A Clinical Trial of Firsekibart, Tislelizumab, and Lenvatinib in Patients With Unresectable, TP53-Mutated Hepatocellular Carcinoma

Inclusion Criteria: * Ability to understand and sign written informed consent prior to any study-related procedures. Age ≥18 years at the time of signing informed consent. Histologically or cytologically confirmed advanced or unresectable hepatocellular carcinoma (HCC). Documented disease progression after prior systemic immunotherapy, including at least one PD-(L)1 inhibitor. Confirmed TP53 mutation in fresh liver tumor tissue by central laboratory testing. Determined by liver tumor MDT to be unsuitable for curative surgery (R0 resection not feasible, insufficient normal liver volume, or other criteria). BCLC stage B or C. At least one measurable lesion per RECIST v1.1 confirmed by BICR. ECOG performance status 0-1. Child-Pugh class A within 7 days prior to randomization. Adequate organ and bone marrow function within 7 days prior to enrollment: ANC ≥1.5×10\^9/L, Platelets ≥75×10\^9/L, HGB ≥9 g/dL TBIL ≤2×ULN, ALT/AST ≤5×ULN, Albumin ≥28 g/L, ALP ≤5×ULN Creatinine ≤1.5×ULN or CCr ≥50 mL/min, urine protein \<2+ (or 24-h urine protein \<1 g if baseline ≥2+) INR ≤2.3 or PT prolongation ≤6 sec Expected survival ≥12 weeks. Women of childbearing potential and male participants with partners of childbearing potential must use effective contraception during treatment and for 6 months after last dose. Ability and willingness to comply with study procedures and visits. Exclusion Criteria: * Candidates suitable for local curative therapy. Mixed liver tumors contain…