This is a Phase III, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of atezolizumab plus either lenvatinib or sorafenib versus lenvatinib or sorafenib alone in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have progressed on prior systemic treatment with atezolizumab plus bevacizumab combination.

Inclusion Criteria:

• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
• Disease progression following prior atezolizumab plus bevacizumab combination treatment for HCC, for at least 4 consecutive treatment cycles, and 2 subsequent tumor assessments. It is required that at least 1 tumor assessment shows either stable disease (SD), partial response (PR), or complete response (CR).
• At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7 days prior to randomization
• Child-Pugh class A within 7 days prior to randomization
• Adequate hematologic and end-organ function

Exclusion Criteria:

• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• History of leptomeningeal disease
• History of hepatic encephalopathy, preceding 6 months, unresponsive to therapy within 3 days
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing