A Phase II Clinical Study of AK104/AK112 in Combination With TT-00420 Tablet for Advanced HCC.

Inclusion criteria

• Age ≥ 18 and ≤ 75 years.
• Histologically or cytologically confirmed hepatocellular carcinoma, or meets the clinical diagnostic criteria for hepatocellular carcinoma.
• Barcelona Clinic Liver Cancer (BCLC) stage C; or stage B and assessed by the investigator as unsuitable for curative topical treatment.
• For cohorts A and B: No prior systemic anti-cancer treatment for hepatocellular carcinoma.
• At least one measurable lesion according to RECIST v1.1 criteria.
• Child-Pugh liver function score ≤7. ECOG performance status of 0 or 1.
• Clinically controllable HBV or HCV infection.
• Adequate organ and bone marrow function.

Exclusion criteria

• Previous histologically or cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.
• Diagnosed with another malignancy within 3 years.
• History of hepatic encephalopathy.
• Presence of clinically significant pericardial effusion; symptomatic pleural effusion requiring drainage or moderate to severe ascites uncontrolled by diuretics.
• Concurrent infection with HBV and HCV.
• Presence of central nervous system metastases or meningeal metastases.
• Esophageal or gastric variceal bleeding within 6 months. Imaging (CT or MRI) shows extrahepatic metastasis invading major blood vessels or indistinct vascular boundaries, with high bleeding risk assessed by the researcher.
• Liver tumor volume exceeding 50% of total liver volume; portal vein main trunk tumor thrombus or tumor thrombus in contralateral main branch of the portal vein, or mesenteric vein tumor thrombus; presence of inferior vena cava thrombus or involvement of the heart.
• Received topical treatment for liver cancer, any systemic anti-tumor drugs, or other clinical trial drugs within 4 weeks prior to the first administration.
• Unable to swallow, or has severe gastrointestinal disease or gastrointestinal dysfunction. History of intestinal obstruction or intestinal perforation within 6 months.
• Uncontrolled hypertension, symptomatic heart failure, symptomatic or poorly controlled arrhythmia, myocarditis, cardiomyopathy, history of malignant arrhythmias.
• Participants with severe bleeding tendencies or coagulation disorders.
• Active pulmonary tuberculosis, active syphilis, or history of HIV infection.
• Severe infection within 4 weeks prior to the first administration, or received systemic anti-infective treatment within 14 days.
• Other conditions with high medical risk or secondary tumor symptoms, which, in the judgment of the researcher, make the participant unsuitable for participation in the study.