Multinational Phase II Trial to Compare Safety and Efficacy of SIRT (Y-90 Resin Microspheres) Followed by Atezolizumab Plus Bevacizumab, vs SIRT (SIRT-Y90) Followed by Placebo in Locally Advanced HCC Patients

Patients must fulfill all of the following criteria to be eligible for this study:

Unequivocal diagnosis of HCC (AASLD 2010 diagnostic criteria or histology) that is locally advanced without extra-hepatic metastases but with significant tumor burden, i.e.,

Tumor confined to the liver that is beyond the up-to-7 criteria, and/orTumor with vascular invasion VP 1-3 and/or Vv 1-2 (at the discretion of site investigator) Both local and central assessments are required at screening, prior to any study treatment. Sites are required to send all CT/MRI images for central imaging review. The central assessment result will be made known to sites and will take precedence in determining a patient's study eligibility in case of a discrepancy between local and central review. Aged 21 years old and above of either gender.

Patient eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (Tc-99m MAA) scan on SPECT/CT or planar imaging with all of the following criteria prior to each SIRT-Y90 treatment:

Lung shunting <20% on SPECT/CT or planar imagingLung dose limit of <25Gy for single treatment or <30Gy for cumulative treatment (second delivery within 4-6 weeks) No prior radiation to the liver. No prior systemic adjuvant or neoadjuvant therapy for HCC. Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan or MRI.

Negative HIV test at screening, with the following exception - patients with a positive HIV test at screening are eligible provided they fulfil all of the following criteria:

Are stable on anti-retroviral therapyHave a CD4 count ≥ 200/μL Have an undetectable viral load Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests.

Patients with active HBV: HBV DNA <500 IU/mL, initiation of anti-HBV treatment at least 14 days prior to randomization, and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir).

For patients with HBV DNA ≥ 500 IU/mL during screening, anti-HBV treatment will be initiated and HBV DNA levels will be re-assessed prior to randomization.

ECOG performance status 0 - 1.Child-Pugh A (up to 6 points).

Adequate hematological, renal, and hepatic function as follows:

Lymphocyte count ≥ 0.5 x 10**9/L (500/μL)Platelets ≥75,000/μL without transfusion Hemoglobin >9.5 g/dL (Patients may be transfused to meet this criterion.) Serum bilirubin ≤ 3 x ULN For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 2.0 x ULN ALP ≤5×institutional upper limit of normal AST and ALT ≤5×institutional upper limit of normal Albumin ≥2.8 g/dL Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula) Absolute Neutrophil Count ≥1.5×10**9/L without granulocyte colony-stimulating factor support

Urine dipstick for proteinuria <2+ at screening

Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1g of protein in 24 hoursLife expectancy of at least 3 months without any active treatment. Suitable for protocol treatment as determined by clinical assessment undertaken by the site investigator.

Performance of an esophagogastroduodenoscopy (EGD) within 6 months prior to randomization as part of pre-procedure work-up or during screening, and assessment and complete treatment of varices of all sizes per local standard of care prior to randomization.

Patients with varices should be re-assessed prior to randomization to ensure complete treatment of varices of all sizes per local standard of care.

Willing, able and mentally competent to provide written informed consent prior to any testing undertaken for this study protocol, including screening tests and evaluations that are not considered to be part of the patient's routine care.Female patients must be either postmenopausal or, if premenopausal, must have a negative pregnancy test and agree to use two forms of contraception if sexually active during the treatment period, for at least 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab. Male patients must be surgically sterile, or if sexually active and having a pre-menopausal female partner, they must be using an acceptable form of contraception during the treatment period and for 6 months after the last dose of bevacizumab.