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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04199104
Ethics application status
Date submitted
12/12/2019
Date registered
13/12/2019

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) (MK-7902-010) (KEYNOTE-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
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: Other - 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: Other: 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
Intervention code [2] 0 0
Treatment: Other
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)
Timepoint [1] 0 0
Up to ~ 37 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).
Timepoint [2] 0 0
Up to ~ 37 months
Primary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Up to ~ 37 months
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Up to ~ 37 months
Secondary outcome [2] 0 0
Percentage of Participants Who Experienced an Adverse Event (AE)
Timepoint [2] 0 0
Up to ~ 37 months
Secondary outcome [3] 0 0
Percentage of Participants Who Discontinued Study Drug Due to an AE
Timepoint [3] 0 0
Up to ~ 34 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 (including p16+ unknown primary) are not eligible.

Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

* Male participants agree to use approved contraception during the treatment period for at least 7 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 shown 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.
* Have adequately controlled blood pressure with or without antihypertensive medications.
* Has adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
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 intervention, 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 before to first dose of study interventions.
* Has difficulty swallowing capsules or ingesting a suspension orally or by a feeding tube.
* Has received prior therapy with lenvatinib or pembrolizumab.
* Received last dose of systemic therapy for locoregionally advanced disease less than 6 months before 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 before randomization.
* Has received prior radiotherapy within 2 weeks of start of study intervention.
* Has received a live vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
* Received an investigational agent or has used an investigational device within 4 weeks prior to study intervention-administration.
* 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 intervention.
* 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. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) is allowed.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy. (e.g., tuberculosis, known viral or bacterial infections, etc.).
* 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.
* 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/12/2024
Actual
Sample size
Target
Accrual to date
Final
511
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
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United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Kansas
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United States of America
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Kentucky
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United States of America
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Massachusetts
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United States of America
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Michigan
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Missouri
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Montana
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Nebraska
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New Jersey
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New York
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North Carolina
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Oregon
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Virginia
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Washington
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United States of America
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Wisconsin
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Brazil
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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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Canada
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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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China
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Fujian
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China
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Guangxi
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China
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Guizhou
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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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France
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Hauts-de-Seine
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France
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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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Hessen
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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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Germany
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Sachsen
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Germany
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Berlin
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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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Vas
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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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Japan
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Chiba
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Japan
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Hyogo
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Japan
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Kagawa
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Japan
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Kanagawa
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Fukuoka
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Japan
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Hiroshima
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Japan
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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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Distrito Federal
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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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Muni Metro De Lima
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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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Poland
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Malopolskie
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Poland
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Mazowieckie
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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
State/province [91] 0 0
Wielkopolskie
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Altayskiy Kray
Country [93] 0 0
Russian Federation
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Moskva
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Russian Federation
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Tatarstan, Respublika
Country [95] 0 0
Russian Federation
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Yaroslavskaya Oblast
Country [96] 0 0
Spain
State/province [96] 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
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Tainan
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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Turkey
State/province [103] 0 0
Ankara
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Turkey
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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 [108] 0 0
United Kingdom
State/province [108] 0 0
Aberdeen City
Country [109] 0 0
United Kingdom
State/province [109] 0 0
London, City Of
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Nottinghamshire
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Somerset
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04199104