A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Hepatocellular Carcinoma

Inclusion Criteria: 1. Male or female Japanese participants 20 years of age or older on the day of consent. 2. Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted). 3. Measurable disease per response evaluation criteria in solid tumors (RECIST) 1.1 as determined by the investigator. 4. Participants who have disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation). 5. Participants who have received 1 or 2 prior anticancer therapies for advanced HCC. * Cohort A: participants who have received prior sorafenib. * Cohort B: participants who have not received prior sorafenib. Note: Additional prior systemic therapies used as adjuvant or local therapy are allowed. 6. Radiographic progression following prior systemic anticancer therapy for advanced HCC. 7. Recovery to =\<Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 from toxicities related to any prior treatments, unless the Adverse Events (AEs) are clinically nonsignificant and/or stable on supportive therapy. 8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and life expectancy of at least 3 months. 9. Child-Pugh Score of A. 10. Adequate organ and marrow function at Screening (within 10 days before Week 1 Day 1): 1. Absolute neutrophil count (ANC) \>=1,200/mm\^3. 2. Platelets \>=60,000/mm\^3. 3. Hemoglobin \>=8 g/dL. 4. Serum creatinine =\<1.5 × upper limit of normal (ULN) or calculated creatinine clearance \>=40 mL/min using the Cockroft-Gault equation. 5. Urine protein-to-creatinine ratio (UPCR) =\<1 mg/mg Cr. 6. Total bilirubin =\<2 mg/dL. 7. Serum albumin \>=2.8 g/dL. 8. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\<5.0 × ULN. 9. Hemoglobin A1c (HbA1c) =\<8% (if HbA1c results are unavailable \[eg, hemoglobin variant\], a fasting serum glucose =\<160 mg/dL). 11. Antiviral therapy per local standard of care if active hepatitis B virus (HBV) infection. 12. Female participants who: 1. Are postmenopausal (natural amenorrhea, not due to other medical reasons) for at least 1 year before the Screening visit, OR 2. Are surgically sterile, OR 3. If they are of childbearing potential, agree to practice 1 highly effective method of birth control with a condom, which is an effective barrier method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, OR 4. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, from the time of signing the informed consent through 4 months after the last dose of study drug. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\], condoms only, withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who: 5. Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug. If their partner are of childbearing potential, their female partner should use 1 highly effective method of birth control at the same time, OR 6. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, from the time of signing the informed consent through 4 months after the last dose of study drug. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\], condoms only, withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) 13. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. 14. Participant is willing and able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: 1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma. 2. Any type of anticancer agent within 14 days before the first day of study drug administration (Week 1 Day 1). 3. Radiation therapy within 28 days (14 days for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 42 days before Week 1 Day 1 (participant is excluded if there are any clinically relevant ongoing complications from prior radiation therapy). 4. Prior Cabozantinib treatment. 5. Treatment with any investigational products (excluding anticancer products approved in Japan) within 28 days before Week 1 Day 1. 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before Week 1 Day 1. Eligible participants must be without corticosteroid treatment at Week 1 Day 1. 7. Concomitant anticoagulation, with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Note: Low-dose aspirin for prophylactic use (per local applicable guidelines) and low-dose, low molecular weight heparins (LMWH) are permitted (LMWH has not been approved for the use for cardioprotection in Japan). Anticoagulation with therapeutic doses of LMWH is allowed in participants without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before Week 1 Day 1, and who have had no complications from a thromboembolic event or the anticoagulation regimen. 8. Participants who have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: 1. Cardiovascular disorders including * Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias. * Uncontrolled hypertension defined as sustained blood pressure (BP) \>150 mm Hg systolic, or \>100 mm Hg diastolic despite optimal antihypertensive treatment. * Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other ischemic event within 6 months before Week 1 Day 1. * Thromboembolic event within 3 months before Week 1 Day 1. * A left-ventricular ejection fraction =\<50%. 2. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: * Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction. * Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before Week 1 Day 1. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to Week 1 Day 1. 3. Major surgery within 2 months before Week 1 Day 1. Complete healing from major surgery must have occurred 1 month before Week 1 Day 1. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before Week 1 Day 1. Participants with clinically relevant complications from prior surgery are not eligible. 4. Cavitating pulmonary lesion(s) or endobronchial disease. 5. Lesion invading a major blood vessel including, but not limited to: inferior vena cava, pulmonary artery, or aorta. Participants with invasion or thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible. 6. Clinically significant bleeding risk including the following within 3 months before Week 1 Day 1: hematuria, hematemesis, hemoptysis of \>0.5 teaspoon (\>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors. 7. Other clinically significant disorders such as: * Active infection requiring systemic treatment. * Known infection with human immunodeficiency virus, or known acquired immunodeficiency syndrome -related illness. * Active hepatitis B and/or C. Participants with active hepatitis virus infection controlled with antiviral therapy are eligible. * Serious non-healing wound/ulcer/bone fracture. * Malabsorption syndrome. * Uncompensated/symptomatic hypothyroidism. * Requirement for hemodialysis or peritoneal dialysis. * History of solid organ transplantation. 9. Participants with untreated or incompletely treated varices with bleeding or high risk for bleeding. Participants treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months before Week 1 Day 1 are eligible. 10. Moderate or severe ascites. 11. Corrected QT interval calculated by the Fridericia formula (QTcF) \>500 msec within 14 days before Week 1 Day 1. Note: If the QTcF is \>500 msec in first electrocardiogram (ECG), a total of 3 ECGs each separated by at least 3 minutes should be performed within 30 minutes. If the average of these 3 consecutive results for QTcF is =\<500 msec, the participant meets eligibility in this regard. 12. Inability to swallow tablets. 13. Previously identified allergy or hypersensitivity to components of the study treatment formulations. 14. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period. Note: Female participants who are in the lactation period, even if they discontinue breastfeeding, will be excluded from the study. 15. Previously diagnosed with another malignancy and have any evidence of residual disease within 2 years before Week 1 Day 1. Note: Participants with superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy are not excluded. 16. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 17. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of Cabozantinib. 18. Use of strong cytochrome P450 (CYP) 3A inhibitors and CYP3A inducers within 14 days before Week 1 Day 1. 19. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.