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Advanced MelanomaPhase 2NCT03776136

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)

A Phase 2 study testing lenvatinib and pembrolizumab in people with Advanced Melanoma, run by Merck Sharp & Dohme LLC at 23 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Melanoma
What is being tested?
lenvatinib and pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
103 participants
Where
23 sitesin 5 countries
Study dates
30 Jan 2019to 11 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

23 sites in 5 countries.

23 sites in 5 countries

United States6 sites

  • Ironwood Cancer & Research Centers ( Site 0312)

    Chandler, Arizona, 85224

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

    Dallas, Texas, 75246

  • Inova Schar Cancer Institute ( Site 0314)

    Fairfax, Virginia, 22031-4867

  • Southeast Nebraska Cancer Center ( Site 0316)

    Lincoln, Nebraska, 68510

  • Advocate Medical Group-Park Ridge ( Site 0313)

    Park Ridge, Illinois, 60068

  • John Wayne Cancer Institute ( Site 0301)

    Santa Monica, California, 90404

Other trials in United States

Australia5 sites

  • Box Hill Hospital ( Site 0157)

    Box Hill, Victoria, 3128

  • Lismore Base Hospital ( Site 0153)

    Lismore, 2480

  • Fiona Stanley Hospital ( Site 0156)

    Perth, Western Australia, 6150

  • Melanoma Institute Australia ( Site 0152)

    Wollstonecraft, New South Wales, 2065

  • Princess Alexandra Hospital ( Site 0154)

    Woolloongabba, Queensland, 4102

Other trials in Australia

Canada4 sites

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

    Montreal, Quebec, H2X 3E4

  • McGill University Health Centre ( Site 0651)

    Montreal, Quebec, H4A 3J1

  • Sunnybrook Research Institute ( Site 0654)

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre ( Site 0655)

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Spain4 sites

  • Hospital Clinic i Provincial Barcelona ( Site 0001)

    Barcelona, 08036

  • Hospital General Universitario Gregorio Maranon ( Site 0003)

    Madrid, 28007

  • Hospital Universitario Virgen de la Macarena ( Site 0004)

    Seville, 41009

  • Hospital General Universitario de Valencia ( Site 0002)

    Valencia, 46014

Other trials in Spain

Sweden4 sites

  • Sahlgrenska Universitetssjukhuset ( Site 0052)

    Gothenburg, 413 45

  • Skanes Universitetssjukhus ( Site 0053)

    Lund, 221 85

  • Karolinska Universitetssjukhuset ( Site 0051)

    Solna, 171 64

  • Norrlands Universitetssjukhus ( Site 0056)

    Umeå, 901 85

Other trials in Sweden

About this study

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)

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.

Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2)
Medical subject headings
Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • lenvatinibDrug

    Also called MK-7902, E7080, LENVIMA™

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

  • pembrolizumabBiological

    Also called MK-3475, Keytruda®

    Administered as an IV infusion on Day 1 Q3W.

Study groups in NCT03776136
Study groupRoleWhat they receive
lenvatinib plus pembrolizumabExperimentalParticipants 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.
Receives: Drug: lenvatinib; Biological: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants in the analysis population who have a confirmed Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ).

    Measured: Up to approximately 55 months

Secondary outcomes (6)

  1. Progression-free Survival (PFS)

    PFS was defined as the time from first day of study intervention to the first documented progressive disease (PD) per RECIST 1.1 by BICR, or death from any cause, whichever occurred first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). PFS was calculated using the nonparametric Kaplan-Meier method; participants who did not experience a PFS event were censored at the last disease assessment, or the last assessment before new anticancer treatment if new treatment was initiated.

    Measured: Up to approximately 55 months

  2. Overall Survival (OS)

    OS was defined as the time from the first day of study intervention to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was calculated using the nonparametric Kaplan-Meier method.

    Measured: Up to approximately 55 months

  3. Duration of Response (DOR)

    For participants who demonstrated a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per RECIST 1.1, DOR was defined as the time from first documented CR or PR until progressive disease (PD) or death from any cause, whichever occurs first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). DOR was calculated using the nonparametric Kaplan-Meier method for censored data.

    Measured: Up to approximately 55 months

  4. Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)

    AUC0-inf was defined as the area under the concentration-time curve from time zero extrapolated to infinity. Plasma blood samples collected at specified timepoints, were used to estimate AUC0-inf following Lenvatinib and Pembrolizumab administration. Based on the lenvatinib plasma concentration data obtained on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, a protocol specified population PK analysis was performed to characterize the steady state AUC0-inf of lenvatinib when co-administered with pembrolizumab.

    Measured: Cycle 1 Day 1: 0.5 to 4 hours and 6 to 10 hours postdose; Cycle 1 Day 15: Predose and 2 to 12 hours postdose; Cycle 2 Day 1: Predose, 0.5 to 4 hours, and 6 to 10 hours post-dose (each cycle =21 days)

  5. Number of Participants Who Experience At Least One Adverse Event (AE)

    An AE was 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. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented.

    Measured: Up to approximately 55 months

  6. Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE was 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. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented.

    Measured: Up to approximately 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2018
  2. Study start30 Jan 2019
  3. Primary completion11 Oct 2023
  4. Study completion11 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03776136
Sponsor's protocol ID
7902-004
Other IDs
MK-7902-004, E7080-G000-225, LEAP-004, 2018-002518-10, 2018
Status last verified
Sep 2024
First submitted
13 Dec 2018
Last updated
9 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 35867951

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lenvatinib and pembrolizumab in people with Advanced Melanoma, run by Merck Sharp & Dohme LLC at 23 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Australia, Canada, Spain, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Up to approximately 55 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03776136, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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