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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03820986




Registration number
NCT03820986
Ethics application status
Date submitted
22/01/2019
Date registered
29/01/2019

Titles & IDs
Public title
Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advance Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)
Scientific title
A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants With Advanced Melanoma (LEAP-003)
Secondary ID [1] 0 0
MK-7902-003
Secondary ID [2] 0 0
7902-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant 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: Other - Pembrolizumab
Treatment: Drugs - Lenvatinib
Treatment: Drugs - Placebo for lenvatinib

Experimental: Pembrolizumab+Lenvatinib - Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years.

Active comparator: Pembrolizumab+Placebo - Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.


Treatment: Other: Pembrolizumab
IV infusion

Treatment: Drugs: Lenvatinib
Oral capsule

Treatment: Drugs: Placebo for lenvatinib
Oral capsule
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 46 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 46 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1
Timepoint [1] 0 0
Up to approximately 46 months
Secondary outcome [2] 0 0
Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1
Timepoint [2] 0 0
Up to approximately 46 months
Secondary outcome [3] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [3] 0 0
Up to approximately 46 months
Secondary outcome [4] 0 0
Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)
Timepoint [4] 0 0
Up to approximately 46 months
Secondary outcome [5] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Global Health Status (GHS)/Quality of Life (QoL) Score
Timepoint [5] 0 0
Baseline and Week 21
Secondary outcome [6] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Physical Function (PF) Score
Timepoint [6] 0 0
Baseline and Week 21
Secondary outcome [7] 0 0
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS/QoL Score
Timepoint [7] 0 0
Up to approximately 30 months
Secondary outcome [8] 0 0
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 in Physical Function (PF) Score
Timepoint [8] 0 0
Up to approximately 30 months

Eligibility
Key inclusion criteria
* Has histologically or cytologically confirmed melanoma.
* Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy.
* Has been untreated for advanced or metastatic disease except as follows:

1. Proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. Participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after discussion with the medical monitor.
2. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [anti-PD-1] therapy or interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
* Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the Screening period (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).
* Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
* Has the presence of =1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.
* Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization.
* 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 contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period. Please note that 7 days after lenvatinib/placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed. Contraception 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.
* Female participants must not be pregnant, not breastfeeding, and =1 of the following conditions applies:

1. Not a woman of childbearing potential (WOCBP). OR
2. A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment.
* The participant (or legally acceptable representative) has provided documented informed consent for the study.
* Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
* 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 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. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
* Has known active central nervous system 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 (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, etc.) is not considered a form of systemic treatment.
* Has an active infection requiring systemic therapy.
* Has known history of human immunodeficiency virus (HIV) infection
* Has known history of or is positive for hepatitis B virus or hepatitis C virus infection.
* Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has a history of active tuberculosis (Bacillus tuberculosis).
* Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
* Has had a major surgery within 3 weeks prior to first dose of study intervention. Note: Adequate wound healing after major surgery must be assessed clinically independent of time elapsed for eligibility.
* Has a preexisting Grade =3 gastrointestinal or non-gastrointestinal fistula.
* Has radiographic evidence of encasement or invasion of major blood vessel, or of intratumoral cavitation.
* Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study treatment.
* Has clinically significant cardiovascular disease from 12 months of the first dose of study treatment 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 urine protein =1 g/24-hour. Note: Participants with =2+ (=100 mg/dL) proteinuria on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
* Prolongation of QTcF interval to >480 ms. Note: If the QTcF is prolonged to >480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.
* Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram.
* Has received prior therapy in the adjuvant setting. Note: Targeted therapy, anti-CTLA-4, or anti-PD-1 may be allowed.
* Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy as noted in Inclusion Criteria above
* Has received prior therapy with a monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study treatment or not recovered (=Grade 1 or at Baseline) from adverse events due to previously administered agents.

Exception to this rule would be use of denosumab, which is not excluded. Note: Participants with alopecia and =Grade 2 neuropathy are an exception and may enroll.

* Has received prior radiotherapy within 2 weeks of first dose of study treatment (Cycle 1 Day 1). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
* Has received 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 current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's 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
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 administering the treatment/s
The people assessing the outcomes
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
12/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/11/2024
Actual
Sample size
Target
Accrual to date
Final
674
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Lismore Base Hospital ( Site 0453) - Lismore
Recruitment hospital [2] 0 0
Melanoma Institute Australia ( Site 0452) - North Sydney
Recruitment hospital [3] 0 0
Westmead Hospital ( Site 0451) - Westmead
Recruitment hospital [4] 0 0
Princess Alexandra Hospital ( Site 0454) - Wooloongabba
Recruitment hospital [5] 0 0
Eastern Health ( Site 0457) - Box Hill
Recruitment hospital [6] 0 0
Fiona Stanley Hospital ( Site 0456) - Murdoch
Recruitment postcode(s) [1] 0 0
2480 - Lismore
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
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
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Florida
Country [5] 0 0
United States of America
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Illinois
Country [6] 0 0
United States of America
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Minnesota
Country [7] 0 0
United States of America
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Montana
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
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United States of America
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Oregon
Country [11] 0 0
United States of America
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Virginia
Country [12] 0 0
Austria
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Steiermark
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Austria
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Wien
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Brazil
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Minas Gerais
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Brazil
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Rio Grande Do Sul
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Brazil
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Rio de Janeiro
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Araucania
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Chile
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Region M. De Santiago
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Chile
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Valparaiso
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China
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Beijing
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China
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Fujian
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China
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Guangdong
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China
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Henan
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China
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Jiangsu
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China
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Jilin
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China
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Shanghai
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China
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Tianjin
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China
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Yunnan
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China
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Zhejiang
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France
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Alpes-Maritimes
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France
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Bouches-du-Rhone
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Cote-d Or
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France
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Haute-Garonne
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France
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Hauts-de-Seine
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France
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Nord
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France
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Seine-Maritime
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France
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Val-d Oise
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France
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Val-de-Marne
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France
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Vienne
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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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Sachsen
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Germany
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Schleswig-Holstein
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Germany
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Thuringen
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Israel
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Afula
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Israel
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Beer Sheva
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Israel
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Zerifin
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Italy
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Abruzzo
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Italy
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Toscana
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Italy
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Milano
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Italy
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Napoli
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Italy
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Padova
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Korea, Republic of
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Taegu-Kwangyokshi
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Korea, Republic of
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Seoul
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Poland
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Kujawsko-pomorskie
Country [65] 0 0
Poland
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Malopolskie
Country [66] 0 0
Poland
State/province [66] 0 0
Pomorskie
Country [67] 0 0
Poland
State/province [67] 0 0
Slaskie
Country [68] 0 0
Poland
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Wielkopolskie
Country [69] 0 0
South Africa
State/province [69] 0 0
Eastern Cape
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South Africa
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Gauteng
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South Africa
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Western Cape
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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La Coruna
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Spain
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Las Palmas
Country [76] 0 0
Spain
State/province [76] 0 0
Madrid
Country [77] 0 0
Spain
State/province [77] 0 0
Malaga
Country [78] 0 0
Sweden
State/province [78] 0 0
Jonkopings Lan
Country [79] 0 0
Sweden
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Kronobergs Lan
Country [80] 0 0
Sweden
State/province [80] 0 0
Skane Lan
Country [81] 0 0
Sweden
State/province [81] 0 0
Stockholms Lan
Country [82] 0 0
Sweden
State/province [82] 0 0
Uppsala Lan
Country [83] 0 0
Sweden
State/province [83] 0 0
Vasterbottens Lan
Country [84] 0 0
Sweden
State/province [84] 0 0
Vastra Gotalands Lan
Country [85] 0 0
Switzerland
State/province [85] 0 0
Basel-Stadt
Country [86] 0 0
Switzerland
State/province [86] 0 0
Grisons
Country [87] 0 0
Switzerland
State/province [87] 0 0
Zurich
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Edinburgh, City Of
Country [89] 0 0
United Kingdom
State/province [89] 0 0
London, City Of
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Plymouth
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Swansea

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 not provided in https://clinicaltrials.gov/study/NCT03820986