Clinical Research Directory

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