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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04199104




Registration number
NCT04199104
Ethics application status
Date submitted
12/12/2019
Date registered
13/12/2019
Date last updated
23/04/2021

Titles & IDs
Public title
A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010)
Scientific title
A Phase 3, Randomized, Placebo-controlled, Double-blind Clinical Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) to Evaluate the Safety and Efficacy of Pembrolizumab and Lenvatinib as 1L Intervention in a PD-L1 Selected Population of Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010).
Secondary ID [1] 0 0
MK-7902-010
Secondary ID [2] 0 0
7902-010
Universal Trial Number (UTN)
Trial acronym
LEAP-10
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Placebo

Experimental: Pembrolizumab with Lenvatinib - 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.

Active Comparator: Pembrolizumab with Placebo - Participants receive lenvatinib-matching placebo 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).


Treatment: Drugs: Lenvatinib
Lenvatinib, 20 mg (two 10-mg oral capsules) administered QD

Treatment: Drugs: Pembrolizumab
Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles

Treatment: Drugs: Placebo
Lenvatinib-matching placebo, oral capsules, administered once daily (QD)

Intervention code [1] 0 0
Treatment: Drugs
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) as Assessed by Blinded Independent Central Review (BICR). - ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.
Timepoint [1] 0 0
Up to approximately 24 months
Primary outcome [2] 0 0
Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR). - PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD.
Timepoint [2] 0 0
Up to approximately 30 months
Primary outcome [3] 0 0
Overall Survival (OS) - OS is the time from randomization to death due to any cause.
Timepoint [3] 0 0
Up to approximately 44 months
Secondary outcome [1] 0 0
Duration of Response (DOR) - For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.
Timepoint [1] 0 0
Up to approximately 44 months
Secondary outcome [2] 0 0
Number of Participants Who Experienced an Adverse Event (AE) - An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Timepoint [2] 0 0
Up to approximately 44 months
Secondary outcome [3] 0 0
Number of Participants Who Discontinued Study Drug Due to an AE - An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Timepoint [3] 0 0
Up to approximately 44 months

Eligibility
Key inclusion criteria
- Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by
local therapies.

Note: Participants with newly-diagnosed HNSCC must be M1/Stage IV.

- Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.

Note: Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not
eligible.

- Male participants agree to use approved contraception during the treatment period for
at least 30 days after the last dose of lenvatinib/placebo, or refrain from
heterosexual intercourse during this period

- Female participants are not pregnant or breastfeeding, and are not a woman of
childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during
the treatment period (or 14 days prior to the initiation of study treatment for oral
contraception) and for at least 120 days post pembrolizumab, or 30 days post
lenvatinib/placebo, whichever occurs last

- Has measurable disease per RECIST 1.1 as assessed by BICR. Note: Lesions situated in a
previously irradiated area are considered measurable if progression has been
demonstrated in such lesions.

- Participants with oropharyngeal cancer must have results from testing of human
papillomavirus HPV status.

- Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.

- Has adequately controlled blood pressure with or without antihypertensive medications.

- 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 history of any contraindication or has a severe hypersensitivity to any
components of pembrolizumab (=Grade 3) or lenvatinib.

- Has pre-existing =Grade 3 gastrointestinal or non-gastrointestinal fistula.

- Has a history of a gastrointestinal condition or procedure that, in the opinion of the
investigator, may affect oral study drug absorption.

- Has clinically significant cardiovascular impairment within 12 months of the first
dose of study drug, such as history of congestive heart failure greater than New York
Heart Association (NYHA) Class II, unstable angina, myocardial infarction or
cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac
revascularization, or cardiac arrhythmia associated with hemodynamic instability.

- Has disease that is suitable for local therapy administered with curative intent.

- Had PD within 6 months of completion of curatively intended systemic treatment for
locoregionally advanced HNSCC.

- Has had major surgery within 3 weeks prior to first dose of study interventions.

- Has difficulty swallowing capsules or ingesting a suspension either orally or by a
nasogastric (NG) tube.

- Has received prior therapy with lenvatinib or pembrolizumab.

- Received last dose of systemic therapy for locoregionally advanced disease less than 6
months prior to signing consent.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX-40, CD137).

- Has received prior systemic anticancer therapy including investigational agents within
4 weeks prior to randomization.

- Has received prior radiotherapy within 2 weeks of start of study intervention.

- Has received a live vaccine within 30 days prior to the first dose of study drug.

- 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 intervention.

- 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 prior the first dose of study drug.

- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.

- Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed.

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.

- Has an active infection requiring systemic therapy.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has a known history of hepatitis B (defined as HBsAg reactive) or known active
hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected)
infection.

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis).

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study intervention.

- Has had an allogenic tissue/solid organ transplant.

- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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,SA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 1002) - Camperdown
Recruitment hospital [2] 0 0
St George Hospital ( Site 1001) - Kogarah
Recruitment hospital [3] 0 0
Royal Adelaide Hospital ( Site 1004) - Adelaide
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
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Kansas
Country [6] 0 0
United States of America
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Kentucky
Country [7] 0 0
United States of America
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Massachusetts
Country [8] 0 0
United States of America
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Michigan
Country [9] 0 0
United States of America
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Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Montana
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Brazil
State/province [19] 0 0
Ceara
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Brazil
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Minas Gerais
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Brazil
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Parana
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Canada
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Ontario
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Quebec
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China
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Beijing
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China
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Chongqing
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Fujian
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Guangxi
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China
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Heilongjiang
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China
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Henan
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China
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Hubei
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China
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Hunan
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China
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Jiangxi
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China
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Jilin
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China
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Shaanxi
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China
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Shanghai
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China
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Sichuan
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China
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Tianjin
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China
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Zhejiang
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France
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Auvergne
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France
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Bouches-du-Rhone
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Hauts-de-Seine
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Seine-Maritime
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Val-de-Marne
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Germany
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Hungary
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Borsod-Abauj-Zemplen
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Hungary
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Csongrad
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Hungary
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Jasz-Nagykun-Szolnok
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Hungary
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Budapest
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Hungary
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Debrecen
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Italy
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Brescia
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Italy
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Milano
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Italy
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Padova
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Italy
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Savona
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Japan
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Aichi
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Chiba
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Kagawa
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Kanagawa
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Osaka
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Shizuoka
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Japan
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Fukuoka
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Hiroshima
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Tokyo
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Korea, Republic of
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Jeonranamdo
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul
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Korea, Republic of
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Taegu-Kwangyokshi
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Mexico
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Nuevo Leon
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Mexico
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Quintana Roo
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Mexico
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Oaxaca
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Peru
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Lima
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Poland
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Dolnoslaskie
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Poland
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Kujawsko-pomorskie
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Malopolskie
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Poland
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Pomorskie
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Poland
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Slaskie
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Poland
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Wielkopolskie
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Russian Federation
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Altayskiy Kray
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Russian Federation
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Moskva
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Russian Federation
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Tatarstan, Respublika
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Yaroslavskaya Oblast
Country [86] 0 0
Spain
State/province [86] 0 0
Barcelona
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Spain
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Madrid
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Spain
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Sevilla
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Spain
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Zaragoza
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Taiwan
State/province [90] 0 0
Tainan
Country [91] 0 0
Taiwan
State/province [91] 0 0
Kaohsiung
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Taiwan
State/province [92] 0 0
Taipei
Country [93] 0 0
Turkey
State/province [93] 0 0
Ankara
Country [94] 0 0
Turkey
State/province [94] 0 0
Edirne
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Malatya
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Aberdeen City
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United Kingdom
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London, City Of
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United Kingdom
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Nottinghamshire
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United Kingdom
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Somerset
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Manchester

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 is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a
first line intervention in a PD-L1 selected population with participants with recurrent or
metastatic head and neck squamous cell carcinoma.

Hypotheses include:

- Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version
1.1 (RECIST 1.1) by blinded independent central review (BICR).

- Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to
Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR.

- Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to
overall survival (OS).
Trial website
https://clinicaltrials.gov/show/NCT04199104
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director, MD
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/NCT04199104