A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma [IMbrave150]

The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A
(experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib

Inclusion Criteria:

- Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)

- No prior systemic therapy for HCC. Previous use of herbal therapies/traditional
Chinese medicines with anti-cancer activity included in the label is allowed, provided
that these medications are discontinued prior to randomization.

- At least one measurable untreated lesion

- ECOG Performance Status of 0 or 1

- Adequate hematologic and end-organ function

- For women of childbearing potential: agreement to remain abstinent

- For men: agreement to remain abstinent

- Child-Pugh class A

Exclusion Criteria:

- History of leptomeningeal disease

- Active or history of autoimmune disease or immune deficiency

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography scan

- Known active tuberculosis

- History of malignancy other than HCC within 5 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death

- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
or within at least 5 months after the last dose of atezolizumab, 6 months after the
last dose of bevacizumab, or 1 month after the last dose of sorafenib

- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
high-risk for bleeding

- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
to initiation of study treatment.

- Moderate or severe ascites

- History of hepatic encephalopathy

- Co-infection of HBV and HCV

- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures

- Uncontrolled or symptomatic hypercalcemia

- Treatment with systemic immunostimulatory agents

- Inadequately controlled arterial hypertension

- Prior history of hypertensive crisis or hypertensive encephalopathy

- Evidence of bleeding diathesis or significant coagulopathy

- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction
including sub-occlusive disease related to the underlying disease or requirement for
routine parenteral hydration

- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture

- Metastatic disease that involves major airways or blood vessels, or centrally located
mediastinal tumor masses

- Local therapy to liver within 28 days prior to initiation of study treatment or
non-recovery from side effects of any such procedure

- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)