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Completed

NCT Number: NCT04246177

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)

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).

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Key information

Conditions

Carcinoma, Hepatocellular Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Parkinson Disease 4, Autosomal Dominant Lewy Body

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

St George Hospital ( Site 0005), Kogarah, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Lenvatinib

Drug

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®

Pembrolizumab

Biological

Administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W).

Other names: MK-3475, KEYTRUDA®

oral placebo

Drug

Lenvatinib-matching placebo administered via oral capsules once a day during each 21-day cycle.

IV Placebo

Drug

Pembrolizumab-matching placebo administered via IV infusion once every 6 weeks (Q6W).

TACE

Procedure

Conducted as a background procedure of chemotherapeutic and embolic agent(s).

Primary outcomes

  1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    Time frame: Up to ~43 months

    PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR).

  2. Overall Survival (OS)

    Time frame: Up to ~95 months

    OS is defined as the time from randomization to death due to any cause.

Secondary outcomes

  1. PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

    Time frame: Up to ~43 months

    PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.

  2. Objective Response Rate (ORR) per mRECIST

    Time frame: Up to ~95 months

    ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions). Responses are according to mRECIST as assessed by BICR.

  3. Disease Control Rate (DCR) per mRECIST

    Time frame: Up to ~95 months

    DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of any intratumoral arterial enhancement in all target lesions), PR (at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions), or stable disease (SD). Responses are according to mRECIST as assessed by BICR.

  4. Duration of Response (DOR) per mRECIST

    Time frame: Up to ~95 months

    DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of any intratumoral arterial enhancement in all target lesions) or PR (at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.

  5. Time to Progression (TTP) per mRECIST

    Time frame: Up to ~95 months

    TTP is defined as the time from randomization to the first documented disease progression. Responses are according to mRECIST as assessed by BICR.

  6. Percentage of Participants Who Experience At Least One Adverse Event (AE)

    Time frame: Up to ~95 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.

  7. Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)

    Time frame: Up to ~95 months

    An SAE is an AE that results in death, is life threatening, requires or prolongs a hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants who experience at least one SAE will be reported.

  8. Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI)

    Time frame: Up to ~95 months

    Percentage of participants with Hepatic ECIs not due to disease progression or TACE as assessed by the investigator will be reported.

  9. Percentage of Participants Who Discontinue Study Drug Due to an AE

    Time frame: Up to ~95 months

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug due to an AE will be reported.

  10. ORR per RESCIST 1.1

    Time frame: Up to ~95 months

    ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by BICR.

  11. DCR per RECIST 1.1

    Time frame: Up to ~95 months

    DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), or SD. Responses are according to RECIST 1.1 as assessed by BICR.

  12. DOR per RECIST 1.1

    Time frame: Up to ~95 months

    DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR.

  13. TTP per RECIST 1.1

    Time frame: Up to ~95 months

    TTP is defined as the time from randomization to the first documented disease progression. Responses are according to RECIST 1.1 as assessed by BICR.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Collaborators

  • Eisai Inc.

Registry information

Official study title

A Phase 3 Multicenter, Randomized, Double-blinded, Active-controlled, Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (LEAP-012)

Important dates

Study start
2020
Primary completion
2025
Study completion
2026
First posted
Jan 29, 2020
Registry last updated
May 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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