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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04246177




Registration number
NCT04246177
Ethics application status
Date submitted
27/01/2020
Date registered
29/01/2020
Date last updated
13/09/2023

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
MK-7902-012
Secondary ID [2] 0 0
7902-012
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib
Treatment: Other - Pembrolizumab
Treatment: Drugs - Oral Placebo
Treatment: Drugs - IV Placebo
Treatment: Surgery - TACE

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).

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).


Treatment: Drugs: 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.

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

Treatment: Drugs: Oral Placebo
Lenvatinib-matching placebo administered via oral capsules once a day during each 21-day cycle.

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

Treatment: Surgery: TACE
Conducted as a background procedure of chemotherapeutic and embolic agent(s).
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to ~43 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~95 months
Secondary outcome [1] 0 0
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [1] 0 0
Up to ~43 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR) per mRECIST
Timepoint [2] 0 0
Up to ~95 months
Secondary outcome [3] 0 0
Disease Control Rate (DCR) per mRECIST
Timepoint [3] 0 0
Up to ~95 months
Secondary outcome [4] 0 0
Duration of Response (DOR) per mRECIST
Timepoint [4] 0 0
Up to ~95 months
Secondary outcome [5] 0 0
Time to Progression (TTP) per mRECIST
Timepoint [5] 0 0
Up to ~95 months
Secondary outcome [6] 0 0
Percentage of Participants Who Experience At Least One Adverse Event (AE)
Timepoint [6] 0 0
Up to ~95 months
Secondary outcome [7] 0 0
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)
Timepoint [7] 0 0
Up to ~95 months
Secondary outcome [8] 0 0
Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI)
Timepoint [8] 0 0
Up to ~95 months
Secondary outcome [9] 0 0
Percentage of Participants Who Discontinue Study Drug Due to an AE
Timepoint [9] 0 0
Up to ~95 months
Secondary outcome [10] 0 0
ORR per RESCIST 1.1
Timepoint [10] 0 0
Up to ~95 months
Secondary outcome [11] 0 0
DCR per RECIST 1.1
Timepoint [11] 0 0
Up to ~95 months
Secondary outcome [12] 0 0
DOR per RECIST 1.1
Timepoint [12] 0 0
Up to ~95 months
Secondary outcome [13] 0 0
TTP per RECIST 1.1
Timepoint [13] 0 0
Up to ~95 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/05/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
450
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
St George Hospital ( Site 0005) - Kogarah
Recruitment hospital [2] 0 0
Westmead Hospital-Gastroenterology & Hepatology ( Site 0009) - Westmead
Recruitment hospital [3] 0 0
Princess Alexandra Hospital ( Site 0006) - Brisbane
Recruitment hospital [4] 0 0
Austin Health ( Site 0008) - Heidelberg
Recruitment hospital [5] 0 0
Alfred Health ( Site 0004) - Melbourne
Recruitment hospital [6] 0 0
Royal Perth Hospital ( Site 0002) - Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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Arizona
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California
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Connecticut
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North Carolina
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China
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China
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China
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China
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China
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China
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China
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Hessen
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Shatin
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Pusan-Kwangyokshi
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Korea, Republic of
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Taegu-Kwangyokshi
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Korea, Republic of
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Seoul
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Limburg
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Noord-Holland
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Utrecht
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New Zealand
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Auckland
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Norway
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Oslo
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Portugal
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Puerto Rico
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Ponce
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Puerto Rico
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San Juan
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Spain
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Madrid
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Spain
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Valenciana, Comunitat
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Spain
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Sevilla
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Krung Thep Maha Nakhon
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Konya
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Turkey
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Malatya
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Ukraine
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Kharkivska Oblast
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Ukraine
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Kyivska Oblast
Country [136] 0 0
United Kingdom
State/province [136] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/study/NCT04246177
Trial related presentations / publications
Verset G, Borbath I, Karwal M, Verslype C, Van Vlierberghe H, Kardosh A, Zagonel V, Stal P, Sarker D, Palmer DH, Vogel A, Edeline J, Cattan S, Kudo M, Cheng AL, Ogasawara S, Daniele B, Chan SL, Knox JJ, Qin S, Siegel AB, Chisamore M, Hatogai K, Wang A, Finn RS, Zhu AX. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Clin Cancer Res. 2022 Jun 13;28(12):2547-2554. doi: 10.1158/1078-0432.CCR-21-3807.
Llovet JM, Vogel A, Madoff DC, Finn RS, Ogasawara S, Ren Z, Mody K, Li JJ, Siegel AB, Dubrovsky L, Kudo M. Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment. Cardiovasc Intervent Radiol. 2022 Apr;45(4):405-412. doi: 10.1007/s00270-021-03031-9. Epub 2022 Feb 4.
Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.
Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1:137-149. doi: 10.1002/hep.31424. Epub 2020 Nov 6. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04246177