Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations

NCT ID: NCT05687266

Last Updated: 2025-12-10

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-29

Study Completion Date

2027-11-01

Brief Summary

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This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).

Detailed Description

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Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment.

The primary objectives of the study are to demonstrate superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:

1. PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
2. OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
3. PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
4. OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC

Conditions

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NSCLC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

None (Open Label)

Study Groups

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Dato-DXd + Durvalumab + Carboplatin

Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve \[AUC\] 5 mg/mL/minute.

Group Type EXPERIMENTAL

Datopotamab deruxtecan

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Durvalumab

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Carboplatin

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Histologic-specific therapy

Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin.

Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.

Group Type ACTIVE_COMPARATOR

Carboplatin

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Pembrolizumab

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle for a maximum of 35 cycles or 2 years (whichever occurs first).

Cisplatin

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Pemetrexed

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

Paclitaxel

Intervention Type DRUG

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Interventions

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Datopotamab deruxtecan

Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Intervention Type DRUG

Durvalumab

Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Intervention Type DRUG

Carboplatin

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Intervention Type DRUG

Pembrolizumab

Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle for a maximum of 35 cycles or 2 years (whichever occurs first).

Intervention Type DRUG

Cisplatin

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Intervention Type DRUG

Pemetrexed

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

Intervention Type DRUG

Paclitaxel

Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Intervention Type DRUG

Other Intervention Names

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Dato-DXd, Datroway MEDI4736, Imfinzi

Eligibility Criteria

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Inclusion Criteria

* Participants ≥ 18 years at screening
* Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
* Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).

Testing is not required for tumors with squamous histology, with exceptions.

* ECOG PS of 0 or 1
* Archival tumour tissue
* Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion:

* Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
* History of another primary malignancy with exceptions
* Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
* Spinal cord compression or clinically or radiologically active brain metastases
* History of leptomeningeal carcinomatosis.
* Known active or uncontrolled hepatitis B or C virus infection.
* Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
* Clinically significant corneal disease
* History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charu Aggarwal

Role: STUDY_CHAIR

Perelman Center for Advanced Medicine

Locations

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Hot Springs, Arkansas, United States

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Little Rock, Arkansas, United States

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Springdale, Arkansas, United States

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Fountain Valley, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Boulder, Colorado, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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St. Petersburg, Florida, United States

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West Palm Beach, Florida, United States

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Hinsdale, Illinois, United States

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Fort Wayne, Indiana, United States

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Bettendorf, Iowa, United States

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Iowa City, Iowa, United States

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Waukee, Iowa, United States

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Baton Rouge, Louisiana, United States

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Covington, Louisiana, United States

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Duluth, Minnesota, United States

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Rochester, Minnesota, United States

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Hannibal, Missouri, United States

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Lincoln, Nebraska, United States

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Lincoln, Nebraska, United States

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Clifton Park, New York, United States

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Asheville, North Carolina, United States

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Canton, Ohio, United States

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Columbus, Ohio, United States

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Maumee, Ohio, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Salem, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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York, Pennsylvania, United States

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Watertown, South Dakota, United States

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Memphis, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Irving, Texas, United States

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Fairfax, Virginia, United States

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Henrico, Virginia, United States

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Norfolk, Virginia, United States

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Renton, Washington, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Appleton, Wisconsin, United States

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La Crosse, Wisconsin, United States

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Graz, , Austria

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Rankweil, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Blumenau, , Brazil

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Florianópolis, , Brazil

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Fortaleza, , Brazil

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Londrina, , Brazil

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Porto Alegre, , 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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São Paulo, , Brazil

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Taubaté, , Brazil

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Vitória, , Brazil

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Saint John, New Brunswick, Canada

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Brampton, Ontario, Canada

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Greater Sudbury, Ontario, Canada

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Kitchener, Ontario, Canada

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Newmarket, 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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Saint-Jérôme, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , 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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Guangzhou, , China

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Guangzhou, , China

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Hefei, , China

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Jinan, , China

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Kunming, , China

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Lanzhou, , China

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Liuchow, , China

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Shandong, , China

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Shanghai, , 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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Shenzhen, , China

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Taiyuan, , China

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Tianjin, , China

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Wenzhou, , China

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Wuhan, , China

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Wuhan, , China

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Xiamen, , China

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Yangzhou, , China

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Zhengzhou, , China

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Brest, , France

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Créteil, , France

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Gleizé, , France

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Montpellier, , France

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Nîmes, , France

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Paris, , France

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Paris, , France

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Rouen, , France

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Saint-Quentin, , France

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Strasbourg, , France

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Toulon, , France

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Toulouse, , France

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Tours, , France

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Bad Berka, , Germany

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Berlin, , Germany

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Frankfurt A. Main, , Germany

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Gauting, , Germany

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Gütersloh, , Germany

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Hamburg, , Germany

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Kassel, , Germany

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Kiel, , Germany

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Koblenz, , Germany

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Minden, , Germany

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Rosenheim, , Germany

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Velbert, , Germany

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Würzburg, , Germany

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Piraeus, , Greece

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Thessaloniki, , Greece

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Thessaloniki, , Greece

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Budapest, , Hungary

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Budapest, , Hungary

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Gyöngyös - Mátraháza, , Hungary

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Kaposvár, , Hungary

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Pécs, , Hungary

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Szekszárd, , Hungary

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Szolnok, , Hungary

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Törökbálint, , Hungary

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Calicut, , India

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Delhi, , India

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Delhi, , India

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Jaipur, , India

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Kolkata, , India

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Madurai, , India

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Puducherry, , India

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Florence, , Italy

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Lecco, , Italy

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Messina, , Italy

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Napoli, , Italy

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Orbassano, , Italy

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Padua, , Italy

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Parma, , Italy

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Peschiera del Garda, , Italy

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Rozzano, , Italy

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Bunkyō City, , Japan

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Chūōku, , Japan

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Hamamatsu, , Japan

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Hamamatsu, , Japan

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Hidaka-shi, , Japan

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Hirosaki-shi, , Japan

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Hiroshima, , Japan

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Kumamoto, , Japan

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Nagoya, , Japan

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Nagoya, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sapporo, , Japan

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Sunto-gun, , Japan

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Wakayama, , Japan

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Yokohama, , Japan

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Yokohama, , Japan

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Del. Cuauhtemoc, , Mexico

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Mexico City, , Mexico

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México, , Mexico

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San Luis Potosí City, , Mexico

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Arequipa, , Peru

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Concepción, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Bydgoszcz, , Poland

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Bystra, , Poland

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Grudziądz, , Poland

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Kielce, , Poland

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Koszalin, , Poland

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Olsztyn, , Poland

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Poznan, , Poland

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Przemyśl, , Poland

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Racibórz, , Poland

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Radom, , Poland

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Siedlce, , Poland

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Busan, , South Korea

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Cheongju-si, , South Korea

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Jinju, , 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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Seoul, , South Korea

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Suwon, , South Korea

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Suwon, , South Korea

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Las Palmas de Gran Canaria, , Spain

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Lugo, , Spain

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Madrid, , Spain

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Santander, , Spain

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Seville, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Gävle, , Sweden

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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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Hsinchu, , 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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Taoyuan District, , Taiwan

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Aberdeen, , United Kingdom

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Cambridge, , United Kingdom

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Cardiff, , United Kingdom

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Cheltenham, , United Kingdom

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Edinburgh, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Middlesbrough, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Taunton, , United Kingdom

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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United States Austria Brazil Bulgaria Canada China France Germany Greece Hungary India Italy Japan Mexico Peru Poland South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom Vietnam

Other Identifiers

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2021-004606-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D926NC00001

Identifier Type: -

Identifier Source: org_study_id

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