjuvant/adjuvant immunotherapy. * At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1. * 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 …