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NCT07218809PHASE3Recruiting

AZD5335 vs. Mirvetuximab Soravtansine in FRα-high and AZD5335 vs. Chemotherapy in FRα-low Platinum-resistant Ovarian Cancer

AstraZeneca

Start Date

12/29/2025

Completion Date

12/27/2029

Summary

The intention of the study is to demonstrate superiority of AZD5335 versus standard of care by assessment of progression-free survival (PFS) in women with high-grade, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, expressing high or low FRα levels.

Detailed Description

Approximately 1100 adult participants will be enrolled after central FRα testing into two independent cohorts (about 550 FRα-high and 550 FRα-low) and randomized 1:1 within each cohort to receive AZD5335 or the relevant standard of care (mirvetuximab soravtansine in FRα-high; investigator's choice single-agent chemotherapy in FRα-low). Participants will remain on assigned treatment and undergo regular tumor evaluations per RECIST v1.1 until disease progression or another reason for treatment discontinuation. All participants will be followed for overall survival. An independent data monitoring committee (IDMC) of external experts will periodically review unblinded safety and interim efficacy to confirm participant safety and study integrity.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion criteria * Participants with confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer. * Participants must have platinum-resistant disease: * Participants who have only had one prior line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between \> 3 months and ≤ 6 months after the date of the last dose of platinum. * Participants who have received 2 or 3 lines of platinum therapy must have progressed ≤ 6 months after the date of the last dose of platinum. * Participants must have radiologically progressed on or after their most recent line of therapy. * Participants must have received at least one, but no more than 3, prior systemic lines of anti-cancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment * Participants with documented BRCA mutation (germline and/or somatic) must have received prior PARPi if the participant is eligible per approved label and standard-of-care institutional guidelines, except in cases of documented contraindication, precaution or intolerance. * Provision of an FFPE tumour tissue sample Key Exclusion criteria * Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumours containing any of the above histologies, or low-grade or borderline ovarian tumour. * Primary platinum-refractory disease, defined as disease that did not respond to or has progressed ≤ 3 months after the last dose of first line platinum-containing chemotherapy. * Participants with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring * Current signs, symptoms, or clinical investigations consistent with bowel obstruction, including sub-occlusive disease. * Participant has non-infectious ILD/pneumonitis or has a history of non-infectious ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Prior treatment with any FRα-targeted therapy, including MIRV, or any TOP1i ADC. * Major surgical procedure within 4 weeks of the first dose of study intervention

Interventions

DRUG

AZD5335

DRUG

Mirvetuximab Soravtansine (MIRV)

DRUG

Paclitaxel

DRUG

Pegylated liposomal Doxorubicin (PLD)

DRUG

Topotecan

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Conditions

Epithelial Ovarian Cancer

Locations

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Birmingham, Alabama 35223

United States

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Little Rock, Arkansas 72205

United States

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La Jolla, California 92037

United States

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Washington D.C., District of Columbia 20010

United States

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Fort Lauderdale, Florida 33316

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Gainesville, Florida 32608

United States

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Jupiter, Florida 33458

United States

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Miami, Florida 33176

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Weston, Florida 33331

United States

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Chicago, Illinois 60612

United States

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Evanston, Illinois 60201

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Peoria, Illinois 61637

United States

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Urbana, Illinois 61801

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Fort Wayne, Indiana 46845

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Indianapolis, Indiana 46202

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Louisville, Kentucky 40241

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Towson, Maryland 21204

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Burlington, Massachusetts 01805

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Worcester, Massachusetts 01655

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Minneapolis, Minnesota 55404

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Springfield, Missouri 65807

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Billings, Montana 59106

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Omaha, Nebraska 68114

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Las Vegas, Nevada 89106

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Lebanon, New Hampshire 03756

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Camden, New Jersey 08103

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The Bronx, New York 10461

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Chapel Hill, North Carolina 27599

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Blue Ash, Ohio 45242

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Dayton, Ohio 45459

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Sylvania, Ohio 43560

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Portland, Oregon 97213

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York, Pennsylvania 17403

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Germantown, Tennessee 38138

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San Antonio, Texas 78229

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Tyler, Texas 75702

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Salt Lake City, Utah 84106

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Fairfax, Virginia 22031

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Roanoke, Virginia 24016

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Seattle, Washington 98104

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Adelaide, 5037

Australia

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Auchenflower, 4066

Australia

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Campbelltown, 2560

Australia

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Camperdown, 2050

Australia

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Clayton, 3168

Australia

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Cudgen, 2487

Australia

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Garran, 2605

Australia

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Gosford, 2250

Australia

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Heidelberg, 3084

Australia

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Kogarah, 2217

Australia

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Melbourne, 3000

Australia

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Richmond, 3121

Australia

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St Leonards, 2065

Australia

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Waratah, 2298

Australia

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Charleroi, 6060

Belgium

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Edegem, 2650

Belgium

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Ghent, 9000

Belgium

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Leuven, 3000

Belgium

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Libramont-Chevigny, 6800

Belgium

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Namur, 5000

Belgium

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Barretos, 14784-400

Brazil

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Bela Vista, 1317

Brazil

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Curitiba, 81520-060

Brazil

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Goiânia, 74110-060

Brazil

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Natal, 59075-740

Brazil

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Porto Alegre, 90020-090

Brazil

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Porto Alegre, 90035-903

Brazil

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Porto Alegre, 90610-000

Brazil

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Porto Alegre, 91350200

Brazil

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Porto Velho, 76834-899

Brazil

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Rio de Janeiro, 20230-130

Brazil

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São José do Rio Preto, 15090-000

Brazil

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São Paulo, 01401-002

Brazil

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São Paulo, 01409-902

Brazil

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Edmonton, Alberta T6G 1Z2

Canada

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Hamilton, Ontario L8V 5C2

Canada

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Kingston, Ontario K7L 2V7

Canada

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Montreal, Quebec H1T 2M4

Canada

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Montreal, Quebec H3T 1E2

Canada

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Montreal, Quebec H4A 3J1

Canada

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Québec, G1G 5X1

Canada

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Port Montt, 5480000

Chile

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Providencia, 7510032

Chile

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Santiago, 7500587

Chile

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Santiago, 7500653

Chile

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Santiago, 7520426

Chile

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Santiago, 8330032

Chile

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Santiago, 8331143

Chile

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Santiago, 8420383

Chile

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Viña del Mar, 2520000

Chile

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Beijing, 100021

China

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Beijing, 100142

China

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Beijing, 102600

China

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Bengbu, 233004

China

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Changchun, 130012

China

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Changsha, 410008

China

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Changsha, 410013

China

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Chengdu, 610041

China

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Chongqing, 400030

China

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Fuzhou, 350011

China

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Guangzhou, 510000

China

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Guangzhou, 510060

China

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Guangzhou, 510080

China

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Hangzhou, 310003

China

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Hangzhou, 310006

China

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Hangzhou, 310022

China

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Harbin, 150049

China

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Jinan, 250012

China

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Jinan, 250117

China

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Lanzhou, 730000

China

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Linyi, 276000

China

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Nanchang, 330029

China

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Nanjing, 2100008

China

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Nanjing, 210009

China

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Nanning, 530021

China

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Shanghai, 200025

China

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Shanghai, 200032

China

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Shenyang, 110004

China

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Shenyang, 110042

China

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Shijiazhuang, 050020

China

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Taiyuan, 030000

China

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Tianjin, 300060

China

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Wuhan, 430022

China

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Wuhan, 430030

China

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Wuhan, 430079

China

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Xi'an, 710061

China

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Zhanjiang, 524001

China

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Zhengzhou, 450008

China

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Zhengzhou, 450052

China

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Brno, 625 00

Czechia

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Hradec Králové, 500 05

Czechia

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Nový Jičín, 741 01

Czechia

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Olomouc, 77900

Czechia

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Prague, 12808

Czechia

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Prague, 150 06

Czechia

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Prague, 18000

Czechia

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Aalborg, 9000

Denmark

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Aarhus, 8200

Denmark

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Odense, 5000

Denmark

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Vejle, 7100

Denmark

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Amiens, 80054

France

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Avignon, 84000

France

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Nîmes, 30029

France

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Paris, 75005

France

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Pau, 64046

France

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Pierre-Bénite, 69310

France

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Plerin SUR MER, 22190

France

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Reims, 51056

France

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Saint-Herblain, 44805

France

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Saint-Priest-en-Jarez, 42271

France

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Toulouse, 31300

France

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Tours, 37044

France

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Berlin, 13353

Germany

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Bonn, 53127

Germany

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Detmold, 32756

Germany

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Dresden, 01307

Germany

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Düsseldorf, 40225

Germany

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Essen, 45130

Germany

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Essen, 45147

Germany

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Frankfurt am Main, 60487

Germany

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Hamburg, 20246

Germany

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Hamburg, 22457

Germany

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Hanover, 30625

Germany

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Leipzig, 4103

Germany

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Mannheim, 68167

Germany

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Schwäbisch Hall, 74523

Germany

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Tübingen, 72076

Germany

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Ulm, 89075

Germany

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Wiesbaden, 65199

Germany

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Athens, 11528

Greece

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Athens, 12462

Greece

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Athens, 14564

Greece

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Athens, 15123

Greece

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Kalamata, 24100

Greece

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Pátrai, 26332

Greece

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Rio, 26504

Greece

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Thessaloniki, 55236

Greece

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Bhubaneswar, 751007

India

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Chennai, 600113

India

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Delhi, 110029

India

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Dhanvantari Nagar, 605006

India

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Kolkata, 700017

India

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Nagpur, 440001

India

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Nashik, 422 009

India

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Surat, 395002

India

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Tiruchirappalli, 620008

India

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Cork, T12 DV56

Ireland

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Dublin, 7

Ireland

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Dublin, D08 NHY1

Ireland

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Dublin, DO4YN63

Ireland

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Waterford, X91 ER8E

Ireland

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Afula, 1834111

Israel

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Beersheba, 84101

Israel

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Hadera, 38100

Israel

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Haifa, 3109601

Israel

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Haifa, 34362

Israel

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Holon, 5822012

Israel

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Jerusalem, 00000

Israel

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Jerusalem, 91031

Israel

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Kfar Saba, 4428164

Israel

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Nahariya, 22100

Israel

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Ramat Gan, 52621

Israel

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Sofia, 1680

Israel

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Tel Aviv, 64239

Israel

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Brescia, 25123

Italy

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Catania, 95126

Italy

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Florence, 50134

Italy

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Lecco, 23900

Italy

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Milan, 20133

Italy

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Milan, 20141

Italy

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Milan, 20159

Italy

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Milan, 20162

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Naples, 80131

Italy

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Parma, 43126

Italy

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Pisa, 56126

Italy

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Roma, 00161

Italy

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Roma, 00168

Italy

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Torino, 10100

Italy

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Akashi-shi, 673-8558

Japan

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Chūōku, 104-0045

Japan

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Hidaka-shi, 350-1298

Japan

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Kashiwa, 227-8577

Japan

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Kobe, 650-0047

Japan

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Kōtoku, 135-8550

Japan

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Kurume-shi, 830-0011

Japan

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Nagoya, 464-8681

Japan

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Niigata, 951-8566

Japan

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Okayama, 700-8558

Japan

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Osaka, 541-8567

Japan

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Sagamihara-shi, 252-0375

Japan

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Sapporo, 003-0804

Japan

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Sendai, 980-8574

Japan

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Shinjuku-ku, 160-0023

Japan

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Shinjuku-ku, 160-8582

Japan

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Shiwa-gun, 028-3694

Japan

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Sunto-gun, 411-8777

Japan

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Toon-Shi, 791-0295

Japan

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Tsu, 514-8507

Japan

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Busan, 49241

South Korea

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Daegu, 42601

South Korea

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Goyang-si, 10408

South Korea

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Seongnam-si, 13620

South Korea

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Seoul, 03080

South Korea

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Seoul, 03722

South Korea

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Seoul, 06273

South Korea

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Seoul, 06351

South Korea

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Seoul, 08308

South Korea

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Seoul, 5505

South Korea

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Suwon, 16499

South Korea

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Yangsan, 50612

South Korea

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A Coruña, 15006

Spain

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Badalona, 08916

Spain

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Barcelona, 08036

Spain

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Córdoba, 14004

Spain

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Donostia / San Sebastian, 20014

Spain

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Girona, 17007

Spain

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L'Hospitalet de Llobregat, 08908

Spain

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Madrid, 28034

Spain

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Madrid, 28041

Spain

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Valencia, 46010

Spain

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Linköping, 581 85

Sweden

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Lund, 22242

Sweden

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Solna, 171 64

Sweden

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Umeå, 90737

Sweden

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Uppsala, 751 85

Sweden

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Basel, 4031

Switzerland

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Münsterlingen, 8596

Switzerland

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Sankt Gallen, 9007

Switzerland

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Thun, 3600

Switzerland

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Zollikerberg, CH-8125

Switzerland

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Zurich, 8091

Switzerland

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Changhua,

Taiwan

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New Taipei City, 220

Taiwan

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Taichung, 40447

Taiwan

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Taichung, 40705

Taiwan

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Tainan, 704

Taiwan

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Tainan, 73657

Taiwan

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Taipei, 100

Taiwan

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Taipei, 11259

Taiwan

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Taoyuan, 333

Taiwan

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Bangkok, 10210

Thailand

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Bangkok, 10400

Thailand

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Bangkok, 10700

Thailand

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Chiang Mai, 50200

Thailand

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Dusit, 10300

Thailand

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Khon Kaen, 40002

Thailand

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Songkhla, 90110

Thailand

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Barrow in Furness, LA14 4LF

United Kingdom

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Birmingham, B152GW

United Kingdom

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Cambridge, CB2 0QQ

United Kingdom

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Canterbury, CT1 3NG

United Kingdom

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Cardiff, CF15 7QZ

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Edinburgh, EH4 2XU

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Greater London, SW3 6JJ

United Kingdom

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London, EC1A 7BE

United Kingdom

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London, SE1 9RT

United Kingdom

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Nottingham, NG5 1PB

United Kingdom

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Sutton, SM2 5PT

United Kingdom

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Swansea, SA12 7BR

United Kingdom