Clinical trial NCT03820986: 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)
Official 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malignant Melanoma
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death-ligand 1 (PD-L1, PDL1)
programmed cell death-ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2019-01-29
Enrollment: 674
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma.

The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Detailed description: As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 46 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 46 months
Secondary outcomes:
measure: Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1
timeFrame: Up to approximately 46 months
measure: Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1
timeFrame: Up to approximately 46 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 46 months
measure: Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)
timeFrame: Up to approximately 46 months
measure: 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
timeFrame: Baseline and Week 21
measure: 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
timeFrame: Baseline and Week 21
measure: Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS/QoL Score
timeFrame: Up to approximately 30 months
measure: Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 in Physical Function (PF) Score
timeFrame: Up to approximately 30 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute ( Site 0707)
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704)
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute ( Site 0705)
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute ( Site 0706)
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center ( Site 0708)
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center ( Site 0709)
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center ( Site 0767)
state: Florida
city: Orange City
country: United States
facility: Mid-Florida Cancer Centers ( Site 0764)
state: Florida
city: Park Ridge
country: United States
facility: AMG Oncology ( Site 0714)
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care, PC ( Site 0765)
state: Illinois
city: Fridley
country: United States
facility: Minnesota Oncology Specialist, PA ( Site 0766)
state: Minnesota
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center ( Site 0724)
state: Montana
city: Morristown
country: United States
facility: Atlantic Health System ( Site 0768)
state: New Jersey
city: Paramus
country: United States
facility: Valley Hospital ( Site 0749)
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina - Cancer Hospital ( Site 0751)
state: North Carolina
city: Portland
country: United States
facility: OHSU Center for Health & Healing ( Site 0731)
state: Oregon
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute ( Site 0739)
state: Virginia
city: Lismore
country: Australia
facility: Lismore Base Hospital ( Site 0453)
state: Australian Capital Territory
city: North Sydney
country: Australia
facility: Melanoma Institute Australia ( Site 0452)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 0451)
state: New South Wales
city: Wooloongabba
country: Australia
facility: Princess Alexandra Hospital ( Site 0454)
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health ( Site 0457)
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 0456)
state: Western Australia
city: Graz
country: Austria
facility: LKH Universitatsklinikum Graz ( Site 0776)
state: Steiermark
city: Wien
country: Austria
facility: Medizinische Universitat Wien ( Site 0778)
city: Belo Horizonte
country: Brazil
facility: PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399)
state: Minas Gerais
city: Ijui
country: Brazil
facility: Hospital de Caridade de Ijui ( Site 0391)
state: Rio Grande Do Sul
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo ( Site 0396)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397)
state: Rio Grande Do Sul
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394)
city: Kelowna
country: Canada
facility: BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661)
state: British Columbia
city: North Vancouver
country: Canada
facility: Lions Gate Hospital ( Site 0662)
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Research Institute ( Site 0654)
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre ( Site 0651)
state: Quebec
city: Temuco
country: Chile
facility: Centro Investigación del Cáncer James Lind ( Site 0425)
state: Araucania
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez FALP ( Site 0421)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile ( Site 0422)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Sociedad Medica Aren y Bachero Limitada ( Site 0426)
state: Region M. De Santiago
city: Vina del Mar
country: Chile
facility: Oncocentro ( Site 0424)
state: Valparaiso
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0601)
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 0612)
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center ( Site 0602)
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital ( Site 0610)
state: Henan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital ( Site 0609)
state: Jiangsu
city: Chang Chun
country: China
facility: The First Hospital Of Jilin University ( Site 0603)
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 0607)
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital ( Site 0606)
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital ( Site 0604)
state: Yunnan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital ( Site 0605)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 0608)
state: Zhejiang
city: Nice
country: France
facility: Hopital ARCHET 2 ( Site 0009)
state: Alpes-Maritimes
city: Marseille
country: France
facility: Hopital La Timone ( Site 0002)
state: Bouches-du-Rhone
city: Dijon
country: France
facility: CHU Dijon Bourgogne ( Site 0010)
state: Cote-d Or
city: Toulouse
country: France
facility: Institut Claudius Regaud IUCT Oncopole ( Site 0003)
state: Haute-Garonne
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Pare Boulogne ( Site 0007)
state: Hauts-de-Seine
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez ( Site 0004)
state: Nord
city: Rouen
country: France
facility: CHU de Rouen ( Site 0013)
state: Seine-Maritime
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy ( Site 0012)
state: Val-d Oise
city: Villejuif
country: France
facility: Institut Gustave Roussy ( Site 0001)
state: Val-de-Marne
city: Poitiers
country: France
facility: CHU de la Miletrie Poitiers ( Site 0011)
state: Vienne
city: Hannover
country: Germany
facility: Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035)
state: Baden-Wurttemberg
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen ( Site 0044)
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036)
state: Bayern
city: Buxtehude
country: Germany
facility: Hautkrebszentrum Buxtehude ( Site 0037)
state: Niedersachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus ( Site 0041)
state: Sachsen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig ( Site 0040)
state: Sachsen
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033)
state: Schleswig-Holstein
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH ( Site 0042)
state: Thuringen
city: Afula
country: Israel
facility: HaEmek Medical Center ( Site 0306)
city: Beer Sheva
country: Israel
facility: Soroka Medical Center ( Site 0303)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0301)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hebrew University Medical Center ( Site 0305)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0302)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0304)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0307)
city: Zerifin
country: Israel
facility: Shamir Medical Center-Assaf Harofeh ( Site 0308)
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII ( Site 0062)
state: Abruzzo
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese ( Site 0065)
state: Toscana
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia ( Site 0067)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale ( Site 0061)
city: Padova
country: Italy
facility: Istituto Oncologico Veneto ( Site 0063)
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital ( Site 0553)
state: Taegu-Kwangyokshi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0554)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0552)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0551)
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273)
state: Kujawsko-pomorskie
city: Krakow
country: Poland
facility: Pratia MCM Krakow ( Site 0280)
state: Malopolskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne ( Site 0281)
state: Pomorskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278)
state: Slaskie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272)
state: Wielkopolskie
city: Port Elizabeth
country: South Africa
facility: Cancer Care Langenhoven Drive Oncology Centre ( Site 0805)
state: Eastern Cape
city: Johannesburg
country: South Africa
facility: Sandton Oncology Medical Group PTY LTD ( Site 0802)
state: Gauteng
city: Kraaifontein
country: South Africa
facility: Cape Town Oncology Trials Pty Ltd ( Site 0803)
state: Western Cape
city: Hospitalet del Llobregat
country: Spain
facility: Hospital Duran i Reinals ICO de Hospitalet ( Site 0187)
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla ( Site 0181)
state: Cantabria
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182)
state: La Coruna
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria ( Site 0189)
state: Las Palmas
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial Barcelona ( Site 0190)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 0191)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal ( Site 0183)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0184)
city: Malaga
country: Spain
facility: Hospital Universitario Carlos Haya ( Site 0186)
city: Jonkoping
country: Sweden
facility: Laenssjukhuset Ryhov ( Site 0215)
state: Jonkopings Lan
city: Vaxjo
country: Sweden
facility: Centrallasarettet Vaxjo ( Site 0214)
state: Kronobergs Lan
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus ( Site 0213)
state: Skane Lan
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset ( Site 0211)
state: Stockholms Lan
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset ( Site 0218)
state: Uppsala Lan
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus ( Site 0216)
state: Vasterbottens Lan
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset ( Site 0212)
state: Vastra Gotalands Lan
city: Basel
country: Switzerland
facility: Universitaetsspital Basel ( Site 0094)
state: Basel-Stadt
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden ( Site 0091)
state: Grisons
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur ( Site 0095)
state: Zurich
city: Zuerich-Flughafen
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 0092)
state: Zurich
city: Edinburgh
country: United Kingdom
facility: Western General Hospital ( Site 0121)
state: Edinburgh, City Of
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust ( Site 0126)
state: London, City Of
city: Plymouth
country: United Kingdom
facility: Derriford Hospital ( Site 0129)
city: Swansea
country: United Kingdom
facility: Singleton Hospital ( Site 0131)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: