This is a Phase II, randomized, open-label, global, multi-center study to compare the efficacy and safety of AK104 in combination with lenvatinib versus lenvatinib in patients with advanced hepatocellular carcinoma who have progressed on the first line treatment of atezolizumab and bevacizumab.

Inclusion Criteria:

1. Signed the Informed Consent Form (ICF) voluntarily.
2. Age ≥18 years at time of signing ICF.
3. Histologic or cytologic confirmation of HCC, or clinical diagnosis of HCC as per AASLD criteria.
4. BCLC stage B or C, and not suitable for curative surgical or local therapy.
5. Participants have progressed on the prior first-line systemic treatment with atezolizumab plus bevacizumab combination treatment.
6. At least one measurable lesion according to RECIST v1.1.
7. Child-Pugh Class A .
8. ECOG performance status of 0 or 1.
9. With a life expectancy of ≥3 months.
10. Adequate organ and hematologic function.

Exclusion Criteria:

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
2. Tumor thrombus invasion of superior mesenteric vein.
3. Has a known history of, or any evidence of CNS metastases.
4. Has received anti-cancer therapy for HCC within 3 weeks prior to the first dose of study treatment.
5. Has received systemic anti-cancer therapy other than atezolizumab and bevacizumab.
6. Has participated in another clinical study within 4 weeks prior to the first dose.
7. History of liver transplantation.
8. History of hepatic encephalopathy.
9. Clinically symptomatic or recurrently drained pleural effusion, pericardial effusion, or ascites.
10. History of bleeding event due to esophageal and/or gastric varices within 6 months prior to the first dose of study treatment.