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.
This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.