A Trial of Lenvatinib Plus Pembrolizumab in Subjects With Hepatocellular Carcinoma

Inclusion Criteria:

- Confirmed diagnosis of hepatocellular carcinoma (HCC)

- HCC for which no other appropriate therapy is available. Note: Expansion Part: No
prior systemic therapy for advanced/unresectable HCC

- Stage B (not applicable for transarterial chemoembolization [TACE]), or stage C based
on Barcelona Clinic Liver Cancer (BCLC) staging system

- At least 1 measurable target lesion according to modified Response Evaluation Criteria
in Solid Tumors (mRECIST)

- Child-Pugh score A

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1

- Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within normal
limits. (control by thyroid replacement therapy is acceptable.) Participants with T3,
free T3 or free T4 abnormalities at screening who are asymptomatic can be eligible

- Adequately controlled blood pressure

- Adequate renal function

- Adequate bone marrow function

- Adequate blood coagulation function

- Adequate liver function

- Males or females age ≥ 18 years at the time of informed consent

- Voluntary agreement to provide written informed consent and the willingness and
ability to comply with all aspects of the protocol

Exclusion Criteria:

- Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

- Any current brain or subdural metastases

- 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

- Any medical or other condition which, in the opinion of the investigator, would
preclude participation in a clinical trial

- Active infection (any infection requiring systemic treatment). Hepatitis B or C
[HBV/HCV] is allowed

- Participants with CNS metastases are not eligible, unless they have completed local
therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery) and have
discontinued the use of corticosteroids for this indication for at least 4 weeks
before starting treatment in this study. Any signs (eg, radiologic) or symptoms of
brain metastases must be stable for at least 4 weeks before starting study treatment