New drug cocktail targets Hard-to-Treat liver cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 containing sarcomatoid or intrahepatic cholangiocarcinoma components. Hematologic malignancies. History of hepatic encephalopathy or prior liver transplantation. Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage; asymptomatic small effusions allowed. Active HBV (HBV DNA \>2000 IU/mL) or HCV (HCV RNA \>10\^3 copies/mL) infection; co-infection HBsAg+/HCV Ab+ excluded. CNS metastases. Significant recent variceal bleeding (within 6 months). Life-threatening hemorrhagic events within 3 months. Significant thromboembolic events within 6 months. Use of high-dose aspirin (\>325 mg/day) or other platelet inhibitors within 2 weeks prior to first dose. Unresolved grade ≥2 toxicities from prior therapies (excluding hair loss or asymptomatic lab abnormalities). Symptomatic heart failure NYHA II-IV or LVEF \<50%. Uncontrolled arrhythmias or congenital long QT syndrome, QTc \>500 ms. Active bleeding disorders or on thrombolytic therapy. Recent history of gastrointestinal perforation, fistula, obstruction, or significant bowel disease. Radiotherapy within 3-7 weeks prior to first dose with residual toxicity. History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-induced lung injury, or severe impaired lung function. Active tuberculosis or treatment for TB within 1 year. HIV infection or active, untreated syphilis. Active or uncontrolled severe infection within 4 weeks prior to first dose. Active autoimmune disease requiring systemic treatment within 2 years. Known primary immunodeficiency. Use of systemic immunosuppressants within 4 weeks prior to first dose (nasal/inhaled steroids at physiologic dose allowed). Receipt of live attenuated vaccines within 4 weeks prior to first dose. Major surgery within 4 weeks prior to first dose, or unhealed wounds. Minor procedures like IV lines excluded. Uncontrolled metabolic disorders or organ/systemic disease posing excess risk. History of other malignancy within 5 years, except curatively treated basal cell carcinoma, squamous cell carcinoma, or in situ carcinoma. Known hypersensitivity to study drugs or formulation components. History of aortic dissection or visceral artery aneurysm. Participation in another clinical trial within 4 weeks prior to first dose. Pregnant or breastfeeding women. Extensive metastatic disease (≥5 lesions) or major vascular invasion. Other acute or chronic diseases, psychiatric conditions, or lab abnormalities deemed by investigator to increase risk or interfere with study.