Clinical trial NCT05687266: Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations
Official title: A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: NSCLC
Keywords: Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Datopotamab deruxtecan (Dato-DXd)
Durvalumab
Carboplatin
Chemotherapy
Antibody-Drug Conjugate (ADC)
Trophoblast cell surface protein 2 (TROP2)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-01-18
Enrollment: 1350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).

Detailed description: Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment.

The primary objectives of the study are to demonstrate superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:

1. PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
2. OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
3. PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
4. OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC

Eligibility criteria: Inclusion:

* Participants ≥ 18 years at screening
* Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
* Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).

Testing is not required for tumors with squamous histology, with exceptions.

* ECOG PS of 0 or 1
* Archival tumour tissue
* Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion:

* Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
* History of another primary malignancy with exceptions
* Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
* Spinal cord compression or clinically or radiologically active brain metastases
* History of leptomeningeal carcinomatosis.
* Known active or uncontrolled hepatitis B or C virus infection.
* Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
* Clinically significant corneal disease
* 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.

Primary outcomes:
measure: Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population
timeFrame: Approximately 3 years
measure: Overall Survival (OS) in the non-squamous TROP2 biomarker positive population
timeFrame: Approximately 4 years
measure: PFS by BICR in the non-squamous population
timeFrame: Approximately 3 years
measure: OS in the non-squamous population
timeFrame: Approximately 4 years
Secondary outcomes:
measure: PFS by BICR in ITT and TROP2 biomarker-defined populations
timeFrame: Approximately 3 years
measure: OS in ITT and TROP2 biomarker-defined populations
timeFrame: Approximately 4 years
measure: Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations
timeFrame: Approximately 4 years
measure: Duration of Response (DoR) in ITT, non-squamous and TROP2 biomarker-defined populations
timeFrame: Approximately 4 years
measure: PFS by investigator in ITT, non-squamous and TROP2 biomarker-defined populations
timeFrame: Approximately 3 years
measure: Pharmacokinetics of Dato-DXd when combined with durvalumab and carboplatin.
timeFrame: Approximately 4 years
measure: Anti-Drug Antibody (ADA) for Dato-DXd
timeFrame: Approximately 4 years
measure: Time to Second Progression or Death (PFS2) in ITT, non-squamous and TROP2 biomarker-defined populations
timeFrame: Approximately 4 years
measure: Clinical Outcome Assessments in ITT, non-squamous and TROP2 biomarker-defined populations
timeFrame: Approximately 4 years
Other outcomes:
measure: Safety of Dato-DXd in combination with durvalumab and carboplatin
timeFrame: Approximately 4 years
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Hot Springs National Park
country: United States
facility: Research Site
state: Arkansas
city: Little Rock
country: United States
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state: Arkansas
city: Springdale
country: United States
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state: Arkansas
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Boulder
country: United States
facility: Research Site
state: Colorado
city: Fort Myers
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Lakeland
country: United States
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state: Florida
city: Saint Petersburg
country: United States
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state: Florida
city: West Palm Beach
country: United States
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state: Florida
city: Hinsdale
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state: Illinois
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Bettendorf
country: United States
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state: Iowa
city: Des Moines
country: United States
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state: Iowa
city: Iowa City
country: United States
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state: Iowa
city: Baton Rouge
country: United States
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state: Louisiana
city: Covington
country: United States
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state: Louisiana
city: Duluth
country: United States
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state: Minnesota
city: Rochester
country: United States
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state: Minnesota
city: Hannibal
country: United States
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state: Missouri
city: Lincoln
country: United States
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state: Nebraska
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Clifton Park
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Canton
country: United States
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state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Maumee
country: United States
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state: Ohio
city: Tulsa
country: United States
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state: Oklahoma
city: Portland
country: United States
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city: Salem
country: United States
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city: Philadelphia
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city: Philadelphia
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city: Philadelphia
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city: York
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city: Watertown
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state: South Dakota
city: Memphis
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city: Dallas
country: United States
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state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Houston
country: United States
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city: Houston
country: United States
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city: Irving
country: United States
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state: Virginia
city: Henrico
country: United States
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state: Virginia
city: Norfolk
country: United States
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state: Virginia
city: Renton
country: United States
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state: Washington
city: Spokane
country: United States
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city: Tacoma
country: United States
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state: Washington
city: Appleton
country: United States
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state: Wisconsin
city: La Crosse
country: United States
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state: Wisconsin
city: Graz
country: Austria
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city: Rankweil
country: Austria
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city: Wien
country: Austria
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city: Wien
country: Austria
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city: Blumenau
country: Brazil
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city: Florianópolis
country: Brazil
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city: Fortaleza
country: Brazil
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city: Londrina
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Sao Paulo
country: Brazil
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country: Brazil
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city: Taubaté
country: Brazil
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city: Vitoria
country: Brazil
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Varna
country: Bulgaria
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city: Saint John
country: Canada
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state: New Brunswick
city: Brampton
country: Canada
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state: Ontario
city: Kitchener
country: Canada
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city: Newmarket
country: Canada
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state: Ontario
city: Sudbury
country: Canada
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state: Ontario
city: Montreal
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: St-Jerome
country: Canada
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state: Quebec
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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city: Chengdu
country: China
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city: Chongqing
country: China
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city: Guangzhou
country: China
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city: Guangzhou
country: China
facility: Research Site
city: Hefei
country: China
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city: Jinan
country: China
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city: Kunming
country: China
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city: Lanzhou
country: China
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city: Liuzhou
country: China
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city: Shandong
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shantou
country: China
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city: Shenyang
country: China
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city: Shenzhen
country: China
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city: Taiyuan
country: China
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city: Tianjin
country: China
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city: Wenzhou
country: China
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city: Wuhan
country: China
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city: Wuhan
country: China
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city: Xiamen
country: China
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city: Yangzhou
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: Brest
country: France
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city: Creteil
country: France
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city: Gleize
country: France
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city: Montpellier
country: France
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city: Nimes
country: France
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city: Paris CEDEX 14
country: France
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city: Paris
country: France
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city: Rouen
country: France
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city: Saint-Quentin
country: France
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city: Strasbourg Cedex
country: France
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city: Toulon Cedex 9
country: France
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city: Toulouse
country: France
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city: Tours
country: France
facility: Research Site
city: Bad Berka
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt A. Main
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Gütersloh
country: Germany
facility: Research Site
city: Hamburg
country: Germany
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city: Kassel
country: Germany
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city: Kiel
country: Germany
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city: Koblenz
country: Germany
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city: Minden
country: Germany
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city: Rosenheim
country: Germany
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country: Germany
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city: Würzburg
country: Germany
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city: Athens
country: Greece
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city: Athens
country: Greece
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city: Athens
country: Greece
facility: Research Site
city: Peiraias
country: Greece
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city: Thessaloniki
country: Greece
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city: Thessaloniki
country: Greece
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city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyöngyös - Mátraháza
country: Hungary
facility: Research Site
city: Kaposvár
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szekszárd
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Calicut
country: India
facility: Research Site
city: Delhi
country: India
facility: Research Site
city: Delhi
country: India
facility: Research Site
city: Jaipur
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Madurai
country: India
facility: Research Site
city: Puducherry
country: India
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Lecco
country: Italy
facility: Research Site
city: Messina
country: Italy
facility: Research Site
city: Napoli
country: Italy
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city: Orbassano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Peschiera Del Garda
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
facility: Research Site
city: Hirosaki-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Jinju-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: Seoul
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: Cdmx
country: Mexico
facility: Research Site
city: Del. Cuauhtemoc
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: San Luis Potosí
country: Mexico
facility: Research Site
city: Arequipa
country: Peru
facility: Research Site
city: Concepción
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Bystra
country: Poland
facility: Research Site
city: Grudziądz
country: Poland
facility: Research Site
city: Kielce
country: Poland
facility: Research Site
city: Koszalin
country: Poland
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: Racibórz
country: Poland
facility: Research Site
city: Radom
country: Poland
facility: Research Site
city: Siedlce
country: Poland
facility: Research Site
city: Las Palmas de Gran Canaria
country: Spain
facility: Research Site
city: Lugo
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Gävle
country: Sweden
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Cheltenham
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
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city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
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city: Middlesborough
country: United Kingdom
facility: Research Site
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Perelman Center for Advanced Medicine
name: Charu Aggarwal
role: STUDY_CHAIR
References: