Cadonilimab and Lenvatinib for Conversion Therapy in Unresectable Hepatocellular Carcinoma

Exclusion Criteria

• •Previously histologically/cytologically confirmed hepatocellular carcinoma with fibrolamellar components, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.
• •Prior local or systemic anti-tumor therapy. History of hepatic encephalopathy. History of liver transplantation. Clinically significant pericardial effusion requiring drainage or clinically symptomatic pleural effusion.
• •Clinically evident ascites defined as detectable on physical examination or requiring drainage during screening.
• •Concurrent HBV and HCV infection (HCV RNA negative patients with a history of HCV infection are considered uninfected).
• •Central nervous system metastasis or leptomeningeal metastasis. History of esophageal or gastric variceal bleeding due to portal hypertension in the first 6 months before the initial dose. Participants must have undergone esophagogastroduodenoscopy within 6 months before the first dose; participants with severe (Grade 3) varices are not allowed to participate in the study.
• •Patients with any bleeding diathesis signs or history, experiencing any bleeding or hemorrhagic events ≥CTCAE Grade 3 within the first 4 weeks before the initial dose.
• •Uncontrolled hypertension, with systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg after optimal medical treatment, hypertensive crisis, or a history of hypertensive encephalopathy.
• •Symptomatic congestive heart failure (New York Heart Association Class II-IV) or echocardiographic left ventricular ejection fraction (EF) \<50%. Symptomatic or poorly controlled arrhythmias, including atrial fibrillation or flutter with a ventricular rate \>100 beats/min, a history of congenital long QT syndrome, or a corrected QT interval (QTc) \>450 ms (male) or QTc \>470 ms (female) on screening (using the Fridericia method). A history of myocarditis, cardiomyopathy, or malignant arrhythmias.
• •Severe bleeding tendency or coagulation disorders, or receiving thrombolytic therapy. Currently using or recently used (within 10 days before the first dose of study treatment) aspirin (\>325 mg/day) or anticoagulants requiring INR monitoring (such as warfarin).
• •History of gastrointestinal perforation and/or fistula within the first 6 months before the initial dose, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive colon resection (partial colon resection or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.
• •Received radiation therapy within the first 3 weeks before the initial dose. Patients who received radiation therapy more than 7 days before the first dose can be enrolled. Presence of interstitial lung disease or interstitial lung disease requiring steroid treatment, either past or current.
• •Active pulmonary tuberculosis (TB), receiving anti-TB treatment, or having received anti-TB treatment within the past 1 year before the initial dose.
• •Subjects with any active autoimmune disease or a history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, and those who have undergone thyroid surgery cannot be included). Subjects with resolved childhood asthma without the need for intervention can be included; subjects with asthma requiring bronchodilators for medical intervention cannot be included.
• •Subjects using immunosuppressive agents, either systemic or locally absorbable steroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent), and still continuing within the last 2 weeks before enrollment.
• •Subjects with active infection or unexplained fever \>38.5°C during screening or within the first 4 weeks before the initial dose (subjects with fever related to tumor-induced fever can be included according to the investigator's judgment).
• •Patients with objective evidence of past or present lung fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severe impairment of lung function.
• •Subjects with congenital or acquired immunodeficiency, such as HIV infection. Subjects who have not received live vaccines within 4 weeks before the study medication or may receive live vaccines during the study period.
• •Subjects with a known history of substance abuse, alcohol abuse, or drug abuse. Patients unable to take oral medication. The investigator deems it necessary to exclude subjects from this study. For instance, based on the investigator's judgment, if a participant has other factors that could potentially lead to the premature termination of the study, such as the presence of other serious illnesses (including mental disorders) requiring concurrent treatment, severe gastroesophageal varices, significant laboratory abnormalities, or factors related to family or social circumstances that could impact the safety of the participant or the collection of data and samples.