Clinical Research Directory

Inclusion Criteria: * Age 18 to 75 years, male or female, and willing to provide written informed consent. * Hepatocellular carcinoma (HCC) confirmed by histologic/cytologic examination or diagnosed according to accepted guideline-based clinical criteria. * Unresectable HCC as determined by multidisciplinary evaluation; BCLC stage B disease that is unsuitable for, declined, or has progressed after locoregional treatment, or BCLC stage C disease; candidate for first-line systemic therapy. * No prior systemic anticancer therapy for unresectable HCC. Prior locoregional treatment must have been completed at least 4 weeks before the first study treatment, with treatment-related toxicities recovered to Grade ≤1 or baseline. * At least one measurable lesion according to RECIST version 1.1. The measurable lesion must not have received prior locoregional treatment unless unequivocal radiologic progression has subsequently occurred. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and life expectancy of at least 12 weeks. * Child-Pugh class A (score 5-6), without clinically decompensated ascites or hepatic encephalopathy. * Adequate bone marrow function: absolute neutrophil count ≥1.5 × 10\^9/L, platelet count ≥75 × 10\^9/L, and hemoglobin ≥90 g/L. * Adequate hepatic and renal function: total bilirubin ≤3 × upper limit of normal (ULN); AST and ALT ≤5 × ULN; albumin ≥28 g/L; INR ≤1.5; serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min. * Urine protein dipstick ≤1+. If urine protein is ≥2+, 24-hour urinary protein must be \<1 g. Blood pressure must be adequately controlled at ≤150/90 mmHg. * Upper gastrointestinal endoscopic evaluation within 6 months before the first study treatment. Intermediate- or high-risk gastroesophageal varices must have been appropriately managed and considered to have an acceptable bleeding risk by the investigator. * Participants with positive HBsAg or detectable HBV DNA must receive appropriate antiviral therapy and have HBV DNA \<500 IU/mL before the first study treatment. HCV infection must be clinically stable. * Serum vitamin B12 at or above the institutional lower limit of normal, with no uncorrected megaloblastic anemia or progressive unexplained neurologic symptoms. * Participants of reproductive potential must agree to use highly effective contraception according to protocol requirements. Exclusion Criteria: * Prior treatment with PD-1, PD-L1, CTLA-4, or other immune checkpoint inhibitors, or prior bevacizumab treatment for HCC. * Eligible for curative resection, ablation, or liver transplantation and willing to undergo such treatment. * Active or recent clinically significant bleeding, including gastrointestinal bleeding, hemoptysis, or other Grade ≥2 bleeding within 6 months before the first study treatment, or untreated high-risk varices. * Arterial thromboembolism, myocardial infarction, unstable angina, stroke/transient ischemic attack, severe arrhythmia, or NYHA class \>II heart failure within 6 months before the first study treatment. * Tumor invasion of major blood vessels considered by the investigator to confer a significant near-term risk of fatal bleeding, or clinically significant risk of tumor rupture. * Uncontrolled hypertension, clinically significant proteinuria, active peptic ulcer disease, high risk of gastrointestinal perforation or fistula, unhealed wound, or major surgery within 28 days before the first study treatment. * Active autoimmune disease requiring systemic treatment, or systemic corticosteroid therapy equivalent to prednisone \>10 mg/day or other immunosuppressive therapy within 14 days before the first study treatment, except physiologic replacement therapy. * Prior solid-organ transplantation or allogeneic hematopoietic stem-cell transplantation. * Active severe infection, including uncontrolled HBV or HCV infection, active tuberculosis, or HIV infection associated with clinically significant immunodeficiency. * Symptomatic, untreated, or unstable central nervous system metastases. * Vitamin B12 deficiency, pernicious anemia, folic acid hypersensitivity, or continuous use of folic acid \>0.4 mg/day within 14 days before screening that cannot be discontinued. * Current use of methotrexate or other antifolate drugs, or use of phenytoin, phenobarbital, or primidone that cannot be replaced or appropriately monitored. * Pregnancy or breastfeeding; serious concurrent disease, psychiatric or cognitive disorder, or compliance issue that could interfere with study participation. * Participation in another interventional clinical study within 4 weeks before the first study treatment, or any other condition considered by the investigator to make the participant unsuitable for enrollment.