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)
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT04246177
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 450
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oral Placebo plus IV Placebo plus TACE Oral Placebo 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). Oral Placebo plus IV Placebo plus TACE IV Placebo 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). Lenvatinib plus Pembrolizumab plus TACE Pembrolizumab 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). Lenvatinib plus Pembrolizumab plus TACE 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). Oral Placebo plus IV Placebo plus TACE 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). Lenvatinib plus Pembrolizumab plus TACE Lenvatinib 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).
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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).
Overall Survival (OS) Up to ~95 months OS is defined as the time from randomization to death due to any cause.
- Secondary Outcome Measures
Name Time Method Time to Progression (TTP) per mRECIST 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.
ORR per RESCIST 1.1 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.
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE) 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.
DCR per RECIST 1.1 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.
DOR per RECIST 1.1 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.
TTP per RECIST 1.1 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.
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) 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.
Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI) 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.
Disease Control Rate (DCR) per mRECIST 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.
Duration of Response (DOR) per mRECIST 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.
Percentage of Participants Who Experience At Least One Adverse Event (AE) 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.
Percentage of Participants Who Discontinue Study Drug Due to an AE 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.
Objective Response Rate (ORR) per mRECIST 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.
Trial Locations
- Locations (205)
Arizona Oncology Associates PC- HOPE ( Site 0770)
🇺🇸Tucson, Arizona, United States
Scripps Clinic Torrey Pines ( Site 0714)
🇺🇸La Jolla, California, United States
USC Norris Comprehensive Cancer Center ( Site 0717)
🇺🇸Los Angeles, California, United States
UCLA Hematology/Oncology - Santa Monica ( Site 0720)
🇺🇸Los Angeles, California, United States
UC Irvine Health ( Site 0718)
🇺🇸Orange, California, United States
Yale Cancer Center ( Site 0724)
🇺🇸New Haven, Connecticut, United States
Tampa General Hospital ( Site 0764)
🇺🇸Tampa, Florida, United States
Mountain States Tumor Institute ( Site 0773)
🇺🇸Boise, Idaho, United States
University of Iowa Hospital and Clinics ( Site 0729)
🇺🇸Iowa City, Iowa, United States
University of Kansas Cancer Center ( Site 0731)
🇺🇸Westwood, Kansas, United States
Scroll for more (195 remaining)Arizona Oncology Associates PC- HOPE ( Site 0770)🇺🇸Tucson, Arizona, United States