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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)

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ClinicalTrials.gov Identifier: NCT03776136
Recruitment Status : Recruiting
First Posted : December 14, 2018
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Melanoma Drug: lenvatinib Biological: pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : January 30, 2019
Estimated Primary Completion Date : June 15, 2021
Estimated Study Completion Date : June 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

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.
Drug: lenvatinib
Administered orally once a day during each 21-day cycle.
Other Names:
  • MK-7902
  • E7080
  • LENVIMA™

Biological: pembrolizumab
Administered as an IV infusion on Day 1 Q3W.
Other Names:
  • MK-3475
  • Keytruda®




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 initial 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 95 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 95 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 that required steroids or current pneumonitis
  • 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 3 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03776136


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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United States, Arizona
Ironwood Cancer & Research Centers ( Site 0312) Recruiting
Chandler, Arizona, United States, 85224
Contact: Study Coordinator    480-324-5230      
United States, California
John Wayne Cancer Institute ( Site 0301) Recruiting
Santa Monica, California, United States, 90404
Contact: Study Coordinator    310-582-7455      
United States, Illinois
Advocate Medical Group-Park Ridge ( Site 0313) Recruiting
Park Ridge, Illinois, United States, 60068
Contact: Study Coordinator    847-410-0658      
United States, Nebraska
Southeast Nebraska Cancer Center ( Site 0316) Recruiting
Lincoln, Nebraska, United States, 68510
Contact: Study Coordinator    402-327-7363      
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0317) Recruiting
Dallas, Texas, United States, 75246
Contact: Study Coordinator    214-370-1942      
United States, Virginia
Inova Schar Cancer Institute ( Site 0314) Recruiting
Fairfax, Virginia, United States, 22031-4867
Contact: Study Coordinator    571-472-0237      
Australia, Queensland
Princess Alexandra Hospital ( Site 0154) Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Study Coordinator    +61731767825      
Australia, Victoria
Box Hill Hospital ( Site 0157) Recruiting
Box Hill, Victoria, Australia, 3128
Contact: Study Coordinator    +61300342255      
Australia, Western Australia
Fiona Stanley Hospital ( Site 0156) Recruiting
Perth, Western Australia, Australia, 6150
Contact: Study Coordinator    +61861526530      
Canada, Ontario
Sunnybrook Research Institute ( Site 0654) Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Study Coordinator    4164804757      
Princess Margaret Cancer Centre ( Site 0655) Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Study Coordinator    41694645013527      
Canada, Quebec
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652) Recruiting
Montreal, Quebec, Canada, H2X 3E4
Contact: Study Coordinator    514890800025307      
McGill University Health Centre ( Site 0651) Recruiting
Montreal, Quebec, Canada, H4A 3J1
Contact: Study Coordinator    51492419345033      
Spain
Hospital Clinic i Provincial Barcelona ( Site 0001) Recruiting
Barcelona, Spain, 08036
Contact: Study Coordinator    +34932275402      
Hospital General Universitario Gregorio Maranon ( Site 0003) Recruiting
Madrid, Spain, 28007
Contact: Study Coordinator    +34914269393      
Hospital Universitario Virgen de la Macarena ( Site 0004) Recruiting
Sevilla, Spain, 41009
Contact: Study Coordinator    +34955008000      
Hospital General Universitario de Valencia ( Site 0002) Recruiting
Valencia, Spain, 46014
Contact: Study Coordinator    +34963131800      
Sweden
Sahlgrenska Universitetssjukhuset ( Site 0052) Recruiting
Goteborg, Sweden, 413 45
Contact: Study Coordinator    +46313421000      
Skanes Universitetssjukhus ( Site 0053) Recruiting
Lund, Sweden, 221 85
Contact: Study Coordinator    +4646177520      
Karolinska Universitetssjukhuset ( Site 0051) Recruiting
Solna, Sweden, 171 64
Contact: Study Coordinator    +46851770214      
Norrlands Universitetssjukhus ( Site 0056) Recruiting
Umea, Sweden, 901 85
Contact: Study Coordinator    +46907851355      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Eisai Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03776136     History of Changes
Other Study ID Numbers: 7902-004
MK-7902-004 ( Other Identifier: Merck Protocol Number )
E7080-G000-225 ( Other Identifier: Eisai Protocol Number )
2018-002518-10 ( EudraCT Number )
LEAP-004 ( Other Grant/Funding Number: Merck )
First Posted: December 14, 2018    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
programmed cell death ligand 2 (PD-L2, PDL2)

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action