DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer
NCT ID: NCT06989112
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
600 participants
INTERVENTIONAL
2025-03-27
2031-02-19
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: T-DXd + Rilvegostomig
T-DXd IV Q3W plus rilvegostomig IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first.
Trastuzumab deruxtecan
Experimental therapy by intravenous infusion
Rilvegostomig
Experimental therapy by intravenous infusion
Arm B: T-DXd + Pembrolizumab
T-DXd IV Q3W plus pembrolizumab IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first.
Trastuzumab deruxtecan
Experimental therapy by intravenous infusion
Pembrolizumab
Immunotherapy by intravenous infusion
Arm C: Carboplatin + Paclitaxel + Pembrolizumab
Carboplatin, paclitaxel and pembrolizumab administered Q3W during 6 cycles, followed by maintenance with pembrolizumab IV Q6W during 14 cycles. Treatment with pembrolizumab will continue for up to 20 total cycles (approximately 24 months, accounting for combination and maintenance phases) or until other discontinuation criteria is met, whichever occurs first. At the discretion of the investigator, participants may continue to receive carboplatin, paclitaxel and pembrolizumab Q3W for up to 10 cycles. Docetaxel can be used as an alternative to paclitaxel for participants who had a hypersensitivity reaction to paclitaxel with a failed rechallenge (or not amenable to rechallenge), according to the investigator's clinical judgment.
Pembrolizumab
Immunotherapy by intravenous infusion
Carboplatin
Standard of Care (SoC) chemotherapy by intravenous infusion
Paclitaxel
Standard of Care (SoC) chemotherapy by intravenous infusion
Docetaxel
Standard of Care (SoC) chemotherapy by intravenous infusion
Interventions
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Trastuzumab deruxtecan
Experimental therapy by intravenous infusion
Rilvegostomig
Experimental therapy by intravenous infusion
Pembrolizumab
Immunotherapy by intravenous infusion
Carboplatin
Standard of Care (SoC) chemotherapy by intravenous infusion
Paclitaxel
Standard of Care (SoC) chemotherapy by intravenous infusion
Docetaxel
Standard of Care (SoC) chemotherapy by intravenous infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies are allowed except for sarcomas (carcinosarcomas are allowed).
* Following surgery or diagnostic biopsy, participant must have primary advanced disease (Stage III/IV) or first recurrent endometrial cancer and meet at least one of the following criteria:
* Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator's assessment.
* Primary Stage IV disease (per FIGO 2023) regardless of presence of measurable disease at baseline.
* First recurrent disease regardless of presence of measurable disease at baseline.
* Endometrial cancer with HER2 IHC expression of 3+ or 2+ as assessed by prospective central testing.
* Endometrial cancer that is determined pMMR by prospective central IHC testing.
* Provision of adequate FFPE tumor tissue sample of a tumor lesion that was not previously irradiated for central HER2, MMR, and PD-L1 IHC testing and valid central test results for randomization/ stratification.
* Prior therapy:
* Naïve to first-line systemic anticancer therapy. Participants may have received one prior line of adjuvant/neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if disease recurrence or progression occurred ≥ 6 months after last dose of chemotherapy. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed.
* No prior exposure to ADCs or immune checkpoint inhibitors including (but not limited to) anti-PD-1/PD-L1/PD-L2 and anti-CTLA-4 antibodies and therapeutic anticancer vaccines.
* Participants may have received prior radiation therapy for the treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Adequate treatment washout period is required.
* Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
* Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.
* Adequate organ and bone marrow function within 14 days before randomization.
Exclusion Criteria
* Uncontrolled intercurrent illness, including, but not limited to ongoing or active known infection, serious chronic gastrointestinal conditions associated with diarrhea and active non-infectious skin disease requiring systemic treatment.
* Spinal cord compression or clinically active central nervous system metastases
* Participants with a medical history of myocardial infarction (MI) within 6 months before randomization, or symptomatic congestive heart failure (CHF) (NYHA Class II to IV), clinically significant arrhythmia, or cardiomyopathy of any etiology. Participants with troponin levels above ULN at screening (as defined by the manufacturer), should have a cardiologic consultation before enrollment to rule out MI
* History of (non-infectious) ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* Lung criteria:
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.).
* Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of screening.
* Prior pneumonectomy (complete).
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* Active primary immunodeficiency/ active infectious disease(s) including:
* Tuberculosis (TB)
* HIV infection that is not well controlled.
* Chronic or active hepatitis B, chronic or active hepatitis C; however, participants who have chronic hepatitis B and are receiving suppressive antiviral therapy are allowed to be enrolled if alanine aminotransferase (ALT) is normal and viral load is controlled.
* Any concurrent anticancer treatment without an adequate washout period prior to the first dose of study intervention. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., HRT) is allowed.
18 Years
FEMALE
No
Sponsors
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Daiichi Sankyo Co., Ltd.
INDUSTRY
Gynecologic Oncology Group (GOG) Foundation Inc.
UNKNOWN
European Network for Gynaecological Oncological Trial groups(ENGOT)
UNKNOWN
AstraZeneca
INDUSTRY
Responsible Party
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Locations
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Tucson, Arizona, United States
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Little Rock, Arkansas, United States
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Duarte, California, United States
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La Jolla, California, United States
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Palo Alto, California, United States
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San Francisco, California, United States
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Sylmar, California, United States
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Fort Myers, Florida, United States
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Miami Beach, Florida, United States
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St. Petersburg, Florida, United States
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Tampa, Florida, United States
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West Palm Beach, Florida, United States
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Augusta, Georgia, United States
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Honolulu, Hawaii, United States
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Arlington Heights, Illinois, United States
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Evanston, Illinois, United States
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Shreveport, Louisiana, United States
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Baltimore, Maryland, United States
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Boston, Massachusetts, United States
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Worcester, Massachusetts, United States
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Ann Arbor, Michigan, United States
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Detroit, Michigan, United States
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Minneapolis, Minnesota, United States
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Rochester, Minnesota, United States
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Jackson, Mississippi, United States
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Springfield, Missouri, United States
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St Louis, Missouri, United States
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Las Vegas, Nevada, United States
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Hackensack, New Jersey, United States
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Albuquerque, New Mexico, 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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Charlotte, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Cincinnati, Ohio, United States
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Columbus, Ohio, United States
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Tulsa, Oklahoma, United States
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Eugene, Oregon, United States
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Abington, Pennsylvania, 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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Providence, Rhode Island, United States
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Charleston, South Carolina, United States
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Sioux Falls, South Dakota, United States
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Austin, Texas, United States
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Fort Worth, Texas, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Saint Johnsbury, Vermont, United States
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Charlottesville, Virginia, United States
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Fairfax, Virginia, United States
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Seattle, Washington, United States
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Madison, Wisconsin, United States
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Blacktown, , Australia
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East Melbourne, , Australia
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Nedlands, , Australia
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South Brisbane, , Australia
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Innsbruck, , Austria
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Linz, , Austria
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Vienna, , Austria
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Wein, , Austria
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Anderlecht, , Belgium
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Brussels, , Belgium
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Charleroi, , Belgium
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Ghent, , Belgium
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Leuven, , Belgium
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Liège, , Belgium
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Barretos, , Brazil
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Belo Horizonte, , Brazil
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Goiânia, , Brazil
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Londrina, , Brazil
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Porto Alegre, , Brazil
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Porto Alegre, , Brazil
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Rio de Janeiro, , Brazil
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Salvador, , Brazil
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São Paulo, , Brazil
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São Paulo, , Brazil
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São Paulo, , Brazil
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Teresina, , Brazil
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
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Winnipeg, Manitoba, Canada
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Halifax, Nova Scotia, Canada
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Montreal, Quebec, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Beijing, , China
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Changchun, , 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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Fuzhou, , 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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Haikou, , China
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Hangzhou, , China
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Harbin, , China
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Hefei, , China
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Jinan, , China
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Jinan, , China
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Jining, , China
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Kunming, , China
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Lanzhou, , China
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Nanchang, , China
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Nanning, , China
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Shanghai, , China
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Shanghai, , China
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Shantou, , China
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Shenyang, , China
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Shenyang, , China
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Taiyuan, , China
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Tianjin, , China
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Ürümqi, , China
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Wuhan, , China
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Wuhan, , China
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Xi'an, , China
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Xuzhou, , China
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Yibin, , China
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Aalborg, , Denmark
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Herlev, , Denmark
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København Ø, , Denmark
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Odense, , Denmark
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Helsinki, , Finland
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Oulu, , Finland
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Tampere, , Finland
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Turku, , Finland
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Besançon, , France
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Bordeaux, , France
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Caen, , France
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Clermont-Ferrand, , France
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Lyon, , France
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Montpellier, , France
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Nice, , France
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Paris, , France
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Plérin, , France
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Poitiers, , France
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Saint-Herblain, , France
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Toulouse, , France
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Berlin, , Germany
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Chemnitz, , Germany
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Dessau, , Germany
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Dresden, , Germany
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Essen, , Germany
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Hamburg, , Germany
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Kassel, , Germany
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Leipzig, , Germany
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Mannheim, , Germany
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Marburg, , Germany
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Münster, , Germany
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Saarbrücken, , Germany
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Budapest, , Hungary
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Budapest, , Hungary
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Debrecen, , Hungary
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Catania, , Italy
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Florence, , Italy
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Milan, , Italy
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Milan, , Italy
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Milan, , Italy
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Monza, , Italy
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Napoli, , Italy
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Reggio Emilia, , Italy
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Roma, , Italy
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Rome, , Italy
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Torino, , Italy
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Turin, , Italy
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Akashi-shi, , Japan
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Ginowan-shi, , Japan
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Hidaka-shi, , Japan
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Isehara-shi, , Japan
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Kashiwa, , Japan
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Kashiwa-shi, , Japan
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Kobe, , Japan
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Kōtoku, , Japan
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Kurume-shi, , Japan
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Matsuyama, , Japan
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Morioka, , Japan
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Nagoya, , Japan
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Niigata, , Japan
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Osaka, , Japan
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Ota-shi, , Japan
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Sapporo, , Japan
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Sendai, , Japan
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Shinjuku-ku, , Japan
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Sunto-gun, , Japan
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Tokyo, , Japan
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Amsterdam, , Netherlands
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Leiden, , Netherlands
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Nijmegen, , Netherlands
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Rotterdam, , Netherlands
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Oslo, , Norway
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Stavanger, , Norway
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Bialystok, , Poland
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Gdansk, , Poland
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Lodz, , Poland
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Poznan, , Poland
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Siedlce, , Poland
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Szczecin, , Poland
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Goyang-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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Seoul, , South Korea
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Suwon, , South Korea
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A Coruña, , Spain
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Córdoba, , Spain
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Donostia / San Sebastian, , Spain
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El Palmar, , 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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Palma de Mallorca, , Spain
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Valencia, , Spain
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Valencia, , Spain
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Zaragoza, , Spain
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Linköping, , Sweden
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Lund, , Sweden
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Stockholm, , Sweden
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Uppsala, , Sweden
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Frauenfeld, , Switzerland
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Liestal, , Switzerland
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Sankt Gallen, , Switzerland
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Zurich, , Switzerland
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Changhua, , Taiwan
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Kaohsiung City, , Taiwan
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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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Bath, , United Kingdom
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Cambridge, , United Kingdom
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Leeds, , United Kingdom
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London, , United Kingdom
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Manchester, , United Kingdom
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Northwood, , United Kingdom
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Taunton, , United Kingdom
Countries
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Central Contacts
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AstraZeneca Clinical Study Information Center
Role: CONTACT
Phone: 1-877-240-9479
Email: [email protected]
Other Identifiers
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2023-508056-19-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
GOG-3098
Identifier Type: OTHER
Identifier Source: secondary_id
ENGOT-EN24
Identifier Type: OTHER
Identifier Source: secondary_id
D781DC00001
Identifier Type: -
Identifier Source: org_study_id