Neoadjuvant Triple Therapy for Resectable HCC

Inclusion criteria

• Voluntarily join the study and sign the informed consent form.
• Male or female patients aged between 18 and 75 years.
• Child-Pugh class A.
• Indocyanine green 15-minute retention rate (ICGR-15) < 15%.
• ECOG performance status 0-1.
• Diagnosed with hepatocellular carcinoma (HCC) according to the "Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2022 Edition)."
• BCLC stage A or B, with a single tumor larger than 5 cm or multiple tumors, and considered surgically resectable after multidisciplinary discussion.
• According to RECIST 1.1 criteria, the patient has at least one measurable lesion (a measurable lesion with a long diameter ≥ 10 mm on CT/MRI scan, and the measurable lesion has not received local treatments such as radiotherapy or cryotherapy).
• Blood routine: absolute neutrophil count ≥ 1.5 × 10^9/L, Hb ≥ 8.5 g/L, PLT ≥ 75 × 10^9/L.
• No history of severe arrhythmia, heart failure, severe pulmonary ventilation disorders, or severe lung infections; no acute or chronic renal failure, and creatinine clearance rate > 40 mL/min.
• Women of childbearing potential must agree to use contraception during the medication period and for 6 months after the end of medication; have a negative serum or urine pregnancy test within 7 days prior to enrollment, and must not be breastfeeding. Men must agree to use contraception during the study period and for 6 months after the end of the study.

Exclusion criteria

• Tumor rupture with bleeding or suspected abdominal cavity metastasis.
• Previous treatment with any antitumor therapies before enrollment, such as targeted drugs, PD-1/PD-L1/CTLA-4 monoclonal antibodies, surgery, TACE, FOLFOX systemic chemotherapy, radiotherapy, and Huaier granules.
• History of allergy to lenvatinib, cadonilimab, or their components.
• Presence of any active autoimmune disease or a history of autoimmune disease with expected recurrence (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes); hypothyroidism treated with stable doses of thyroid replacement hormone; type 1 diabetes mellitus treated with stable doses of insulin; excluding patients with vitiligo or childhood asthma/allergies that have resolved and require no intervention in adulthood.
• History of immunodeficiency; patients using immunosuppressive drugs or systemic corticosteroids for immunosuppressive purposes and who have continued using them within 2 weeks before signing the informed consent form.
• Known hereditary or acquired bleeding (e.g., coagulopathy) or thrombotic tendency, such as hemophilia; currently receiving or recently (within 10 days before the start of study treatment) receiving full-dose oral or injectable anticoagulants or thrombolytics for therapeutic purposes (prophylactic use of low-dose aspirin and low-molecular-weight heparin is allowed).
• Severe infection within 4 weeks before the first use of the study drug (CTC AE grade > 2), such as severe pneumonia requiring hospitalization, bacteremia, or infection complications; baseline chest imaging indicating active lung inflammation; symptoms and signs of infection within 2 weeks before the first use of the study drug or requiring oral or intravenous antibiotic treatment (excluding prophylactic antibiotic use).
• Urinalysis indicating proteinuria ≥ 1+; if so, a 24-hour urine protein test is required; patients with 24-hour urine protein ≥ 1 g.
• History of other malignancies within the past 5 years or concurrently, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid carcinoma.
• Patients with concomitant psychiatric disorders; history of substance abuse, alcohol, or drug addiction.
• Pregnant or breastfeeding women.
• Patients with significant surgical contraindications, such as renal and cardiopulmonary insufficiency, as judged by the investigator, or any other reasons deemed unsuitable for participation in this trial by the investigator.