A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma

Eisai

Status and phase: Completed; Phase 1

Conditions: Hepatocellular Carcinoma

Treatments: Drug: pembrolizumab (200 mg); Drug: lenvatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03006926

KEYNOTE 524 (Other Identifier)

E7080-J081-116

2018-000522-55 (EudraCT Number)

Details and patient eligibility

About

This is an open-label Phase 1b study designed to evaluate the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with hepatocellular carcinoma (HCC). The study will evaluate objective response rate and duration of response by modified Response Evaluation Criteria In Solid Tumors (mRECIST) for HCC and Response Evaluation Criteria In Solid Tumors (RECIST 1.1) based on independent imaging review (IIR).

Enrollment: 104 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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
• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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104 participants in 1 patient group

lenvatinib 8 or 12 mg plus pembrolizumab 200 mg

Experimental group

Description:

Participants will receive oral lenvatinib at a starting dose of 8 or 12 milligrams (mg) once a day (QD) in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle. The starting dose of lenvatinib will be based on Baseline body weight. Participants weighing greater than or equal to 60 kilograms (kg) will receive 12 mg QD; participants weighing less than 60 kg will receive 8 mg QD.

Treatment:

Drug: pembrolizumab (200 mg)

Drug: lenvatinib