A Study to Assess the Safety and Efficacy of Lenvatinib as First-line Treatment in Participants With Unresectable HCC

Inclusion Criteria:

1. Males or females of \>=18 years of age
2. Participant or their legally acceptable representative (LAR) is willing to sign written informed consent for participation in the study and ready to comply with the study procedures and schedule
3. Must have a confirmed diagnosis of unresectable HCC with one of the following criteria:

   * Histologically or cytologically confirmed diagnosis of HCC
   * Clinically confirmed diagnosis of HCC according to the American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any aetiology or with chronic hepatitis B or C infection criteria
4. At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:

   * Hepatic lesion:

     * The lesion can be accurately measured in at least one dimension as \>=1.0 centimeter (cm)
     * The lesion is suitable for repeat measurement
   * Non-hepatic lesion:

     * Lymph node (LN) lesion that measures at least one dimension as \>=1.5 cm in the short axis, except for porta hepatis LN that measures \>=2.0 cm in the short axis
     * Non-nodal lesion that measures \>=1.0 cm in the longest diameter
   * Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion
5. Participants are categorized to Stage B (not applicable for transarterial chemoembolization \[TACE\]) or Stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
6. Has adequate bone marrow function, defined as:

   * Absolute neutrophil count (ANC) \>= 1.5\*10\^9 per liter (/L)
   * Haemoglobin \>=8.5 gram per deciliter (g/dL)
   * Platelet count \>=75\*10\^9/L
7. Adequate liver function based on liver function tests, defined as:

   * Albumin \>=2.8 g/dL
   * Bilirubin less than or equal to \<=3.0 milligram per deciliter (mg/dL)
   * Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) \<=5\*the upper limit of normal (ULN)
8. Adequate blood coagulation function, defined as international normalized ratio (INR) \<=2.3
9. Adequate renal function, defined as \>30 milliliter per minute (ml/min) calculated as per the Cockcroft and Gault formula
10. Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications, defined as BP \<=150/90 millimeter of mercury (mmHg) at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1
11. Adequate pancreatic function, defined as amylase and lipase \<=1.5\*ULN
12. With a Child-Pugh score A
13. With Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
14. With life expectancy of \>=12 weeks from the start of study treatment, as per Investigator's judgement.

Exclusion Criteria:

1. With imaging findings for HCC corresponding to any of the following:

   * HCC with \>=50% liver occupation
   * Clear invasion into the bile duct
   * Portal vein invasion at the main portal branch (Vp4)
2. Who have received any systemic chemotherapy, including sorafenib, or immunotherapy, or any systemic investigational anticancer agents for advanced/unresectable HCC
3. Who have received any anticancer therapy (including surgery, percutaneous ethanol injection, radio frequency ablation, transarterial \[chemo\] embolization, hepatic intra-arterial chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production, example granulocyte colony-stimulating factor \[G-CSF\]) within 28 days prior to enrolment
4. Who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility
5. With significant cardiovascular impairment including but not limited to the history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within previous 6 months, or cardiac arrhythmia requiring medical treatment at the time of screening
6. With prolongation of corrected QT (QTc) interval to \>480 millisecond (ms)
7. With gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the Investigator
8. Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
9. Having a gastrointestinal bleeding event or active haemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to enrollment
10. With gastric or oesophageal varices that may require treatment
11. With any other active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months prior to enrolment
12. Any history of, or concurrent, brain or subdural metastases
13. Having \>1 + proteinuria on urine dipstick testing will undergo 24 hour (h) urine collection for quantitative assessment of proteinuria. Patients with urine protein \>=1 gram per 24 hour (g/24 h) will be excluded
14. With arterial-portal venous shunt or arterial-venous shunt preventing a proper diagnosis of the tumour
15. Any medical or other condition that in the opinion of the Investigator would preclude the participant's participation in the study.
16. With known intolerance to lenvatinib (or any of the excipients)
17. With positive human immunodeficiency virus (HIV) or active infection requiring treatment (except for hepatitis virus)
18. Who cannot be evaluated by either triphasic liver computed tomography (CT) or triphasic liver magnetic resonance imaging (MRI) because of allergy or other contraindication to both CT and MRI contrast agents
19. Have undergone major surgery within 3 weeks prior to the entry in the study or are scheduled for a surgery during the study period
20. Have already undergone a liver transplant
21. Female participants who are breastfeeding or pregnant at the time of enrolment in the study
22. Female participants of childbearing potential who, within 4 weeks prior to study enrolment, did not use a highly effective method of contraception or do not agree to use a highly effective method of contraception throughout the study period
23. Current abuse of alcohol; and current or past (last 12 months) abuse of drugs
24. Participation in a concurrent clinical trial or in another trial within the 6 months prior to this study enrolment