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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03776136




Registration number
NCT03776136
Ethics application status
Date submitted
13/12/2018
Date registered
14/12/2018
Date last updated
23/05/2019

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
MK-7902-004
Secondary ID [2] 0 0
7902-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lenvatinib
Other interventions - pembrolizumab

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.


Treatment: Drugs: lenvatinib
Administered orally once a day during each 21-day cycle.

Other interventions: pembrolizumab
Administered as an IV infusion on Day 1 Q3W.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) - 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.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) - 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.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from the first day of study treatment to death due to any cause.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Duration of Response (DOR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) - 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.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Percentage of Participants Who Experience At Least One Adverse Event (AE) - 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.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - 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.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf) - 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.
Timepoint [6] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia ( Site 0152) - Wollstonecraft
Recruitment hospital [2] 0 0
Princess Alexandra Hospital ( Site 0154) - Woolloongabba
Recruitment hospital [3] 0 0
Box Hill Hospital ( Site 0157) - Box Hill
Recruitment hospital [4] 0 0
Fiona Stanley Hospital ( Site 0156) - Perth
Recruitment hospital [5] 0 0
Lismore Base Hospital ( Site 0153) - Lismore
Recruitment postcode(s) [1] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
6150 - Perth
Recruitment postcode(s) [5] 0 0
2480 - Lismore
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Nebraska
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Spain
State/province [9] 0 0
Barcelona
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Spain
State/province [11] 0 0
Sevilla
Country [12] 0 0
Spain
State/province [12] 0 0
Valencia
Country [13] 0 0
Sweden
State/province [13] 0 0
Goteborg
Country [14] 0 0
Sweden
State/province [14] 0 0
Lund
Country [15] 0 0
Sweden
State/province [15] 0 0
Solna
Country [16] 0 0
Sweden
State/province [16] 0 0
Umea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03776136
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03776136