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NCT06380751PHASE3Recruiting

Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer

AstraZeneca

Start Date

8/1/2024

Completion Date

12/30/2031

Summary

The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients with BRCA1, BRCA2, or PALB2m, HR-positive, HER2-negative (defined as IHC 0, 1+, 2+/ ISH non-amplified) advanced breast cancer

Detailed Description

Approximately 4680 participants will be screened to achieve approximately 788 participants randomised to study intervention. Participants will be randomised in a 2:2:1:2 ratio to one of the following intervention groups: * Arm 1: saruparib (AZD5305) plus camizestrant * Arm 2: Physician's choice CDK4/6i plus physician's choice ET * Arm 3: Physician's choice CDK4/6i plus camizestrant * Arm 4: Saruparib (AZD5305) plus physician's choice ET Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Adult females, pre/peri-menopausal and/or post-menopausal, and adult males * Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer * Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease * ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks * FFPE tumour tissue from each participant * Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2 * Adequate organ and marrow function Exclusion Criteria: * Participants with history of MDS/AML or with features suggestive of MDS/AML * Participants with any known predisposition to bleeding * Any history of persisting severe cytopenia * Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections * Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection * History of another primary malignancy * Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy excluding alopecia * Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease * Evidence of active and uncontrolled hepatitis B and/or hepatitis C * Evidence of active and uncontrolled HIV infection * Active tuberculosis infection * Cardiac criteria, including history of arrythmia and cardiovascular disease * Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions * Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study * Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study treatment * Prior treatment with systemic anti-cancer therapy for locoregionally recurrent or metastatic disease is not permitted, apart from treatment with ET for up to 28 days total before randomisation * Prior treatment within 28 days with blood product support or growth factor support * Any systemic concurrent anti-cancer treatment * Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives of randomisation: 1. Strong and moderate CYP3A4 inducers/inhibitors 2. Sensitive CYP2B6 substrates 3. Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin. * Concomitant use of drugs that are known to prolong QT and have a known risk of TdP * Systemic use of atropine * The following exclusion criteria apply to treatments administered for early breast cancer: 1. Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy 2. Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer 3. Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting 4. Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.

Interventions

DRUG

Saruparib (AZD5305)

DRUG

Camizestrant

DRUG

Abemaciclib

DRUG

Ribociclib

DRUG

Palbociclib

DRUG

Fulvestrant

DRUG

Letrozole

DRUG

Anastrozole

DRUG

Exemestane

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Conditions

Advanced Breast Cancer

Locations

Research Site

Gilbert, Arizona 85234

United States

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Fountain Valley, California 92708

United States

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Glendale, California 91206

United States

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Los Angeles, California 90089

United States

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Newport Beach, California 92663

United States

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Aurora, Colorado 80045

United States

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Grand Junction, Colorado 81501

United States

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Hollywood, Florida 33021

United States

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Jacksonville, Florida 32224

United States

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Orlando, Florida 32806

United States

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Arlington Heights, Illinois 60005

United States

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Chicago, Illinois 60611

United States

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Evanston, Illinois 60201

United States

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Park Ridge, Illinois 60068

United States

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Urbana, Illinois 61801

United States

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Winfield, Illinois 60190

United States

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Indianapolis, Indiana 46227

United States

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Louisville, Kentucky 40207

United States

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Baltimore, Maryland 21201

United States

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Silver Spring, Maryland 20902

United States

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Silver Spring, Maryland 20904

United States

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Boston, Massachusetts 02215

United States

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Dearborn, Michigan 48126

United States

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Detroit, Michigan 48202

United States

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Royal Oak, Michigan 48073

United States

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Royal Oak, Michigan 48073

United States

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Rochester, Minnesota 55905

United States

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Saint Joseph, Missouri 64507

United States

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Springfield, Missouri 65804

United States

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St Louis, Missouri 63110

United States

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Camden, New Jersey 08103

United States

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New Brunswick, New Jersey 08901

United States

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Brooklyn, New York 11220

United States

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Mineola, New York 11501

United States

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New Hyde Park, New York 11042

United States

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New York, New York 10016

United States

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New York, New York 10028

United States

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New York, New York 10065

United States

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Shirley, New York 11967

United States

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Stony Brook, New York 11790

United States

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The Bronx, New York 10469

United States

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Westbury, New York 11590

United States

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Hershey, Pennsylvania 17033

United States

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Philadelphia, Pennsylvania 19104

United States

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Pittsburgh, Pennsylvania 15212

United States

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Pittsburgh, Pennsylvania 15215

United States

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West Columbia, South Carolina 29169

United States

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Chattanooga, Tennessee 37404

United States

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Nashville, Tennessee 37203

United States

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Houston, Texas 77030

United States

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Houston, Texas 77030

United States

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Houston, Texas 77054

United States

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San Antonio, Texas 78240

United States

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Norfolk, Virginia 23502

United States

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Tacoma, Washington 98405

United States

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Morgantown, West Virginia 26506

United States

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Milwaukee, Wisconsin 53215

United States

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Ciudad Autónoma Buenos Aires, 1125

Argentina

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Ciudad de Buenos Aires, 1015

Argentina

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Ciudad de Buenos Aires, C1280AEB

Argentina

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Córdoba, 5008

Argentina

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Rosario, S2000KZE

Argentina

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Salta, A4400EMI

Argentina

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San Miguel de Tucumán, 4000

Argentina

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Darlinghurst, 2010

Australia

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Darlinghurst, 2139

Australia

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Malvern, 3144

Australia

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Melbourne, VIC 3000

Australia

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Graz, 8036

Austria

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Innsbruck, 6020

Austria

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Linz, 4010

Austria

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Vienna, 1090

Austria

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Cachoeira de Itapemirim, 29308-055

Brazil

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Curitiba, 80060-900

Brazil

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Fortaleza, 60336-045

Brazil

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Goiânia, 74000-000

Brazil

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Jaú, 17210-120

Brazil

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Porto Alegre, 91350-200

Brazil

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Ribeirão Preto, 14049-901

Brazil

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Salvador, 41253-190

Brazil

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São Paulo, 01509-900

Brazil

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São Paulo, 03102-002

Brazil

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Plovdiv, 4002

Bulgaria

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Sofia, 1527

Bulgaria

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Stara Zagora, 6003

Bulgaria

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Vratsa, 3000

Bulgaria

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Toronto, Ontario M5G 2M9

Canada

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Greenfield Park, Quebec J4V 2G9

Canada

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Montreal, Quebec H2X 0A9

Canada

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Montreal, Quebec H3T 1E2

Canada

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Montreal, Quebec H4A 3J1

Canada

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Saskatoon, Saskatchewan S7N 4H4

Canada

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Toronto, M4N 3M5

Canada

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Providencia, 7500994

Chile

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Recoleta, 8420391

Chile

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Santiago, 8330034

Chile

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Talca, 3461341

Chile

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Viña del Mar, 2520000

Chile

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Beijing, 100044

China

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Bengbu, 233004

China

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Changchun, 130012

China

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Changchun, 130021

China

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Changsha, 410008

China

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Changsha, 410013

China

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Chengdu, 610000

China

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Chengdu, 610072

China

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Chongqing, 400042

China

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Foshan, 528000

China

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Fuzhou, 350014

China

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Guangzhou, 510060

China

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Guangzhou, 510062

China

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Guangzhou, 510289

China

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Hangzhou, 310016

China

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Hangzhou, 310022

China

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Harbin, 150081

China

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Hefei, 230031

China

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Hohhot, 010017

China

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Jining, 272029

China

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Kunming, 650118

China

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Liuzhou, 545006

China

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Luoyang, 471000

China

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Nanchang, 330006

China

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Nanchang, 330009

China

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Nanjing, 210029

China

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Shandong, 250117

China

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Shanghai, 200025

China

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Shanghai, 200120

China

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Shenyang, 110016

China

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Shijiazhuang, 050000

China

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Tianjin, 300000

China

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Weifang, 261000

China

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Wuhan, 430030

China

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Wuhan, 430040

China

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Wuhan, 430079

China

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Xi'an, 710006

China

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Xi'an, 710061

China

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Xiamen, 361003

China

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Xiangyang, 441000

China

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Xinxiang, 453100

China

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Zhengzhou, 450008

China

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Brno, 656 53

Czechia

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Hořovice, 26831

Czechia

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Hradec Králové, 500 05

Czechia

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Olomouc, 77900

Czechia

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Prague, 120 00

Czechia

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Prague, 180 00

Czechia

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Angers, 49100

France

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Besançon, 25030

France

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Lille, 59000

France

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Lyon, 69373

France

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Marseille, 13273

France

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Paris, 75005

France

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Rouen, 76021

France

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Saint-Herblain, 44805

France

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Toulouse, 31059

France

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Villejuif, 94805

France

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Aachen, 52074

Germany

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Augsburg, 86150

Germany

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Berlin, 13125

Germany

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Cologne, 50937

Germany

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Dessau, 06847

Germany

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Düsseldorf, 40225

Germany

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Erlangen, 91054

Germany

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Göttingen, DE-37099

Germany

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Hamburg, 20357

Germany

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Hanover, 30625

Germany

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Heidelberg, 69120

Germany

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Kiel, 24105

Germany

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Leipzig, 04103

Germany

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Ludwigsburg, 71640

Germany

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München, 81675

Germany

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Münster, 48149

Germany

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Hong Kong, 150001

Hong Kong

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Hong Kong, 999077

Hong Kong

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Budapest, 1062

Hungary

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Budapest, 1082

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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Miskolc, 3526

Hungary

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Zalaegerszeg, 8900

Hungary

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Delhi, 110029

India

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Kolkata, 700160

India

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Lucknow, 226003

India

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Mumbai, 400012

India

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Mumbai, 400052

India

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Mysuru, 570017

India

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Nagpur, 440001

India

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Nashik, 422002

India

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New Delhi, 110085

India

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Surat, 396007

India

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Thiruvananthapuram, 695011

India

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Jerusalem, 9103102

Israel

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Jerusalem, 9112001

Israel

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Petah Tikva, 49100

Israel

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Ramat Gan, 52621

Israel

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Tel Aviv, 64239

Israel

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Bergamo, 24127

Italy

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Bologna, 40138

Italy

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Milan, 20132

Italy

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Milan, 20141

Italy

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Modena, 41124

Italy

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Naples, 80131

Italy

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Padova, 35128

Italy

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Reggio Emilia, 422122

Italy

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Rome, 00168

Italy

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Rozzano, 20089

Italy

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Chiba, 260-8717

Japan

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Hidaka-shi, 350-1298

Japan

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Hirakata-shi, 573-1191

Japan

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Isehara-shi, 259-1193

Japan

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Kagoshima, 892-0833

Japan

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Kashiwa, 227-8577

Japan

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Kōtoku, 135-8550

Japan

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Kumamoto, 860-8556

Japan

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Kyoto, 606-8507

Japan

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Matsuyama, 791-0280

Japan

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Nagoya, 464-8681

Japan

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Nagoya, 466-8560

Japan

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Nagoya, 467-8602

Japan

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Osaka, 541-8567

Japan

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Ota-shi, 373-8550

Japan

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Sapporo, 003-0804

Japan

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Sendai, 980-8574

Japan

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Shinagawa-ku, 142-8666

Japan

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Suita-shi, 565-0871

Japan

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Sunto-gun, 411-8777

Japan

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Takasaki-shi, 370-0829

Japan

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Tsu, 514-8507

Japan

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Yokohama, 241-8515

Japan

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Bandar Puncak Alam, 42300

Malaysia

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Johor Bahru, 81100

Malaysia

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Kuala Lumpur, 59100

Malaysia

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Kuala Selangor, 62250

Malaysia

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Malacca, 75000

Malaysia

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Bellavista, CALLAO 2

Peru

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Jesus Maria, Lima, LIMA 11

Peru

Research Site

Lima, 15036

Peru

Research Site

Lima, LIMA 29

Peru

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Biała Podlaska, 21-500

Poland

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Koszalin, 75-581

Poland

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Lodz, 93-338

Poland

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Lublin, 20-090

Poland

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Poznan, 60-569

Poland

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Poznan, 61-485

Poland

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Radom, 26-600

Poland

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Warsaw, 02-781

Poland

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Coimbra, 3000-075

Portugal

Research Site

Lisbon, 1099-023

Portugal

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Lisbon, 1998-018

Portugal

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Matosinhos Municipality, 4454-509

Portugal

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Porto, 4050-115

Portugal

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Vila Real, 5000-508

Portugal

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San Juan, 00918

Puerto Rico

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Daegu, 41404

South Korea

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Seongnam-si, 13620

South Korea

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Seoul, 02841

South Korea

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Seoul, 03080

South Korea

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Seoul, 06273

South Korea

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Seoul, 06351

South Korea

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Seoul, 3722

South Korea

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Seoul, 5505

South Korea

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A Coruña, 15009

Spain

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Barcelona, 08035

Spain

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Cáceres, 10003

Spain

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Granada, 18007

Spain

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L'Hospitalet de Llobregat, 08908

Spain

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Madrid, 28040

Spain

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Madrid, 28041

Spain

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Málaga, 29010

Spain

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Pamplona, 31008

Spain

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Seville, 41013

Spain

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Valencia, 46006

Spain

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Zaragoza, 50009

Spain

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New Taipei City, 23561

Taiwan

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Taichung,

Taiwan

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Tainan, 704

Taiwan

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Taipei, 100

Taiwan

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Taipei, 10449

Taiwan

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Taipei, 112

Taiwan

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Taoyuan, 00333

Taiwan

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Bangkok, 10210

Thailand

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Bangkok, 10330

Thailand

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Dusit, 10300

Thailand

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Hat Yai, 90110

Thailand

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Muang, 22000

Thailand

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Ratchathewi, 10400

Thailand

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Ratchathewi, 10400

Thailand

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Adapazarı, 54290

Turkey (Türkiye)

Research Site

Altındağ-Ankara, 06230

Turkey (Türkiye)

Research Site

Ankara, 06530

Turkey (Türkiye)

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Çankaya, 06680

Turkey (Türkiye)

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Istanbul, 34214

Turkey (Türkiye)

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Kayseri, 38039

Turkey (Türkiye)

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Cambridge, CB2 2QQ

United Kingdom

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Guildford, GU2 7XX

United Kingdom

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London, SE1 9RT

United Kingdom

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Manchester, M20 4BX

United Kingdom

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Oxford, OX3 7LE

United Kingdom

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Swansea, SA2 8QA

United Kingdom

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Taunton, TA1 5DA

United Kingdom

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Truro, TR1 3LJ

United Kingdom