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

Inclusion Criteria

• Inclusion Criteria: Stage 1 - 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 Stage 1 and Stage 2 - 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 Stage 2 - 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) NKT2152-Containing Arm: - 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) Exclusion Criteria: Stage 1 - 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 Stage 1 and 2 - 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