- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03776136
Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) for Advanced Melanoma in Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1)-Exposed Participants (MK-7902-004/E7080-G000-225/LEAP-004)
October 16, 2023 updated by: Merck Sharp & Dohme LLC
A Multicenter, Open-label, Phase 2 Trial to Assess the Efficacy and Safety of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Melanoma Previously Exposed to an Anti-PD-1/L1 Agent (LEAP-004)
This study will evaluate the safety and efficacy of combination therapy of lenvatinib (E7080/MK-7902) and pembrolizumab following approximately 2 years of pembrolizumab therapy and approximately 2 years or more lenvatinib therapy in adult participants with unresectable or advanced melanoma who have been exposed to anti-PD-1/L1 agents approved for unresectable or metastatic melanoma.
No statistical hypothesis will be tested in this study.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
103
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Lismore, Australia, 2480
- Lismore Base Hospital ( Site 0153)
-
-
New South Wales
-
Wollstonecraft, New South Wales, Australia, 2065
- Melanoma Institute Australia ( Site 0152)
-
-
Queensland
-
Woolloongabba, Queensland, Australia, 4102
- Princess Alexandra Hospital ( Site 0154)
-
-
Victoria
-
Box Hill, Victoria, Australia, 3128
- Box Hill Hospital ( Site 0157)
-
-
Western Australia
-
Perth, Western Australia, Australia, 6150
- Fiona Stanley Hospital ( Site 0156)
-
-
-
-
Ontario
-
Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Research Institute ( Site 0654)
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Cancer Centre ( Site 0655)
-
-
Quebec
-
Montreal, Quebec, Canada, H4A 3J1
- McGill University Health Centre ( Site 0651)
-
Montreal, Quebec, Canada, H2X 3E4
- Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)
-
-
-
-
-
Barcelona, Spain, 08036
- Hospital Clinic i Provincial Barcelona ( Site 0001)
-
Madrid, Spain, 28007
- Hospital General Universitario Gregorio Maranon ( Site 0003)
-
Sevilla, Spain, 41009
- Hospital Universitario Virgen de la Macarena ( Site 0004)
-
Valencia, Spain, 46014
- Hospital General Universitario de Valencia ( Site 0002)
-
-
-
-
-
Goteborg, Sweden, 413 45
- Sahlgrenska Universitetssjukhuset ( Site 0052)
-
Lund, Sweden, 221 85
- Skanes Universitetssjukhus ( Site 0053)
-
Solna, Sweden, 171 64
- Karolinska Universitetssjukhuset ( Site 0051)
-
Umea, Sweden, 901 85
- Norrlands Universitetssjukhus ( Site 0056)
-
-
-
-
Arizona
-
Chandler, Arizona, United States, 85224
- Ironwood Cancer & Research Centers ( Site 0312)
-
-
California
-
Santa Monica, California, United States, 90404
- John Wayne Cancer Institute ( Site 0301)
-
-
Illinois
-
Park Ridge, Illinois, United States, 60068
- Advocate Medical Group-Park Ridge ( Site 0313)
-
-
Nebraska
-
Lincoln, Nebraska, United States, 68510
- Southeast Nebraska Cancer Center ( Site 0316)
-
-
Texas
-
Dallas, Texas, United States, 75246
- Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0317)
-
-
Virginia
-
Fairfax, Virginia, United States, 22031-4867
- Inova Schar Cancer Institute ( Site 0314)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Has histologically or cytologically confirmed melanoma
- Has unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8 that is not amenable to local therapy
- Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 as confirmed by BICR.
- Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
- Has submitted pre-trial imaging
- Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Has provided a baseline tumor biopsy
- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the Intervention
- Male participants must agree to use approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period
- Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention
- Has adequate organ function
Exclusion Criteria:
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
- Has a known additional malignancy that is progressing or requires active treatment
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has ocular melanoma
- Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody
- Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Has an active infection requiring systemic therapy
- Has known history of Human Immunodeficiency Virus (HIV) or HIV 1/2 antibodies
- Has known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (HCV RNA qualitative] is detected)
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- Has a history of active tuberculosis (Bacillus tuberculosis)
- Has presence of a gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
- Has had major surgery within 4 weeks prior to first dose of study interventions (adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility)
- Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- Has radiographic evidence of major blood vessel invasion/infiltration
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- Has clinically significant cardiovascular disease within 12 months from first dose of study drug, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
- Has received prior radiotherapy within 2 weeks of Cycle 1 Day 1 with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to Cycle 1 Day 1
- Has received a live vaccine within 30 days before the first dose of study treatment
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
- Has a history or has current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has had an allogeneic tissue/solid organ transplant
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: lenvatinib plus pembrolizumab
Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W).
Pembrolizumab will be administered for up to 35 cycles (approximately 24 months).
Lenvatinib will be administered until progressive disease or unacceptable toxicity.
|
Administered orally once a day during each 21-day cycle.
Other Names:
Administered as an IV infusion on Day 1 Q3W.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
Time Frame: Up to 3 years
|
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 [SOD] of target lesions, taking as reference the baseline SOD) per RECIST 1.1 as assessed by blinded independent central review (BICR).
RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
|
Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
Time Frame: Up to 3 years
|
PFS is defined as the time from the first day of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.
Responses are according to the RECIST 1.1 as assessed by BICR.
RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
|
Up to 3 years
|
Overall Survival (OS)
Time Frame: Up to 3 years
|
OS is defined as the time from the first day of study treatment to death due to any cause.
|
Up to 3 years
|
Duration of Response (DOR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
Time Frame: Up to 3 years
|
DOR is defined as the time from first documented evidence of CR or PR, per RECIST 1.1 as assessed by BICR, until disease progression or death due to any cause, whichever occurs first.
RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
|
Up to 3 years
|
Percentage of Participants Who Experience At Least One Adverse Event (AE)
Time Frame: Up to 3 years
|
An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
The percentage of participants who experience at least one AE will be reported.
|
Up to 3 years
|
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to 3 years
|
An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
The percentage of participants who discontinue study treatment due to an AE will be reported.
|
Up to 3 years
|
Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)
Time Frame: At designated time points on Day 1 and Day 15 of Cycle 1 (21-day cycle) and Day 1 of Cycle 2 (21-day cycle)
|
Blood samples will be obtained on Day 1 and Day 15 of Cycle 1 (21-day cycle) and Day 1 of Cycle 2 (21-day cycle) for pharmacokinetic (PK) analysis to determine the AUC of lenvatinib.
|
At designated time points on Day 1 and Day 15 of Cycle 1 (21-day cycle) and Day 1 of Cycle 2 (21-day cycle)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 30, 2019
Primary Completion (Actual)
October 11, 2023
Study Completion (Actual)
October 11, 2023
Study Registration Dates
First Submitted
December 13, 2018
First Submitted That Met QC Criteria
December 13, 2018
First Posted (Actual)
December 14, 2018
Study Record Updates
Last Update Posted (Actual)
October 17, 2023
Last Update Submitted That Met QC Criteria
October 16, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Immune Checkpoint Inhibitors
- Pembrolizumab
- Lenvatinib
Other Study ID Numbers
- 7902-004
- MK-7902-004 (Other Identifier: Merck Protocol Number)
- E7080-G000-225 (Other Identifier: Eisai Protocol Number)
- LEAP-004 (Other Grant/Funding Number: Merck)
- 2018-002518-10 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Melanoma
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma (Locally Advanced) | Stage IIC Melanoma (Locally Advanced) | Stage IV Melanoma (Limited, Resectable)United States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
-
Regeneron PharmaceuticalsBristol-Myers SquibbCompletedMelanoma | Metastatic Melanoma | Unresectable Melanoma | Advanced MelanomaUnited States
-
Regeneron PharmaceuticalsBristol-Myers SquibbActive, not recruitingMelanoma | Metastatic Melanoma | Unresectable Melanoma | Advanced MelanomaUnited States
-
MorphotekTerminatedMelanoma | Metastatic Melanoma | Advanced Melanoma | Malignant Metastatic MelanomaUnited States
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Metastatic Melanoma | Advanced Non-hematologic MalignanciesUnited States
-
University of Colorado, DenverMerck Sharp & Dohme LLCActive, not recruitingStage IV Melanoma | Advanced Melanoma | Stage III MelanomaUnited States
-
Azienda Ospedaliera di PerugiaNot yet recruitingAdvanced Melanoma | Early MelanomaItaly, Sweden, France, Germany, Netherlands, Poland, Spain
-
Cancer Trials IrelandCompletedMetastatic Melanoma | Advanced MelanomaIreland
-
Bristol-Myers SquibbCompletedMetastatic Melanoma | Advanced MelanomaUnited States, Netherlands, Spain
Clinical Trials on lenvatinib
-
Memorial Sloan Kettering Cancer CenterCompletedHead and Neck Cancer | Head and Neck Squamous Cell Carcinoma | Head and Neck Carcinoma | Cutaneous Squamous Cell CarcinomaUnited States
-
Fudan UniversityActive, not recruitingHepatocellular CarcinomaChina
-
Regina Elena Cancer InstituteUniversity of Pisa; University of Roma La Sapienza; University of Turin, Italy; Istituto Oncologico Veneto IRCCS and other collaboratorsRecruitingDifferentiated Thyroid Cancer | GenderItaly
-
Shandong New Time Pharmaceutical Co., LTDRecruitingHepatocellular CarcinomaChina
-
Cancer Institute and Hospital, Chinese Academy...Active, not recruitingHepatocellular Carcinoma | Radiotherapy | LenvatinibChina
-
CStone PharmaceuticalsActive, not recruitingHepatocellular CarcinomaSpain, China, United States, Poland, Italy, Taiwan
-
Shanghai Junshi Bioscience Co., Ltd.Active, not recruitingAdvanced Hepatocellular Carcinoma (HCC)Italy, Poland, Singapore, United States, China, Ukraine
-
Eisai Inc.Merck Sharp & Dohme LLCCompletedSolid TumorsUnited States, China, Belgium, Australia, Italy, Korea, Republic of, Germany, Netherlands, Poland, Romania, Thailand
-
Eisai Inc.CompletedThyroid CancerUnited States, Australia, France, Poland, United Kingdom, Italy
-
Shanghai Zhongshan HospitalActive, not recruitingCholangiocarcinoma, IntrahepaticChina