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)

NCT ID: NCT03776136

Last Updated: 2024-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-30
• Study Completion Date: 2023-10-11

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-programmed cell death ligand 1 (PD-1/L1) agents approved for unresectable or metastatic melanoma. No statistical hypothesis will be tested in this study.

Conditions

Advanced Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

lenvatinib

Intervention Type: DRUG

Administered orally once a day during each 21-day cycle.

pembrolizumab

Intervention Type: BIOLOGICAL

Administered as an IV infusion on Day 1 Q3W.

Interventions

lenvatinib

Administered orally once a day during each 21-day cycle.

Intervention Type: DRUG

pembrolizumab

Administered as an IV infusion on Day 1 Q3W.

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-7902; E7080; LENVIMA™; MK-3475; Keytruda®

Eligibility 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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Ironwood Cancer & Research Centers ( Site 0312)

Chandler, Arizona, United States

John Wayne Cancer Institute ( Site 0301)

Santa Monica, California, United States

Advocate Medical Group-Park Ridge ( Site 0313)

Park Ridge, Illinois, United States

Southeast Nebraska Cancer Center ( Site 0316)

Lincoln, Nebraska, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0317)

Dallas, Texas, United States

Inova Schar Cancer Institute ( Site 0314)

Fairfax, Virginia, United States

Melanoma Institute Australia ( Site 0152)

Wollstonecraft, New South Wales, Australia

Princess Alexandra Hospital ( Site 0154)

Woolloongabba, Queensland, Australia

Box Hill Hospital ( Site 0157)

Box Hill, Victoria, Australia

Fiona Stanley Hospital ( Site 0156)

Perth, Western Australia, Australia

Lismore Base Hospital ( Site 0153)

Lismore, , Australia

Sunnybrook Research Institute ( Site 0654)

Toronto, Ontario, Canada

Princess Margaret Cancer Centre ( Site 0655)

Toronto, Ontario, Canada

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)

Montreal, Quebec, Canada

McGill University Health Centre ( Site 0651)

Montreal, Quebec, Canada

Hospital Clinic i Provincial Barcelona ( Site 0001)

Barcelona, , Spain

Hospital General Universitario Gregorio Maranon ( Site 0003)

Madrid, , Spain

Hospital Universitario Virgen de la Macarena ( Site 0004)

Seville, , Spain

Hospital General Universitario de Valencia ( Site 0002)

Valencia, , Spain

Sahlgrenska Universitetssjukhuset ( Site 0052)

Gothenburg, , Sweden

Skanes Universitetssjukhus ( Site 0053)

Lund, , Sweden

Karolinska Universitetssjukhuset ( Site 0051)

Solna, , Sweden

Norrlands Universitetssjukhus ( Site 0056)

Umeå, , Sweden

Countries

United States; Australia; Canada; Spain; Sweden

References

Arance A, de la Cruz-Merino L, Petrella TM, Jamal R, Ny L, Carneiro A, Berrocal A, Marquez-Rodas I, Spreafico A, Atkinson V, Costa Svedman F, Mant A, Khattak MA, Mihalcioiu C, Jang S, Cowey CL, Smith AD, Hawk N, Chen K, Diede SJ, Krepler C, Long GV. Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. J Clin Oncol. 2023 Jan 1;41(1):75-85. doi: 10.1200/JCO.22.00221. Epub 2022 Jul 22.

Reference Type: DERIVED

PMID: 35867951 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

MK-7902-004

Identifier Type: OTHER

Identifier Source: secondary_id

E7080-G000-225

Identifier Type: OTHER

Identifier Source: secondary_id

LEAP-004

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2018-002518-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7902-004

Identifier Type: -

Identifier Source: org_study_id