• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.

• Age ≥18 years at the time of informed consent.

• Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.

• Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy. No biopsy is required for participants in Cohort C.

• Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST Version 1.1.

• Able to swallow tablets.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Has adequate hematologic and organ function as defined by the following local laboratory values at screening:

‣ Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L (1500/μL) without granulocyte colony-stimulating factor support.

⁃ Lymphocyte count ≥0.5 × 10\^9/L (500/μL).

⁃ Platelet count ≥75 × 10\^9/L (75,000/μL) without transfusion.

⁃ Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.

⁃ Serum albumin ≥28 g/L (2.8 g/dL).

⁃ AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).

⁃ Serum bilirubin ≤2 mg/dL.

⁃ Adequate renal function defined as either:

• creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or

∙ 24-hour urine collection.

• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.

⁃ Child-Pugh class A or B7 within 7 days prior to enrollment.

⁃ Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must:

∙ Have a negative serum pregnancy test at screening.

‣ Not be breastfeeding or lactating.

‣ Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices, or permanent sterilization.

⁃ Males must:

∙ Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.

‣ Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.

‣ Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices in female partners, or permanent sterilization.

⁃ Cohort A:

⁃ In addition to the general inclusion criteria, participants enrolled in Cohort A must have demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy.

⁃ Cohort B:

⁃ In addition to the general inclusion criteria, participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy. Participants may have received no more than one line of prior systemic therapy.

⁃ Agree to use contraception as specified in the general inclusion criteria for at least 4 months following the last dose of pembrolizumab in accordance with the approved prescribing information.

⁃ Cohort C:

⁃ In addition to the general inclusion criteria, participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.

⁃ Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.

⁃ Agree to use contraception as specified in the general inclusion criteria for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing information.