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NCT07291037PHASE3Recruiting

Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations

AstraZeneca

Start Date

10/31/2025

Completion Date

1/29/2029

Summary

TROPION-Lung17 will measure the efficacy and safety of datopotamab deruxtecan (Dato-DXd) compared with docetaxel in patients with trophoblast cell surface protein 2 (TROP2) positive advanced or metastatic lung cancer without actionable genomic alterations (AGA).

Detailed Description

TROPION-Lung17 is a phase III, 2-arm, randomised, open-label, multicentre study, assessing the efficacy and safety of Dato-DXd compared with docetaxel in participants with previously treated trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA), and to assess the clinical performance of the investigational in vitro diagnostic (IVD) device.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA) at the time of randomisation and meets the criteria for NSCLC: * Participants must have documented negative test results for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) genomic alterations. * Has no known tumour genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition (MET) exon 14 skipping, Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C, human epidermal growth factor receptor 2 (HER2) or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies. * Prospectively assessed trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive. * Documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC. * Participants must have received platinum based chemotherapy (PBC) in combination with anti-programmed death-protein 1 (anti-PD-1)/anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibody (mAb) as the only prior line of therapy or received PBC and anti-PD-1/anti-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy. * Provision of acceptable formalin fixed and paraffin embedded (FFPE) tumour sample for assessment of TROP2. * At least one lesion not previously irradiated that qualifies as a Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) target lesion (TL) at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1. * Adequate bone marrow reserve and organ function within 7 days before randomisation. Exclusion Criteria: * Squamous, mixed NSCLC, or small cell lung cancer (SCLC) histology. * NSCLC disease that is eligible for definitive local therapy alone. * History of another primary malignancy other than NSCLC, except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence. * Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 7 days prior to randomisation. * Clinically significant corneal disease. * Has active or uncontrolled hepatitis B or C virus infection. * Known human immunodeficiency virus (HIV) infection that is not well controlled. * Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals. * History of non-infectious interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. * Severe pulmonary function compromise per Investigator discretion.

Interventions

DRUG

Datopotamab deruxtecan (Dato-DXd)

DRUG

Docetaxel

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Conditions

Non-small Cell Lung Cancer (NSCLC)

Locations

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Chandler, Arizona 85224

United States

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Gilbert, Arizona 85234

United States

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Goodyear, Arizona 85338

United States

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Duarte, California 91010

United States

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Irvine, California 92618

United States

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La Jolla, California 92093

United States

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Loma Linda, California 92350

United States

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Los Angeles, California 90095

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San Diego, California 92123

United States

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Grand Junction, Colorado 81501

United States

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Wheat Ridge, Colorado 80033

United States

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Newark, Delaware 19713

United States

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Washington D.C., District of Columbia 20037

United States

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Fort Myers, Florida 33901

United States

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Jacksonville, Florida 32224

United States

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St. Petersburg, Florida 33709

United States

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Tampa, Florida 33612

United States

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West Palm Beach, Florida 33401

United States

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Marietta, Georgia 30060

United States

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Newnan, Georgia 30265

United States

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Chicago, Illinois 60612

United States

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Chicago, Illinois 60637

United States

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Niles, Illinois 60714

United States

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Zion, Illinois 60099

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Louisville, Kentucky 40207

United States

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South Portland, Maine 04106

United States

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Baltimore, Maryland 21201

United States

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Brandywine, Maryland 20613

United States

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Boston, Massachusetts 02215

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Detroit, Michigan 48202

United States

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Rochester, Minnesota 55905

United States

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Bridgeton, Missouri 63044

United States

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Columbia, Missouri 65212

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Lincoln, Nebraska 68516

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Albuquerque, New Mexico 87109

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East Syracuse, New York 13057

United States

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Portland, Oregon 97239

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Hershey, Pennsylvania 17033

United States

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Lancaster, Pennsylvania 17601

United States

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Greenville, South Carolina 29607

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Memphis, Tennessee 38120

United States

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Austin, Texas 78745

United States

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Denton, Texas 76201

United States

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Plano, Texas 75075

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Charlottesville, Virginia 22908

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Fairfax, Virginia 22031

United States

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Williamsburg, Virginia 23188

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Tacoma, Washington 98405

United States

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Morgantown, West Virginia 26506

United States

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Eau Claire, Wisconsin 54703

United States

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Gosford, 2250

Australia

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Kogarah, 2217

Australia

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South Brisbane, 4101

Australia

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St Albans, 3021

Australia

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Wollongong, 2500

Australia

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Graz, 8036

Austria

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Linz, 4021

Austria

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Rankweil, 6830

Austria

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Vienna, 1140

Austria

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Vienna, 1210

Austria

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Hasselt, 3500

Belgium

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La Louvière, 7100

Belgium

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Libramont-Chevigny, 6800

Belgium

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Sint-Niklaas, 9100

Belgium

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Yvoir, 5530

Belgium

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Porto Alegre, 90610-000

Brazil

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Porto Alegre, 91350-200

Brazil

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Salvador, 40170-110

Brazil

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São Paulo, 01246-000

Brazil

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São Paulo, 01327-001

Brazil

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São Paulo, 05652-900

Brazil

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Vancouver, British Columbia VSZ 4E6

Canada

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Moncton, New Brunswick E1C 6Z8

Canada

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Halifax, Nova Scotia B3H 2Y9

Canada

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Brampton, Ontario L6R 3J7

Canada

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Hamilton, Ontario L8V 1C3

Canada

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Toronto, Ontario M5G 1X6

Canada

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Beijing, 100034

China

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Beijing, 100142

China

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Beijing, 101149

China

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Changchun, 130000

China

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Changsha, 410013

China

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Chengdu, 610041

China

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Chengdu, 610072

China

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Chongqing, 400030

China

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Fuzhou, 350011

China

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Guangzhou, 510080

China

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Hangzhou, 310022

China

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Harbin, 150081

China

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Hefei, 230610

China

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Jiamusi, 154007

China

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Jinan, 250117

China

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Nanchang, 330006

China

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Nanjing, 2100008

China

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Shanghai, 200030

China

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Shanghai, 200032

China

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Shanghai, 200433

China

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Shantou, 515041

China

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Shenyang, 110004

China

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Tianjin, 300050

China

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Wuhan, 430030

China

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Wuhan, 430060

China

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Xuzhou, 221009

China

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Zhengzhou, 450008

China

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Zhengzhou, 450052

China

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Boulogne-Billancourt, 92104

France

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Lyon, 69008

France

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Marseille, 13915

France

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Saint-Herblain, 44800

France

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Toulouse, 31400

France

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Bad Saarow, 15526

Germany

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Bielefeld, 33611

Germany

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Bonn, 53127

Germany

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Cologne, 51109

Germany

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Essen, 45147

Germany

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Frankfurt, 60488

Germany

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Freiburg im Breisgau, 79106

Germany

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Gauting, 82131

Germany

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Hamburg, 20251

Germany

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Heidelberg, 69126

Germany

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Krefeld, 47805

Germany

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Minden, 32429

Germany

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Oldenburg, 26121

Germany

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Stuttgart, 70174

Germany

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Troisdorf, 53840

Germany

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Velbert, 42551

Germany

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Budapest, 1083

Hungary

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Budapest, 1121

Hungary

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Budapest, 1122

Hungary

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Budapest, 1145

Hungary

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Debrecen, 4032

Hungary

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Gyöngyös - Mátraháza, 3200

Hungary

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Győr, 9024

Hungary

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Gyula, 5700

Hungary

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Kecskemét, 6000

Hungary

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Szolnok, 5000

Hungary

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Törökbálint, 2045

Hungary

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Bangalore, 560027

India

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Kolkata, 700016

India

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Mumbai, 400012

India

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Nashik, 422011

India

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New Delhi, 11029

India

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Milan, 20141

Italy

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Milan, 20162

Italy

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Monza, 20052

Italy

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Orbassano, 10043

Italy

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Padova, 35128

Italy

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Rozzano, 20089

Italy

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Chūōku, 104-0045

Japan

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Fukuoka, 812-8582

Japan

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Hiroshima, 734-8551

Japan

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Iwakuni-shi, 740-8510

Japan

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Kashiwa, 277-8577

Japan

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Kawasaki-shi, 216-8511

Japan

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Kyoto, 612-8555

Japan

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Matsuyama, 791-0280

Japan

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Nagoya, 464-8681

Japan

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Niigata, 951-8566

Japan

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Osaka, 541-8567

Japan

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Osakasayama-shi, 589-8511

Japan

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Sendai, 981-0914

Japan

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Sunto-gun, 411-8777

Japan

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Yokohama, 241-8515

Japan

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Lodz, 93-338

Poland

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Olsztyn, 10-357

Poland

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Poznan, 60-569

Poland

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Warsaw, 02-781

Poland

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Goyang-si, 10408

South Korea

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Incheon, 21565

South Korea

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Seoul, 03722

South Korea

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Seoul, 06351

South Korea

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Seoul, 5505

South Korea

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Suwon, 16247

South Korea

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A Coruña, 15009

Spain

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Barcelona, 8035

Spain

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L'Hospitalet de Llobregat, 08908

Spain

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Madrid, 28041

Spain

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Málaga, 29010

Spain

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Seville, 41009

Spain

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Zaragoza, 50009

Spain

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Kaohsiung City, 80756

Taiwan

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Taichung, 40705

Taiwan

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Tainan, 73657

Taiwan

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Taipei, 10002

Taiwan

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Taipei, 11217

Taiwan

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Taipei, 11490

Taiwan

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Taoyuan, 333

Taiwan

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Bangkok, 10210

Thailand

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Bangkok, 10300

Thailand

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Bangkok, 10700

Thailand

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Hat Yai, 90110

Thailand

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Muang, 50200

Thailand

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Ankara, 06530

Turkey (Türkiye)

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Istanbul, 32098

Turkey (Türkiye)

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Huddersfield, HD3 3EA

United Kingdom

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London, SE1 9RT

United Kingdom

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London, SW10 9NH

United Kingdom

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London, SW170QT

United Kingdom

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Maidstone, ME16 9QQ

United Kingdom

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Norwich, NR4 7UY

United Kingdom

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Stoke-on-Trent, ST4 6QG

United Kingdom

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Hanoi, 100000

Vietnam

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Ho Chi Minh City, 70 449

Vietnam

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Ho Chi Minh City, 700000

Vietnam

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Vinh, 460000

Vietnam