Sequential or Up-front Triple Treatment With Durvalumab, Tremelimumab and Bevacizumab for Non-resectable Hepatocellular Carcinoma (HCC) Patients (MONTBLANC)

KEY INCLUSION CRITERIA Age ≥18 years at the time of study entry Confirmed HCC based on histopathological findings from tumor tissues. Must not have received prior systemic therapy for HCC. Not eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan for the current study. Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C Child-Pugh Score class A ECOG performance status of 0 or 1 at enrollment At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria. Adequate organ and marrow function KEY EXCLUSION CRITERIA Previous study drug(s) assignment in the present study. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug(s). Major surgical procedure or significant traumatic injury within 28 days prior to the first dose of study drug(s), abdominal surgery, abdominal interventions, or significant abdominal traumatic injury within 60 days prior to randomization History of allogeneic organ transplantation (eg, liver transplant). History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy Clinically meaningful ascites Patients with main portal vein thrombosis (i.e., thrombosis in the main trunk of the portal vein, with or without blood flow) on baseline imaging. Patient currently exhibits symptomatic or uncontrolled hypertension Active or prior documented autoimmune or inflammatory disorders, diverticulitis. Patients without active disease in the last 5 years are excluded unless discussed with the Study Physician and considered appropriate for study participation. Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV). History of another primary malignancy except for the exceptions defined by the study protocol. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. History of active primary immunodeficiency. Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug(s). Note: Patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s). Major gastrointestinal bleeding within 4 weeks prior to randomization. Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding. 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 prior to randomization do not need to repeat the procedure. Those who have received banding and/or sclerotherapy and with no bleeding event within the prior 6 months are eligible provided that a re-endoscopy is performed and that varices remained obliterated, minimal or Grade I Significant vascular disease including aortic aneurysm requiring surgical repair or peripheral arterial thrombosis with 6 months prior to randomization History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization. Evidence of bleeding diathesis or significant coagulopathy Severe, nonhealing or dehisced wound, active ulcer, or untreated bone fracture Current or recent (within 10 days of randomization) use of acetylsalicyclic acid (=> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol Current or recent (within 10 days prior to randomization) use of fulldose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose. Prophylactic use of low molecularweight heparin is allowed. Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab plus tremelimumab combination therapy or bevacizumab therapy Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.