Purpose

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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Lenvatinib plus Pembrolizumab plus TACE
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).
  • Drug: Lenvatinib
    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) via oral capsules once a day during each 21-day cycle.
    Other names:
    • MK-7902
    • E7080
    • LENVIMA®
  • Biological: Pembrolizumab
    Administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W).
    Other names:
    • MK-3475
    • KEYTRUDA®
  • Procedure: TACE
    Conducted as a background procedure of chemotherapeutic and embolic agent(s).
Active Comparator
Oral Placebo plus IV Placebo plus TACE
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).
  • Drug: Oral Placebo
    Lenvatinib-matching placebo administered via oral capsules once a day during each 21-day cycle.
  • Drug: IV Placebo
    Pembrolizumab-matching placebo administered via IV infusion once every 6 weeks (Q6W).
  • Procedure: TACE
    Conducted as a background procedure of chemotherapeutic and embolic agent(s).

More Details

Status
Active, not recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.