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NCT06921785PHASE3Recruiting

Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma

AstraZeneca

Start Date

5/6/2025

Completion Date

3/15/2030

Summary

This is a Phase III, randomised, open-label, sponsor-blinded, 3-arm, multicentre, global study assessing the efficacy and safety of rilvegostomig in combination with bevacizumab with or without tremelimumab compared to atezolizumab in combination with bevacizumab. This study will be conducted in participants with advanced HCC who are not amenable to curative therapy or locoregional therapy

Detailed Description

The purpose of this study is to assess the efficacy and tolerability of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line treatment in participants with advanced HCC. The study comprises 2 parts - a safety lead-in and a randomised period. Prior to the start of the randomised period of the study, a single-arm safety lead-in period will be applied to evaluate the safety and tolerability of rilvegostomig in combination with bevacizumab and tremelimumab.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Locally advanced or metastatic and/or unresectable HCC * WHO/ECOG performance status of 0 or 1 * BCLC stage B (that is not eligible for locoregional therapy) or stage C. * Child-Pugh Score class A * At least one measurable target lesion * Participants with active HBV infection must receive antiviral therapy for a minimum of 14 days prior to randomization to show evidence of HBV stabilization or signs of viral response. * Participants with active HCV infection must be well controlled. Participants co-infected with HBV and HCV are not eligible. * Adequate organ and bone marrow function measured during the screening period. * Adequate organ and bone marrow function measured during the screening period * Must not have received prior systemic therapy for intermediate, advanced, or metastatic HCC. * Disease that is not amenable to curative surgical and/or locoregional therapies. For participants who received locoregional therapy for HCC, locoregional therapy must have been completed ≥ 28 days prior to the baseline scan for the current study. Exclusion Criteria: Medical condition * Any evidence of uncontrolled intercurrent diseases * Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment * History of another primary malignancy * Persistent toxicities caused by previous anti-cancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline. * Clinically meaningful ascites, pleural effusion, or pericardial effusion requiring non-pharmacologic intervention to maintain symptomatic control within 6 months prior to the first scheduled dose. * History of active primary immunodeficiency or active infection * History of hepatic encephalopathy * Current or recent (within 10 days of first dose of study treatment) use of aspirin (≥ 325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol * Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purposes is ineligible * History of significant bleeding disorders, vasculitis, or a significant bleeding episode from the GI tract within 6 months prior to study randomization. * Participants with untreated or incompletely treated varices with bleeding or high-risk (red wale signs or other high-risk factors) for bleeding. HCC related * Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. * Central nervous system metastases or spinal cord compression (including asymptomatic and adequately treated disease) * Prior treatment with anti-CTLA-4 and/or anti-TIGIT. * Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment

Interventions

DRUG

Tremelimumab

DRUG

Rilvegostomig

DRUG

Bevacizumab

DRUG

Atezolizumab

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Conditions

Hepatocellular Carcinoma

Locations

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Phoenix, Arizona 85054

United States

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Tucson, Arizona 85719

United States

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Los Angeles, California 90095

United States

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Palo Alto, California 94304

United States

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New Haven, Connecticut 06520

United States

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Newark, Delaware 19713

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Jacksonville, Florida 32224

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Atlanta, Georgia 30318

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Atlanta, Georgia 30322

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Honolulu, Hawaii 96813

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Chicago, Illinois 60637

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Indianapolis, Indiana 46202

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Shreveport, Louisiana 71103

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Detroit, Michigan 48202

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Grand Rapids, Michigan 49503

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Rochester, Minnesota 55905

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St Louis, Missouri 63110

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New Brunswick, New Jersey 08901

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New York, New York 10029

United States

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New York, New York 10032

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New York, New York 10065

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Cleveland, Ohio 44195

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Oklahoma City, Oklahoma 73104

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Philadelphia, Pennsylvania 19107

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Pittsburgh, Pennsylvania 15232

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Amarillo, Texas 79124

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Austin, Texas 78705

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Dallas, Texas 75390

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Houston, Texas 77030

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San Antonio, Texas 78240

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Tyler, Texas 75702

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Arlington, Virginia 22201

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Salem, Virginia 24153

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Seattle, Washington 98101

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Milwaukee, Wisconsin 53226

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Auchenflower, 4066

Australia

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Camperdown, 2050

Australia

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Clayton, 3168

Australia

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Heidelberg, 3084

Australia

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Shatin, 00000

Australia

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Barretos, 14784-400

Brazil

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Porto Alegre, 91350-200

Brazil

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Santa Maria, 97015-450

Brazil

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São Paulo, 04014-002

Brazil

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São Paulo, 05652-9000

Brazil

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Vitória, 29043-272

Brazil

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Edmonton, Alberta T6G 1Z2

Canada

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Halifax, Nova Scotia B3H 1V7

Canada

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Barrie, Ontario L4M 6M2

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Brampton, Ontario L6R 3J7

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Cambridge, Ontario N1R 3G2

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Ottawa, Ontario K1H 8L6

Canada

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Toronto, Ontario M5G 1X6

Canada

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Montreal, Quebec H2X 0A9

Canada

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Québec, Quebec G1J 1Z4

Canada

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Beijing, 100034

China

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Beijing, 100142

China

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Beijing, CN-100730

China

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Changchun, 130021

China

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Changsha, 410013

China

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Chengdu, 610041

China

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Chifeng, 024000

China

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Chongqing, 400010

China

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Deyang, 618000

China

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Fuzhou, 350005

China

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Guangzhou, 510060

China

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Guangzhou, 510515

China

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Guiyang, 550002

China

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Harbin, 150081

China

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Hefei, 230022

China

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Hohhot, 010020

China

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Kunming, 650118

China

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Linyi, 276000

China

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Lishui, 323000

China

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Luoyang, 471000

China

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Nanchang, 330008

China

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Nanchang, 330029

China

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Nanjing, 210029

China

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Nanning, 530021

China

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Nantong, 226361

China

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Neijiang, 641100

China

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Shandong,

China

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Shanghai, 201114

China

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Shenyang, 110004

China

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Shenyang, 110042

China

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Weifang, 261000

China

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Wenzhou, 325000

China

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Wuhan, 430079

China

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Xi'an, 710100

China

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Zhengzhou, 450008

China

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Clichy, 92118

France

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Lille, 59000

France

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Lyon, 69317

France

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Montpellier, 34090

France

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Nantes, 44093

France

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Nice, 06200

France

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Pessac, 33604

France

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Rennes, 35000

France

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Toulouse, 31059

France

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Aachen, 52074

Germany

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Berlin, 13353

Germany

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Bonn, 53127

Germany

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Dortmund, 44137

Germany

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Dresden, 01307

Germany

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Essen, 45122

Germany

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Frankfurt, 60488

Germany

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Frankfurt, 60590

Germany

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Göttingen, 37075

Germany

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Hamburg, 20246

Germany

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Hanover, 30623

Germany

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Leipzig, 4103

Germany

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Lübeck, 23538

Germany

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Magdeburg, 39120

Germany

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Moers, 47441

Germany

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München, 81377

Germany

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Regensburg, 93053

Germany

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Ulm, 89081

Germany

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Hong Kong, 999077

Hong Kong

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Shatin, 00000

Hong Kong

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Ahmedabad, 380058

India

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Bangalore, 560027

India

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Binnāguri, 734015

India

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Dehradun, 248016

India

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Delhi, 110029

India

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Hyderabad, 500032

India

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Mumbai, 400012

India

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Nashik, 422011

India

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Vadodara, 391760

India

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Bologna, 40138

Italy

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Milan, 20132

Italy

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Milan, 20162

Italy

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Palermo, 90127

Italy

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Perugia, 06132

Italy

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Pisa, 56126

Italy

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Roma, 00168

Italy

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Rozzano, 20089

Italy

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Bunkyō City, 113-8655

Japan

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Chiba, 260-8677

Japan

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Fukuoka, 811-1395

Japan

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Hiroshima, 734-8530

Japan

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Hiroshima, 734-8551

Japan

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Iizuka-shi, 820-8505

Japan

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Kashiwa, 227-8577

Japan

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Kita-gun, 761-0793

Japan

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Kobe, 650-0017

Japan

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Kōtoku, 135-8550

Japan

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Kumamoto, 860-8556

Japan

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Kurume-shi, 830-0011

Japan

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Kyoto, 602-8566

Japan

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Matsuyama, 790-0024

Japan

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Mitaka-shi, 181-8611

Japan

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Morioka, 028-3695

Japan

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Musashino-shi, 180-8610

Japan

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Nagoya, 464-8681

Japan

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Okayama, 700-8558

Japan

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Osaka, 541-8567

Japan

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Osakasayama-shi, 589-8511

Japan

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Saga, 849-8501

Japan

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Sapporo, 006-8555

Japan

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Sendai, 981-0914

Japan

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Suita-shi, 565-0871

Japan

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Tokyo, 104-0045

Japan

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Toyoake-shi, 470-1192

Japan

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Tsu, 514-8507

Japan

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Yokohama, 232-0024

Japan

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Yokohama, 241-8515

Japan

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Amsterdam, 1081HV

Netherlands

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Groningen, 9700 RB

Netherlands

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Maastricht, 6229 HX

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Rotterdam, 3015 GD

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Utrecht, 3584 CX

Netherlands

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Gdansk, 80-214

Poland

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Koszalin, 75-581

Poland

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Lublin, 20-090

Poland

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Olsztyn, 10-228

Poland

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Warsaw, 02-034

Poland

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Busan, 48108

South Korea

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Goyang-si, 410-769

South Korea

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Gyeonggi-do, 13620

South Korea

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Seongnam-si, 463-712

South Korea

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Seoul, 03080

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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Barcelona, 08035

Spain

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Barcelona, 08036

Spain

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Madrid, 28007

Spain

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Madrid, 28027

Spain

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Madrid, 28040

Spain

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Santander, 39008

Spain

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Changhua, 500

Taiwan

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Kaohsiung City, 83301

Taiwan

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Taichung, 40447

Taiwan

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Tainan, 70403

Taiwan

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Tainan County, 71044

Taiwan

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Taipei, 10002

Taiwan

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Taipei, 112

Taiwan

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Taoyuan, 333

Taiwan

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Bangkok, 10210

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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Hat Yai, 90110

Thailand

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Muang, 40002

Thailand

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Ubonratchathani, 34000

Thailand

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Altındağ, 06230

Turkey (Türkiye)

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Ankara, 06530

Turkey (Türkiye)

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Erzurum, 25240

Turkey (Türkiye)

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Istanbul, 34180

Turkey (Türkiye)

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Izmir, 35100

Turkey (Türkiye)

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Cambridge, CB2 0QQ

United Kingdom

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Leeds, LS9 7TF

United Kingdom

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London, NW3 2QG

United Kingdom

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London, SE5 9RS

United Kingdom

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London, W12 0HS

United Kingdom

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Manchester, M20 4BX

United Kingdom

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Hanoi, 100000

Vietnam

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Hanoi, 100000

Vietnam

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Ho Chi Minh City, 700000

Vietnam

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Ho Chi Minh City, 700000

Vietnam