Atezolizumab and Bevacizumab in Combination With TACE for Patients With BCLC B HCC

Inclusion Criteria: * At least 18 years old * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 28 days prior to registration * No cirrhosis or Child-Pugh A cirrhosis * Diagnosis of HCC either by imaging or biopsy * Evidence of HCC that meets BCLC B criteria * Patients must have adequate hepatic, bone marrow, and renal function. All screening labs should be performed within 14 days of treatment initiation. * Patients must be candidates for TACE treatment that can be treated in up to 4 sessions * Patients who are positive for Hepatitis B (HBc), regardless of HBs status, and have an undetectable Hepatitis B virus (HBV) viral load do not require HBV antiviral prophylaxis * Patients who are not on HBV therapy, but positive for Hepatitis B surface antigen (HBsAg) and have an undetectable viral load are eligible for the study as long as they begin anti-viral prophylaxis prior to the start of study treatment * Patients can have untreated hepatitis C * At least one unidimensional tumor measurable by RECIST v1.1 criteria * Hg ≥ 9 g/dL * Creatinine less than 1.5 x ULN * Serum bilirubin \< 2.5 mg/dl * Aspartate Transferase (AST) \< 5X upper limit of normal (ULN) * Alanine Transaminase (ALT) \< 5X ULN * Platelet count \> 100 x 10\^9/L * Patients must have an EGD within 6 months with no evidence of esophageal and/or gastric varices with bleeding or high risk of bleeding. Patients with varices must be assessed and treated per local standard-of-care prior to enrollment. * Ability to comply with the study protocol, in the investigator's judgment * Life expectancy ≥ 6 months * Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: * Absolute Neutrophil Count (ANC) ≥1.5 · 10\^9/L (1500/ÍL) without granulocyte colony-stimulating factor support * Lymphocyte count ≥ 0.5 ∙ 10\^9/L (500/ÍL) * Serum albumin ≥ 25 g/L (2.5 g/dL) * For patients not receiving therapeutic anticoagulation: International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 ∙ ULN * For patients receiving therapeutic anticoagulation: stable anticoagulant regimen allowed for both Atezo and Avastin. Please note the most current guidelines for Avastin are: Exclusionary: Current or recent (\< 10 days prior to initiation of study treatment) use of aspirin (\> 325 mg/day), or clopidogrel (\> 75 mg/day) Allowed: Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk. * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below. Women of child-bearing potential must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 6 months after the final dose of atezolizumab and bevacizumab. Women must refrain from donating eggs during this same period. 1. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). 2. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. 3. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. * For men of childbearing potential: With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of atezolizumab and bevacizumab to avoid exposing the embryo. Men must refrain from donating sperm during this same period. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible Exclusion Criteria: * Patients must not have signs of liver failure or history of liver failure e.g. - encephalopathy or variceal bleeding * Uncontrolled hepatitis B infection with viral load \>500 IU/ml * History of hypertensive crisis or hypertensive encephalopathy * Patients who are candidates for curative intent therapy (transplant, resection, or thermal ablation) or liver transplant * Patients who are on the transplant list * Ascites requiring therapeutic paracentesis in the last 12 months * Episode of hepatic encephalopathy in the last 12 months * Extrahepatic spread: borderline portal lymph nodes deemed to be of indeterminate nature and measuring less than 2 cm are allowed * Prior local or systemic therapy for HCC or prior TACE, excluding prior use of Radiofrequency Ablation (RFA) * Patients cannot have known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC * Occlusion of the hepatic artery or main portal vein * Pregnant or lactating, or intending to become pregnant during the study * Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or other recombinant human antibodies * Known history of Human Immunodeficiency virus (HIV) infection. No HIV testing is required. * Active or history of autoimmune disease or immune deficiency, 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 (see Appendix 8 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions: 1. Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. 2. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. 3. 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: i. Rash must cover \< 10% of body surface area ii. Disease is well controlled at baseline and requires only low-potency topical corticosteroids iii. 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 * History of leptomeningeal disease * Active tuberculosis * Uncontrolled tumor-related pain a. Patients requiring pain medication must be on a stable regimen at study entry. * Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN) * Signs or symptoms of significant infection within 2 weeks prior to Day 1 * Severe infection within 4 weeks prior to initiation of study treatment, including but not limited hospitalization for complications of infection, bacteremia, or severe pneumonia. * Received therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day 1 * Significant cardiovascular disease, (such as New York Heart Association cardiac disease Class II or greater, myocardial infarction, or cerebrovascular accident) within 3 months prior to prior to Day 1, unstable arrhythmias, or unstable angina * Patients with a known left ventricular ejection fraction (LVEF) \< 40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. * History of stroke, prolonged reversible ischemic neurological deficit or transient ischemic attack within 6 months prior to Day 1 * Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the study * Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to initiation of study treatment, during treatment with atezolizumab, and for 5 months after the last dose of atezolizumab. * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study * Malignancies within 2 years prior to study start, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year Overall Survival (OS) \> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent) * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) a. Patients with indwelling catheters (e.g., PleurX®) are allowed. * Inadequately controlled arterial hypertension (defined as systolic blood pressure \[BP\] ≥150 mmHg and/or diastolic BP \>100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. Anti-hypertensive therapy to achieve these parameters is allowable * Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 * History of hemoptysis (≥ 2.5 mL of bright red blood per episode) within 1 month prior to Day 1 * Evidence of bleeding diathesis or significant coagulopathy * 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 (\< 10 days prior to initiation of study treatment) use of aspirin (\> 325 mg/day), or clopidogrel (\> 75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk. * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days of treatment start * Proteinuria, as demonstrated by urine dipstick or ≥1.0 g of protein in a 24-hour urine collection. All patients with ≥2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein. * Chronic daily treatment with a nonsteroidal anti-inflammatory drug (occasional use for the symptomatic relief of medical conditions such as headache or fever is allowed) * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. * Prior allogeneic stem cell or solid organ transplantation * Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti- cytotoxic T-lymphocyte associated protein 4 (CTLA-4), anti- Programmed cell death protein 1 (PD-1), and anti- Programmed death-ligand 1 (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 investigational therapy within 28 days prior to initiation of study treatment * Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation * Known allergy or hypersensitivity to any component of the bevacizumab or atezolizumab formulation * History of Grade ≥ 4 venous thromboembolism * History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization * Serious, non-healing wound, active ulcer, or untreated bone fracture