Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer

PRIMARY OBJECTIVE: I. To determine the progression-free and overall survival in subjects with advanced hepatocellular carcinoma who previously progressed on atezolizumab/bevacizumab who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. SECONDARY OBJECTIVES: I. To determine the overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 response in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. II. To determine the duration of response in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. III. To determine the safety profile of adding atezolizumab to multi-kinase inhibitor in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone. EXPLORATORY OBJECTIVE: I. To explore for potential predictive biomarkers for response and resistance to anti-PD-L1 and/or multi-kinase inhibitor therapy in subject population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 and cabozantinib orally (PO) once daily (QD) or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed-up every 9 weeks for up to 2 years.