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Saruparib (AZD5305) Plus Camizestrant 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

NCT06380751 · AstraZeneca
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Official title
A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)
About this study
Approximately 2,620 participants will be screened to achieve approximately 500 participants randomised to study intervention. Participants will be randomised in a 2:2:1 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 Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.
Eligibility criteria
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 up to 28 days 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.
Study design
Enrollment target: 500 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-08-01
Estimated completion: 2030-10-18
Last updated: 2026-05-15
Interventions
Drug: Saruparib (AZD5305)Drug: CamizestrantDrug: AbemaciclibDrug: RibociclibDrug: PalbociclibDrug: FulvestrantDrug: LetrozoleDrug: AnastrozoleDrug: Exemestane
Primary outcomes
  • Progression-Free Survival (Up to approximately 59 months)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
All locations (298)
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Gilbert, Arizona, United States
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Fountain Valley, California, United States
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Glendale, California, United States
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Los Angeles, California, United States
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Newport Beach, California, United States
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Aurora, Colorado, United States
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Grand Junction, Colorado, United States
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Hollywood, Florida, United States
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Jacksonville, Florida, United States
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Orlando, Florida, United States
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Chicago, Illinois, United States
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Evanston, Illinois, United States
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Park Ridge, Illinois, United States
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Urbana, Illinois, United States
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Winfield, Illinois, United States
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Indianapolis, Indiana, United States
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Louisville, Kentucky, United States
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Baltimore, Maryland, United States
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Silver Spring, Maryland, United States
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Silver Spring, Maryland, United States
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Boston, Massachusetts, United States
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Dearborn, Michigan, United States
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Detroit, Michigan, United States
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Royal Oak, Michigan, United States
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Royal Oak, Michigan, United States
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Rochester, Minnesota, United States
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Springfield, Missouri, United States
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St Louis, Missouri, United States
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Camden, New Jersey, United States
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New Brunswick, New Jersey, United States
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Brooklyn, New York, United States
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Mineola, New York, United States
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New Hyde Park, New York, United States
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New York, New York, United States
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New York, New York, United States
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New York, New York, United States
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Shirley, New York, United States
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Stony Brook, New York, United States
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The Bronx, New York, United States
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Westbury, New York, United States
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Hershey, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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West Columbia, South Carolina, United States
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Chattanooga, Tennessee, United States
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Nashville, Tennessee, United States
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Houston, Texas, United States
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Houston, Texas, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Norfolk, Virginia, United States
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Tacoma, Washington, United States
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Morgantown, West Virginia, United States
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Milwaukee, Wisconsin, United States
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Ciudad Autónoma Buenos Aires, Argentina
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Ciudad de Buenos Aires, Argentina
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Ciudad de Buenos Aires, Argentina
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Córdoba, Argentina
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Rosario, Argentina
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Salta, Argentina
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San Miguel de Tucumán, Argentina
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Darlinghurst, Australia
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Darlinghurst, Australia
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Malvern, Australia
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Melbourne, Australia
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Graz, Austria
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Innsbruck, Austria
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Linz, Austria
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Vienna, Austria
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Cachoeira de Itapemirim, Brazil
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Curitiba, Brazil
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Fortaleza, Brazil
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Goiânia, Brazil
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Jaú, Brazil
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Porto Alegre, Brazil
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Ribeirão Preto, Brazil
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Salvador, Brazil
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São Paulo, Brazil
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Plovdiv, Bulgaria
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Sofia, Bulgaria
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Stara Zagora, Bulgaria
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Vratsa, Bulgaria
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Toronto, Ontario, Canada
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Greenfield Park, Quebec, Canada
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Montreal, Quebec, Canada
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Montreal, Quebec, Canada
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Saskatoon, Saskatchewan, Canada
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Toronto, Canada
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Providencia, Chile
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Recoleta, Chile
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Santiago, Chile
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Talca, Chile
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Viña del Mar, Chile
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Beijing, China
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Bengbu, China
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Changchun, China
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Changchun, China
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Changsha, China
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Changsha, China
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Chengdu, China
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Chengdu, China
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Chongqing, China
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Foshan, China
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Fuzhou, China
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Guangzhou, China
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Guangzhou, China
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Guangzhou, China
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Hangzhou, China
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Hangzhou, China
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Harbin, China
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Hefei, China
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Hohhot, China
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Jining, China
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Kunming, China
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Liuzhou, China
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Luoyang, China
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Nanchang, China
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Nanchang, China
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Nanjing, China
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Shandong, China
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Shanghai, China
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Shanghai, China
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Shenyang, China
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Shijiazhuang, China
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Tianjin, China
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Weifang, China
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Wuhan, China
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Wuhan, China
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Wuhan, China
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Xi'an, China
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Xi'an, China
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Xiamen, China
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Xiangyang, China
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Xinxiang, China
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Zhengzhou, China
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Brno, Czechia
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Hořovice, Czechia
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Hradec Králové, Czechia
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Prague, Czechia
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Prague, Czechia
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Angers, France
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Besançon, France
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Lille, France
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Lyon, France
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Marseille, France
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Paris, France
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Rouen, France
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Saint-Herblain, France
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Toulouse, France
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Aachen, Germany
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Augsburg, Germany
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Berlin, Germany
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Düsseldorf, Germany
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Erlangen, Germany
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Heidelberg, Germany
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Kiel, Germany
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Leipzig, Germany
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München, Germany
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Budapest, Hungary
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Budapest, Hungary
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Debrecen, Hungary
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Miskolc, Hungary
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Zalaegerszeg, Hungary
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Delhi, India
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Kolkata, India
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Lucknow, India
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Mumbai, India
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Mumbai, India
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Mysuru, India
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Nagpur, India
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Nashik, India
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New Delhi, India
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Surat, India
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Thiruvananthapuram, India
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Jerusalem, Israel
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Jerusalem, Israel
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Petah Tikva, Israel
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Ramat Gan, Israel
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Tel Aviv, Israel
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Bergamo, Italy
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Bologna, Italy
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Milan, Italy
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Milan, Italy
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Modena, Italy
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Naples, Italy
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Reggio Emilia, Italy
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Rome, Italy
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Rozzano, Italy
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Chiba, Japan
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Kagoshima, Japan
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Kashiwa, Japan
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Kōtoku, Japan
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Kyoto, Japan
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Nagoya, Japan
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Osaka, Japan
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Sapporo, Japan
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Sendai, Japan
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Shinagawa-ku, Japan
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Suita-shi, Japan
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Sunto-gun, Japan
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Takasaki-shi, Japan
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Tsu, Japan
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Yokohama, Japan
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Bandar Puncak Alam, Malaysia
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Johor Bahru, Malaysia
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Kuala Lumpur, Malaysia
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Kuala Selangor, Malaysia
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Malacca, Malaysia
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Bellavista, Peru
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Lima, Peru
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Lima, Peru
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Lodz, Poland
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Poznan, Poland
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Radom, Poland
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Warsaw, Poland
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Coimbra, Portugal
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Lisbon, Portugal
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Lisbon, Portugal
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Matosinhos Municipality, Portugal
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Porto, Portugal
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Vila Real, Portugal
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San Juan, Puerto Rico
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Daegu, South Korea
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Seongnam-si, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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A Coruña, Spain
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Barcelona, Spain
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Cáceres, Spain
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Granada, Spain
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L'Hospitalet de Llobregat, Spain
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Madrid, Spain
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Madrid, Spain
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Málaga, Spain
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Pamplona, Spain
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Seville, Spain
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New Taipei City, Taiwan
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Taichung, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Taipei, Taiwan
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Taipei, Taiwan
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Taoyuan, Taiwan
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Bangkok, Thailand
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Bangkok, Thailand
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Dusit, Thailand
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Hat Yai, Thailand
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Muang, Thailand
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Ratchathewi, Thailand
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Ratchathewi, Thailand
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Adapazarı, Turkey (Türkiye)
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Altındağ-Ankara, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Çankaya, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Kayseri, Turkey (Türkiye)
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Cambridge, United Kingdom
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Guildford, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Oxford, United Kingdom
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Swansea, United Kingdom
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Taunton, United Kingdom
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Truro, United Kingdom
Saruparib (AZD5305) Plus Camizestrant 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 · TrialPath