PRIMARY OBJECTIVE:~I. To assess proportion of participants that are progression-free at 6 months.~SECONDARY OBJECTIVES:~I. To assess objective response rate (ORR) for study intervention. II. To assess disease control rate (DCR) for study intervention. III. To assess time to disease progression (TTP) for study intervention. IV. To observe progression-free survival. V. To observe overall survival (OS) for study intervention. VI. To assess safety of study intervention.~EXPLORATORY OBJECTIVE:~I. To evaluate therapy induced changes in the tumor and tumor immune microenvironments.~OUTLINE:~CYCLE 1: Patients receive atezolizumab intravenously (IV) over 60 minutes on day 1. Within 14 days, patients receive yttrium Y 90 glass microspheres (Y-90) intra-arterially.~CYCLES 2+: Patients receive atezolizumab IV over 60 minutes on day 1 and cabozantinib S-malate (cabozantinib) orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for a total of 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit may continue receiving atezolizumab and cabozantinib beyond cycle 12 at the discretion of the principal investigator (PI).~After completion of study treatment, patients are followed up at 30 days and then every 6 months until 2 years from first dose of study drug.
This phase II trial tests whether yttrium Y 90 glass microspheres, atezolizumab, and cabozantinib work to shrink tumors in patients with liver cancer (hepatocellular carcinoma) that cannot be removed by surgery (unresectable) or that has spread to nearby tissue or lymph nodes (locally advanced). Yttrium Y 90 glass microspheres consists of millions of microscopic glass spheres containing yttrium-90, a radioactive substance. Yttrium Y 90 glass microspheres are delivered to the tumor in the liver through a catheter in an artery. Radiation from the Yttrium-90 helps treat the tumor. 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 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The combination of yttrium Y 90 glass microspheres, atezolizumab, and cabozantinib may kill more tumor cells.