A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)

Eligibility Criteria

• * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
• * Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of
• * Liver Diseases criteria in cirrhotic patients
• * Child-Pugh class A within 7 days prior to randomization
• * Disease that is not amenable to curative surgical and/or locoregional therapies
• * No prior systemic treatment for HCC
• * Life expectancy \>= 3 months
• * Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
• * Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
• * Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment
• * Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV)
• * Negative HIV test at screening
• * For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm
• * ECOG Performance Status of 0, 1, or 2
• * Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
• * Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)
• * Total bilirubin ≤ 1.5 X ULN in the absence of Gilbert's disease (≤ 3.0 X ULN if Gilbert's disease)
• * AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases present)
• * Prior treatment with CD137 agonists or immune checkpoint blockade therapies or inhibitors targeting HIF2a
• * Treatment with investigational therapy within 28 days prior to initiation of study
• * Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure
• * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding
• * Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study
• * AEs from prior anti-cancer therapy that have not resolved to Grade \<= 1 or better, with the exception of alopecia of any grade
• * Inadequately controlled hypertension
• * History of hypertensive crisis or hypertensive encephalopathy
• * Significant vascular disease
• * History of hemoptysis within 1 month prior to initiation of study
• * Evidence of bleeding diathesis or significant coagulopathy
• * Current or recent use of aspirin (\>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol
• * Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose
• * Core biopsy or other minor surgical procedure within 3 days prior to initiation of study
• * History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction
• * Evidence of abdominal free air not explained by paracentesis or recent surgery
• * Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture
• * Grade \>=2 proteinuria
• * Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume
• * History of clinically significant intra-abdominal inflammatory process
• * Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study
• * Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure
• * Chronic daily treatment with NSAID
• * Eligible only for control arm
• * Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• * History of hepatic encephalopathy
• * Moderate or severe ascites
• * HBV and HCV coinfection
• * Symptomatic, untreated, or actively progressing CNS metastases
• * History of leptomeningeal disease
• * Uncontrolled tumor-related pain
• * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• * Uncontrolled or symptomatic hypercalcemia
• * Active or history of autoimmune disease or immune deficiency
• * History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• * Active TB
• * Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina
• * Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study
• * History of malignancy other than HCC within 5 years prior to screening
• * Severe infection within 4 weeks prior to initiation of study
• * Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study
• * Prior allogeneic stem cell or solid organ transplantation
• * Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• * History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• * Known allergy or hypersensitivity to any of the study drugs or any of their excipients
• * Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study
• * Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
• * Grade \>= 3 hemorrhage or bleeding event within 8 weeks prior to initiation of study treatment
• * Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent