Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (MK-7902-012/E7080-G000-318/LEAP-012)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: Carcinoma, Hepatocellular

Treatments: Drug: Oral Placebo; Drug: Lenvatinib; Biological: Pembrolizumab; Procedure: TACE; Drug: IV Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04246177

7902-012

E7080-G000-318 (Other Identifier)

LEAP-012 (Other Identifier)

2019-002345-37 (EudraCT Number)

205286 (Registry Identifier)

MK-7902-012 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of lenvatinib and pembrolizumab in combination with TACE versus TACE plus oral and intravenous (IV) placebos in participants with incurable, non-metastatic hepatocellular carcinoma (HCC). The primary hypotheses are that pembrolizumab plus lenvatinib in combination with TACE is superior to placebo plus TACE with respect to progression-free survival (PFS) and overall survival (OS).

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a diagnosis of HCC confirmed by radiology, histology, or cytology
• Has HCC localized to the liver and not amenable to curative treatment
• Participants with Hepatitis C virus (HCV) are eligible if treatment was completed at least 1 month prior to starting study intervention
• Participants with Hepatitis B virus (HBV) are eligible
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function

Exclusion criteria

• Is currently a candidate for liver transplantation
• Has had gastric bleeding within the last 6 months
• Has ascites that is not controlled with medication
• Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as congestive heart failure
• Has a serious nonhealing wound, ulcer, or bone fracture
• Has received locoregional therapy to existing liver lesions

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups

Lenvatinib plus Pembrolizumab plus TACE

Experimental group

Description:

Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years \[\~35 cycles\] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).

Treatment:

Biological: Pembrolizumab

Procedure: TACE

Drug: Lenvatinib

Oral Placebo plus IV Placebo plus TACE

Active Comparator group

Description:

Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (\~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).

Treatment:

Drug: IV Placebo

Drug: Oral Placebo

Procedure: TACE