Major objectives To evaluate the efficacy of lparomlimab and Tuvonralimab injection (QL1706, an Anti-PD-1/ CTLA-4 Combined Antibody) in combination with TACE and lenvatinib as second-line therapy in patients with unresectable intermediate-to-advanced hepatocellular carcinoma.

This single-arm, single-center clinical study aims to evaluate the efficacy and safety of lparomlimab and Tuvonralimab injection (QL1706, an Anti-PD-1/ CTLA-4 Combined Antibody) in combination with TACE and lenvatinib as second-line therapy in patients with unresectable intermediate-to-advanced hepatocellular carcinoma. This study consists of three phases: screening, treatment, and follow-up. Efficacy evaluation and safety monitoring should be performed throughout the study.

Inclusion Criteria:

• Comprehension and voluntary signing of the study's informed consent form;

• Age ≥18 years, any gender;

• Histologically or clinically confirmed hepatocellular carcinoma;

• Documented failure or intolerance to first-line therapy with PD-1/PD-L1 inhibitor plus bevacizumab;

• ECOG performance status 0-2;

• Child-Pugh class A or class B (score ≤7) without hepatic encephalopathy history;

• Life expectancy ≥3 months;

• At least one measurable target lesion confirmed by screening imaging per RECIST v1.1;

• Adequate organ and bone marrow function within 7 days prior to initial study treatment;

• Active HBV/HCV infection requires ongoing antiviral therapy; k.Fertile patients must use highly effective contraception with partners during treatment and ≥180 days post-last dose.

  2.Exclusion Criteria:

• Inability to comply with the study protocol or procedures;

• Histologically/cytologically confirmed fibrolamellar HCC, sarcomatoid HCC, cholangiocarcinoma, or mixed hepatocellular-cholangiocarcinoma;

• History of liver transplantation or planned transplantation;

• Presence of central nervous system metastases and/or leptomeningeal carcinomatosis;

• Baseline imaging showing Vp4 portal vein tumor thrombosis;

• Hypersensitivity to any study drug components or history of severe allergic reactions;

• Concurrent HBV and HCV co-infection;

• Clinically significant ascites requiring intervention during screening;

• Concurrent use of other investigational drugs or participation in another clinical trial within 4 weeks prior to enrollment;

• Esophageal/gastric variceal bleeding due to portal hypertension within 6 months before treatment initiation, or high-risk varices on endoscopy within 3 months;

• Current interstitial lung disease (ILD), history of steroid-required ILD, or other pulmonary fibrosis/organizing pneumonia affecting immune-related pulmonary toxicity assessment;

• Uncontrolled hypertension (SBP≥160 mmHg and/or DBP≥100 mmHg despite medication), coronary artery disease, arrhythmias, or heart failure (NYHA Class ≥II);

• Uncontrolled clinically significant infections requiring IV antimicrobial therapy;

• Proteinuria ≥2+ (≥1.0g/24h);

• History of hemorrhagic tendency regardless of severity within 2 months prior to enrollment;

• Arterial/venous thromboembolic events within 12 months before treatment initiation (e.g., cerebrovascular accident including TIA);

• Acute myocardial infarction, acute coronary syndrome, or CABG within 6 months before treatment;

• Unhealed fractures or chronic non-healing wounds;

• Coagulopathy, bleeding diathesis, or current therapeutic anticoagulation;

• Other malignancies within 5 years except curatively resected basal/squamous cell skin carcinoma or cervical carcinoma in situ;

• Active autoimmune disease or autoimmune disease history requiring immunosuppression within 4 weeks prior to enrollment;

• Prior allogeneic bone marrow or solid organ transplantation;

• Investigator assessment of ineligibility based on medical/safety reasons.