Study of Atezolizumab and Bevacizumab With Y-90 TARE in Patients With Unresectable Hepatocellular Carcinoma (HCC)

Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Patients must be willing and able to provide written informed consent for this trial. * Age ≥ 18 years at the time of consent. * ECOG Performance Status of 0-1 at screening * Histological or cytological evidence/confirmation per AJCC, 8th edition, of hepatocellular carcinoma (HCC). * Measurable disease by RECIST 1.1. * Patients must have a Child-Pugh score of A. or selected B7. NOTE: Definition of the selected B7 patients: Child Pugh B7 patients are allowed if they meet the inclusion criteria 11 and they do not have hepatic encephalopathy or more than a moderate amount of ascites. * Patients must have at least Barcelona Clinic Liver Cancer (BCLC) stage B HCC and must be outside of Milan Criteria; and/or HCC peripheral vascular involvement of any size or number of tumor (segment peripheral, vp1 and vp2 are allowed, but vp3 and vp4 are excluded). NOTE: absence of extrahepatic spread, must be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) scan of the chest, abdomen, and pelvis. * Patient must either (1) not be a candidate for liver transplantation as determined by the liver transplant service or (2) refuse evaluation for transplantation. * Archival tissue obtained within 6 months of registration is required. If archival tissue is not available, subjects are not eligible. * No prior systemic therapy is permitted. NOTE: Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound or TACE) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST 1.1. Prior TACE is allowed if FLR is ≥ 40%. * Patient must be a TARE candidate, as defined by a lung dose threshold for Y-90 of 30Gy and an estimated (future liver remnants) FLR of ≥ 40% at the time of forming the comprehensive treatment plan. Both the lung dose threshold and FLR values must be obtained and available in source documentation. * Patients must demonstrate adequate hepatic, bone marrow, and renal function as defined below. All screening labs should be performed within 14 days of treatment initiation. * Hematological * Lymphocyte Count: 500/μL * Absolute Neutrophil Count (ANC): ≥ 1,500 /μL * Hemoglobin (Hgb): ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment) * Platelet count (Plt): ≥ 75,000 / μL * Renal ---Serum creatinine OR Measured or calculated CrCl (GFR can also be used in place of creatinine or CrCl): ≤ 1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN * Hepatic * Bilirubin: ≤ 3.0 * Aspartate aminotransferase (AST): ≤ 5 X ULN for subjects with cancer in liver * Alanine aminotransferase (ALT): ≤ 5 X ULN for subjects with cancer in liver * Albumin: \> 2.5 mg/dL * Urine Protein: Urine dipstick for proteinuria ≤ 2 g (within 14 days prior to initiation of study treatment). Patients discovered to have \>2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours. * Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 X ULN * Calcium-Subjects with uncontrolled or symptomatic hypercalcemia are NOT eligible * Ionized Calcium: \< 1.5 mmol/L * Serum Calcium OR Corrected serum calcium: \< 12 mg/dL OR \< ULN * Documented virology status of HIV; NOTE: Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load. * Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test: For patients with active hepatitis B virus (HBV): HBV DNA \<500 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study. * Subjects with chronic infection by HCV who are untreated or who failed previous therapies for HCV are allowed on study. In addition, subjects with successful HCV treatment (defined as sustained virologic response \[SVR\] 12 or SVR 24) are allowed as long as patients are not actively receiving anti-HCV treatment at the time of study enrollment. Investigators can stop anti-HCV treatment at their discretion prior to enrolling patients on study. * Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to study treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. * Female participants of childbearing potential must be willing to abstain from heterosexual intercourse or to use contraception as outlined in Section 5.6. Male participants capable of fathering children must be willing to abstain from heterosexual intercourse or to use contraception as outlined in Section 5.6. * As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. Exclusion Criteria Subjects meeting any of the criteria below may not participate in the study: * Have signs of liver failure, e.g. clinically significant ascites, encephalopathy, or variceal bleeding within six months from enrollment. * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX® are allowed. * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding. * Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment. NOTE: Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure. * Have evidence of excessive hepatopulmonary shunting (\> 20% in 99mTc macro-aggregated albumin scan for resin and 30 Gy per treatment for glass) or angiographically demonstrable and non-occludable gastrointestinal shunting, precluding from Y-90 treatment. * Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure \> 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. NOTE: Anti-hypertensive therapy to achieve these parameters is allowable. * Prior history of hypertensive crisis or hypertensive encephalopathy. * Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina. * Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. * Major surgery within 4 weeks prior to registration or anticipation of a major surgical procedure during study. * Have had prior transplant of any kind (stem cell or solid organ). * Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: * Rash must cover \< 10% of body surface area * Disease is well controlled at baseline and requires only low-potency topical corticosteroids * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months * Have history of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * Treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1 and anti-PD-L1 therapeutic antibodies. * Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment. * Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after sponsor-investigator confirmation has been obtained. * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study * Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry. * Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. * Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment. * Patients with brain metastases. * Have unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute (NCI) CTCAE v5 grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria. NOTE: Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by any of the investigational products may be included (e.g., hearing loss) after consultation with the sponsor-investigator. * Diagnosed or treated for malignancy other than HCC, unless they meet one of the following exceptions: * Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before registration and felt to be at low risk for recurrence by the treating physician. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated cervical carcinoma in situ without evidence of disease. * Have a known or suspected allergy to bevacizumab or atezolizumab or known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation. * Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment. * History of hemoptysis (≥ 2.5 mL of bright red blood per episode) within 1 month prior to initiation of study treatment. * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). * Current or recent (within 10 days of first dose of study treatment) use of aspirin (≥325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol. * Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. NOTE: Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR ≤1.5 x ULN and aPTT is within normal limits within 14 days prior to initiation of study treatment. * Have an uncontrolled intercurrent illness including, but not limited to any of the following: * Psychiatric illness/social situations that would limit compliance with study requirements * Have any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications. * Active alcohol use, drug use, or a psychiatric disease that would, in the opinion of the sponsor-investigator or a sub-investigator (sub-I), prevent the subject from complying with the study protocol and/or endanger the subject during their participation in the study. * Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. NOTE: Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. * Active tuberculosis. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). * Have received a live attenuated vaccine (e.g., FluMist®) within 30 days of the planned start of study therapy and 180 days after the last dose of the study treatment. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * Have received or are receiving any investigational therapy within 28 days prior to the first dose of bevacizumab and atezolizumab. NOTE: Subjects may be enrolled in an observational (non-interventional) clinical study or in the follow-up period of an interventional study.