Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)

Inclusion Criteria:

• Is male or female and ≥18 years of age at the time of signing the informed consent

• Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, orcytology

• Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B diseasenot amenable to locoregional therapy or refractory to locoregional therapy, and notamenable to a curative treatment approach

• Has a Child-Pugh class A liver score

• Has a predicted life expectancy of >3 months

• Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 as confirmed by BICR

• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1

• Participants with hepatitis B will be eligible as long as their virus is wellcontrolled

Exclusion Criteria:

• Has had esophageal or gastric variceal bleeding within the last 6 months

• Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any othercondition that might affect the absorption of lenvatinib

• Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula

• Has clinically significant hemoptysis from any source or tumor bleeding within 2weeks prior to the first dose of study intervention

• Has significant cardiovascular impairment within 12 months of the first dose ofstudy intervention such as history of congestive heart failure greater than New YorkHeart Association (NYHA) Class II, unstable angina, myocardial infarction orcerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamicinstability

• Has had major surgery to the liver within 4 weeks prior to the first dose of studyintervention

• Has had a minor surgery (ie, simple excision) within 7 days prior to the first doseof study intervention

• Has serious non-healing wound, ulcer, or bone fracture

• Has received any systemic chemotherapy for HCC or chemotherapy for any malignancy inthe past 3 years

• Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1),anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell deathligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory orco-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, or CD137)

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapyor any other form of immunosuppressive therapy within 7 days prior the first dose ofstudy intervention

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years with the exceptions of basal cell carcinoma of theskin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breastcarcinoma, cervical cancer in situ) that has undergone potentially curative therapy

• Has a known history of, or any evidence of, central nervous system (CNS) metastasesand/or carcinomatous meningitis as assessed by local site investigator

• Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of theirexcipients

• Has an active autoimmune disease that has required systemic treatment in past 2years

• Has a history of (non-infectious) pneumonitis that required steroids or has currentpneumonitis

• Has urine protein ≥1 grams/24 hours

• Prolongation of corrected QT (QTc) interval to >480 milliseconds (corrected byFridericia Formula)

• Has left ventricular ejection fraction (LVEF) below the institutional normal rangeas determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)

• Has an active infection requiring systemic therapy with the exceptions of hepatitisB virus (HBV) or hepatitis C virus (HCV)

• Has a known history of human immunodeficiency virus (HIV) infection

• Has known active tuberculosis (Bacillus tuberculosis)

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with theparticipant's participation for the full duration of the study, or is not in thebest interest of the participant to participate, in the opinion of the treatinginvestigator

• Has a known psychiatric or substance abuse disorder that would interfere with theparticipant's ability to cooperate with the requirements of the study

• Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of study intervention

• Has had an allogenic tissue/solid organ transplant