Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT ID: NCT06350097

Last Updated: 2025-11-17

Study Results

Results pending

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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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

582 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-29

Study Completion Date

2032-05-25

Brief Summary

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The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Dato-DXd (i.v. infusion) compared with osimertinib (tablet) monotherapyas a first-line therapy in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC.

Study details include:

1. The study duration will be event-driven, with an estimated duration of approximately 9 years.
2. Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.
3. The visit frequency will be every 3 weeks during the treatment period.

Note: Participants on osimertinib treatment(osimertinib only arm or who have discontinued Dato-DXd while are still receiving osimertinib) are required to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and then visits every 12 weeks until disease progression or IP discontinuation. Participants who are receiving osimertinib + Dato-DXd are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA.

Detailed Description

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This is a global Phase III, open-label, randomised, multicentre study assessing the efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC who have not received any prior therapy for advanced disease.

Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Osimertinib in combination with Datopotamab Deruxtecan

Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.

Group Type EXPERIMENTAL

Osimertinib

Intervention Type DRUG

Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.

Arm 2: Osimertinib 80 mg QD as oral tablet .

Datopotamab Deruxtecan

Intervention Type DRUG

Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.

Arm 2: Osimertinib monotherapy

Participants in this group will receive osimertinib 80 mg QD as oral tablet.

Group Type ACTIVE_COMPARATOR

Osimertinib

Intervention Type DRUG

Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.

Arm 2: Osimertinib 80 mg QD as oral tablet .

Interventions

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Osimertinib

Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.

Arm 2: Osimertinib 80 mg QD as oral tablet .

Intervention Type DRUG

Datopotamab Deruxtecan

Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.

Intervention Type DRUG

Other Intervention Names

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Osimertinib: AZD9291 Datopotamab Deruxtecan: Dato-DXd, DS-1062a

Eligibility Criteria

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Inclusion Criteria

Age

1. Participant must be ≥ 18 years.

Type of Participant and Disease Characteristics
2. Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
3. Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
4. Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
5. The tumour harbors at least 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
6. For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
7. WHO performance status of 0 or 1.
8. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements.
9. Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention.

Sex and Contraceptive/Barrier Requirements
10. Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

11. All races, gender and ethnic groups are eligible for this study.

Exclusion Criteria

1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, psychiatric illness/social situations), history of allogenic organ transplant, and/or substance abuse which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
3. History of another primary malignancy.
4. Spinal cord compression and unstable brain metastases, as defined by Protocol.
5. Clinically significant corneal disease.
6. Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
7. Known HIV infection that is not well controlled, as defined by Protocol.
8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
9. Resting ECG with clinically abnormal findings, as defined by Protocol.
10. Uncontrolled or significant cardiac disease, as defined by Protocol.
11. Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
12. Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise.

Prior/Concomitant Therapy
13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy.

Prior/Concurrent Clinical Study Experience
14. Participants with a known history of severe hypersensitivity reactions to either Dato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs with a similar chemical structure or class to DXd and osimertinib.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Fountain Valley, California, United States

Site Status NOT_YET_RECRUITING

Research Site

Los Alamitos, California, United States

Site Status RECRUITING

Research Site

Los Angeles, California, United States

Site Status RECRUITING

Research Site

Los Angeles, California, United States

Site Status RECRUITING

Research Site

Orange, California, United States

Site Status WITHDRAWN

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San Diego, California, United States

Site Status RECRUITING

Research Site

Santa Monica, California, United States

Site Status RECRUITING

Research Site

Walnut Creek, California, United States

Site Status RECRUITING

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New Haven, Connecticut, United States

Site Status RECRUITING

Research Site

Washington D.C., District of Columbia, United States

Site Status WITHDRAWN

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Jacksonville, Florida, United States

Site Status RECRUITING

Research Site

Ocala, Florida, United States

Site Status RECRUITING

Research Site

Orange City, Florida, United States

Site Status RECRUITING

Research Site

Honolulu, Hawaii, United States

Site Status WITHDRAWN

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North Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

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Fort Wayne, Indiana, United States

Site Status RECRUITING

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Bethesda, Maryland, United States

Site Status RECRUITING

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Detroit, Michigan, United States

Site Status RECRUITING

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Saint Paul, Minnesota, United States

Site Status RECRUITING

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Bridgeton, Missouri, United States

Site Status WITHDRAWN

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St Louis, Missouri, United States

Site Status RECRUITING

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Las Vegas, Nevada, United States

Site Status RECRUITING

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Brooklyn, New York, United States

Site Status NOT_YET_RECRUITING

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New York, New York, United States

Site Status RECRUITING

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Dallas, Texas, United States

Site Status WITHDRAWN

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Houston, Texas, United States

Site Status RECRUITING

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Houston, Texas, United States

Site Status WITHDRAWN

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Webster, Texas, United States

Site Status RECRUITING

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Woodway, Texas, United States

Site Status RECRUITING

Research Site

Fairfax, Virginia, United States

Site Status RECRUITING

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Fort Belvoir, Virginia, United States

Site Status NOT_YET_RECRUITING

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Midlothian, Virginia, United States

Site Status RECRUITING

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Seattle, Washington, United States

Site Status WITHDRAWN

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Milwaukee, Wisconsin, United States

Site Status NOT_YET_RECRUITING

Research Site

Camperdown, , Australia

Site Status NOT_YET_RECRUITING

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Clayton, , Australia

Site Status RECRUITING

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Kogarah, , Australia

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South Brisbane, , Australia

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Westmead, , Australia

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Barretos, , Brazil

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Natal, , Brazil

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Porto Alegre, , Brazil

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Salvador, , Brazil

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São Paulo, , Brazil

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Edmonton, Alberta, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Beijing, , China

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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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Chengdu, , China

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Chongqing, , China

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Chongqing, , China

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Guangzhou, , China

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Hangzhou, , 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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Hefei, , China

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Jinan, , China

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Jinan, , China

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Kunming, , China

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Linhai, , China

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Ningbo, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Wenzhou, , 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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Yangzhou, , China

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Zhengzhou, , China

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Zhengzhou, , China

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Angers, , France

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Marseille, , France

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Paris, , France

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Strasbourg, , France

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Berlin, , Germany

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Cologne, , Germany

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Erfurt, , Germany

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Frankfurt, , Germany

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Göttingen, , Germany

Site Status NOT_YET_RECRUITING

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Immenhausen, , Germany

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Kiel, , Germany

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Mainz, , Germany

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München, , Germany

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Hong Kong, , Hong Kong

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Hong Kong, , Hong Kong

Site Status NOT_YET_RECRUITING

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Jordan, , Hong Kong

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Lai Chi Kok, , Hong Kong

Site Status NOT_YET_RECRUITING

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Bangalore, , India

Site Status RECRUITING

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Delhi, , India

Site Status SUSPENDED

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Hyderabad, , India

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Kolkata, , India

Site Status SUSPENDED

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Mysuru, , India

Site Status SUSPENDED

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Nagpur, , India

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Nashik, , India

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New Delhi, , India

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New Delhi, , India

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Vadodara, , India

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Varanasi, , India

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Milan, , Italy

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Monza, , Italy

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Orbassano, , Italy

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Padua, , Italy

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Parma, , Italy

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Chūōku, , Japan

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Fukuoka, , Japan

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Kashiwa, , Japan

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Kōtoku, , Japan

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Niigata, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Wakayama, , Japan

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Yokohama, , Japan

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Bystra, , Poland

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Olsztyn, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Rio Piedras, , Puerto Rico

Site Status RECRUITING

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San Juan, , Puerto Rico

Site Status NOT_YET_RECRUITING

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Erie, , South Korea

Site Status RECRUITING

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Goyang-si, , South Korea

Site Status RECRUITING

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Namdong-gu, , 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

Site Status RECRUITING

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Barcelona, , Spain

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Granada, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

Site Status RECRUITING

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Valencia, , Spain

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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 District, , Taiwan

Site Status RECRUITING

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Bangkok, , Thailand

Site Status RECRUITING

Research Site

Bangkok, , Thailand

Site Status RECRUITING

Research Site

Dusit, , Thailand

Site Status RECRUITING

Research Site

Hat Yai, , Thailand

Site Status RECRUITING

Research Site

Udon Thani, , Thailand

Site Status RECRUITING

Research Site

Adapazarı, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Goztepe Istanbul, , Turkey (Türkiye)

Site Status WITHDRAWN

Research Site

Izmir, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Research Site

Küçükçekmece, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Seyhan, , Turkey (Türkiye)

Site Status RECRUITING

Research Site

Hanoi, , Vietnam

Site Status RECRUITING

Research Site

Hà Nội, , Vietnam

Site Status RECRUITING

Research Site

Ho Chi Minh City, , Vietnam

Site Status RECRUITING

Research Site

Ho Chi Minh City, , Vietnam

Site Status RECRUITING

Research Site

Ho Chi Minh City, , Vietnam

Site Status RECRUITING

Research Site

Vinh, , Vietnam

Site Status RECRUITING

Countries

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United States Australia Brazil Canada China France Germany Hong Kong India Italy Japan Poland Puerto Rico South Korea Spain Taiwan Thailand Turkey (Türkiye) Vietnam

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

Other Identifiers

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2023-509883-89-00

Identifier Type: OTHER

Identifier Source: secondary_id

D516NC00001

Identifier Type: -

Identifier Source: org_study_id

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