• Male or female, 18 years of age or older

• Confirmed diagnosis of HCC by either:

∙ Histologically or cytologically documented HCC based on pathology report or Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria

• Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach

• Child-Pugh class A or ≤ 7 class B liver score (no hepatic encephalopathy) within 7 days of first dose of the investigational product(s)

• Disease progression, intolerance or contraindication to at least one line of systemic therapy for advanced HCC Prior treatment with cabozantinib or lenvatinib is allowed in the combination dose escalation and expansion parts of the study.

• Measurable disease as defined by RECIST 1.1 with spiral computerized tomography (CT) scan or magnetic resonance imaging (MRI). Lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if progression has been demonstrated in such lesions.

• Willingness and ability to provide tumor biopsies during screening and while on treatment.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of the investigational product(s)

• Patients must have organ and marrow function as defined below within 7 days of the first dose of the investigational product(s):

‣ Absolute neutrophil count (ANC) ≥ 1.2 x 109/L

⁃ Platelets ≥ 60 x 10\^9/L; no transfusion within 7 days prior to assessment

⁃ Hemoglobin ≥ 9 g/dL (red blood cell transfusion or growth factors support is not allowed in the 14 days prior to the screening laboratory assessment)

⁃ Total bilirubin ≤ ULN

⁃ AST and ALT ≤ 5 x ULN

⁃ Renal Function : Estimated creatinine clearance (CrCl) ≥ 50 mL/min by the Cockcroft-Gault equation using actual body weight, or Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min/1.73m2 by CKD-EPI Creatinine Equation, or Measured creatinine clearance ≥ 50 mL/min

⁃ Albumin ≥ 2.8 g/dL

⁃ International normalized ratio (INR) ≤ 1.7, unless the patient is receiving anticoagulant therapy as long as the patient is within therapeutic range of intended use of anticoagulants

• Washout period prior to Day 1 of Cycle 1:

‣ At least 21 days from the last dose of prior systemic anticancer treatment

⁃ At least 14 days from palliative radiotherapy (≤ 10 fractions or ≤30 gray \[Gy\] total dose or at least 28 days from radiotherapy \> 30 Gy) to extrahepatic tumor lesions

⁃ At least 28 days from local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation)

• Grade ≤ 1 toxicity due to any previous cancer therapy according to the NCI-CTCAE, v.5. Grade 2 is allowed in case of alopecia and/or peripheral sensory neuropathy.

• Participants with past HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention and HCV viral load must be below the limit of quantification.

• Participants with controlled HBV will be eligible if they meet the following criteria:

‣ Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of study drug. Patients on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention.

⁃ Patients who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis.

⁃ Patients must have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.