Clinical trial NCT06357533: Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations
Official title: A Phase III, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations (TROPION-Lung10)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: NSCLC
Non-Small Cell Lung Cancer
Datopotamab Deruxtecan
Rilvegostomig
Pembrolizumab
Non-squamous
PD-L1 expression >=50%
Locally-advanced NSCLC
Metastatic NSCLC
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2024-04-10
Enrollment: 675
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Detailed description: This is a Phase III, randomized, open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig monotherapy versus Pembrolizumab monotherapy for the first-line treatment of participants with locally-advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically documented non-squamous NSCLC.
* Stage IIIB or IIIC or Stage IV metastatic NSCLC (according to Edition 8 of the AJCC staging manual) not amenable to curative surgery or definitive chemoradiation.
* Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for any other known genomic alteration for which there are locally approved and available targeted first-line therapies.
* Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers.
* Known tumour PD-L1 expression status defined as TC ≥ 50%
* At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline
* ECOG performance status of 0 or 1
* Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention

Exclusion Criteria:

* Prior systemic therapy for advanced/metastatic NSCLC.
* Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
* History of another primary malignancy within 3 years
* Active or prior documented autoimmune or inflammatory disorders (with exceptions)
* Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
* Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
* History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
* Has significant pulmonary function compromise, as determined by the investigator
* Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
* History of leptomeningeal carcinomatosis
* Known clinically significant corneal disease
* Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled
* History of active primary immunodeficiency

Primary outcomes:
measure: Progression-Free Survival (PFS) in TROP2 biomarker positive participants.
timeFrame: Approximately 4 years
measure: Overall Survival (OS) in TROP2 biomarker positive participants.
timeFrame: Approximately 6 years
Secondary outcomes:
measure: Progression-Free Survival (PFS) in the FAS population.
timeFrame: Approximately 4 years
measure: Overall Survival (OS) in the FAS population.
timeFrame: Approximately 6 years
measure: Assessment of Objective Response Rate (ORR) by BICR in TROP2 biomarker positive and FAS populations
timeFrame: Approximately 4 years
measure: Assessment of Duration of Response (DoR) by BICR in TROP2 biomarker positive and FAS populations
timeFrame: Approximately 4 years
measure: Participant-reported lung cancer symptoms of NSCLC and participant-reported GHS/QOL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab.
timeFrame: Approximately 6 years
measure: Participant-reported physical functioning in participants treated with Dato DXd in combination with rilvegostomig relative to pembrolizumab.
timeFrame: Approximately 6 years
measure: Pharmacokinetics (PK)
timeFrame: Approximately 6 years
measure: Immunogenicity
timeFrame: Approximately 6 years
measure: Second Progression-Free Survival (PFS2).
timeFrame: Approximately 6 years
Other outcomes:
measure: Safety of Dato-DXd in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab.
timeFrame: Approximately 6 years
Locations:
city: Anchorage
country: United States
facility: Research Site
state: Alaska
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Springdale
country: United States
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state: Arkansas
city: Anaheim
country: United States
facility: Research Site
state: California
city: Beverly Hills
country: United States
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state: California
city: Fountain Valley
country: United States
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state: California
city: Newport Beach
country: United States
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state: California
city: Gainesville
country: United States
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state: Florida
city: Miami Beach
country: United States
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state: Florida
city: Orange City
country: United States
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state: Florida
city: Orlando
country: United States
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state: Florida
city: Punta Gorda
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Atlanta
country: United States
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state: Georgia
city: Atlanta
country: United States
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state: Georgia
city: Atlanta
country: United States
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state: Georgia
city: Noblesville
country: United States
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state: Indiana
city: Annapolis
country: United States
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state: Maryland
city: Boston
country: United States
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state: Massachusetts
city: Boston
country: United States
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state: Massachusetts
city: Dearborn
country: United States
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state: Michigan
city: Farmington Hills
country: United States
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state: Michigan
city: Grand Rapids
country: United States
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state: Michigan
city: Traverse City
country: United States
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state: Michigan
city: Hattiesburg
country: United States
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state: Mississippi
city: Bozeman
country: United States
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state: Montana
city: Grand Island
country: United States
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state: Nebraska
city: Omaha
country: United States
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state: Nebraska
city: Las Vegas
country: United States
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state: Nevada
city: Reno
country: United States
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city: Voorhees
country: United States
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state: New Jersey
city: Stony Brook
country: United States
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state: New York
city: Greenville
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state: North Carolina
city: Salisbury
country: United States
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state: North Carolina
city: Cincinnati
country: United States
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city: Columbus
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city: Greenville
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city: Sioux Falls
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city: Chattanooga
country: United States
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city: Knoxville
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city: Fort Worth
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city: Houston
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city: Houston
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city: Houston
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city: Kingwood
country: United States
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city: Odessa
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city: Fort Belvoir
country: United States
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state: Virginia
city: Leesburg
country: United States
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state: Virginia
city: Richmond
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country: United States
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state: Washington
city: Vancouver
country: United States
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city: Wenatchee
country: United States
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state: Washington
city: Birtinya
country: Australia
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city: Blacktown
country: Australia
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city: Clayton
country: Australia
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city: Gosford
country: Australia
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city: Melbourne
country: Australia
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city: South Brisbane
country: Australia
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city: Southport
country: Australia
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city: Wodonga
country: Australia
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city: Innsbruck
country: Austria
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city: Krems
country: Austria
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city: Linz
country: Austria
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city: Rankweil
country: Austria
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city: Wels
country: Austria
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city: Wien
country: Austria
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city: Wien
country: Austria
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city: Anderlecht
country: Belgium
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city: Hasselt
country: Belgium
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city: La Louvière
country: Belgium
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city: Liège
country: Belgium
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city: Barretos
country: Brazil
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city: Curitiba
country: Brazil
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city: Florianópolis
country: Brazil
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city: Ipatinga
country: Brazil
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city: Natal
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Rio de Janeiro
country: Brazil
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city: Santa Maria
country: Brazil
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city: São Paulo
country: Brazil
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city: Taubaté
country: Brazil
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city: Vancouver
country: Canada
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state: British Columbia
city: Winnipeg
country: Canada
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state: Manitoba
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: London
country: Canada
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state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Oshawa
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Lévis
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Montreal
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state: Quebec
city: Rimouski
country: Canada
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state: Quebec
city: Trois-Rivieres
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state: Quebec
city: Saskatoon
country: Canada
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state: Saskatchewan
city: Chicoutimi
country: Canada
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city: Beijing
country: China
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city: Beijing
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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city: Jinan
country: China
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country: China
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city: Kunming
country: China
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city: Lanzhou
country: China
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city: Linhai
country: China
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city: Linyi
country: China
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city: Nanjing
country: China
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city: Nanning
country: China
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city: Nanning
country: China
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city: Shanghai
country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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country: China
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city: Zhengzhou City
country: China
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city: Zhengzhou
country: China
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city: Bonn
country: Germany
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city: Düsseldorf
country: Germany
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city: Essen
country: Germany
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city: Freiburg
country: Germany
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city: Gauting
country: Germany
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city: Georgsmarienhütte
country: Germany
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city: Gera
country: Germany
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city: Gütersloh
country: Germany
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city: Hamburg
country: Germany
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city: Hamburg
country: Germany
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city: Heidelberg
country: Germany
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city: Kempten
country: Germany
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city: Koblenz
country: Germany
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city: Ludwigsburg
country: Germany
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city: München
country: Germany
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city: Nürnberg
country: Germany
facility: Research Site
city: Ravensburg
country: Germany
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city: Budapest
country: Hungary
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city: Gyula
country: Hungary
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city: Gyöngyös
country: Hungary
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city: Győr
country: Hungary
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city: Kecskemét
country: Hungary
facility: Research Site
city: Salgótarján
country: Hungary
facility: Research Site
city: Szekszárd
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
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city: Törökbálint
country: Hungary
facility: Research Site
city: Chennai
country: India
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city: Dwarka
country: India
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city: Jaipur
country: India
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city: Kolkata
country: India
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city: Marg Jaipur
country: India
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city: Nagpur
country: India
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city: Nashik
country: India
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city: New Delhi
country: India
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city: New Delhi
country: India
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city: Thiruvananthapuram
country: India
facility: Research Site
city: Bergamo
country: Italy
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city: Genoa
country: Italy
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city: Milano
country: Italy
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city: Milano
country: Italy
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city: Monza
country: Italy
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city: Padova
country: Italy
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city: Pavia
country: Italy
facility: Research Site
city: Ravenna
country: Italy
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city: Roma
country: Italy
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city: Rozzano
country: Italy
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city: Fukuoka-shi
country: Japan
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city: Fukuoka-shi
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
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city: Hirosaki-shi
country: Japan
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city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kawasaki-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Okayama
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Sagamihara-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Takaoka-shi
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Tokushima-shi
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Utsunomiya-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Changwon
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Przemysl
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: San Juan
country: Puerto Rico
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Jerez de la Frontera
country: Spain
facility: Research Site
city: Reus,Tarragona
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Mueang
country: Thailand
facility: Research Site
city: Mueang
country: Thailand
facility: Research Site
city: Adapazarı
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Cheltenham
country: United Kingdom
facility: Research Site
city: Inverness
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Preston
country: United Kingdom
facility: Research Site
city: Truro
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Emory University, Atlanta, Georgia, United States of America.
name: Suresh S. Ramalingam, MD
role: PRINCIPAL_INVESTIGATOR
References: