Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment

NCT ID: NCT05261399

Last Updated: 2025-01-10

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

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

324 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-03

Study Completion Date

2026-12-17

Brief Summary

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Clinical study to investigate the efficacy and safety of savolitinib in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on treatment with Osimertinib.

Detailed Description

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This is a multicentre, Phase III, randomised, open-label study to investigate the efficacy and safety of savolitinib administered orally in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with osimertinib as the most recent therapy.

Approximately 324 participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC will be randomly assigned to study intervention with 1:1 ratio.

Patients will be treated until either objective progression of disease (PD) by Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

Conditions

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Carcinoma Non-Small-Cell Lung

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel Assignment
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemotherapy

Pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21-day cycles (Q3W) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W

Group Type ACTIVE_COMPARATOR

Pemetrexed

Intervention Type DRUG

Pemetrexed (500 mg/m2) Administrative route : IV infusion

Cisplatin

Intervention Type DRUG

Cisplatin (75 mg/m2) or Administrative route : IV infusion

Carboplatin

Intervention Type DRUG

Carboplatin (AUC5) Administrative route : IV infusion

Savolitinib + Osimertinib

300 mg savolitinib BID plus 80 mg osimertinib QD

Group Type EXPERIMENTAL

Savolitinib

Intervention Type DRUG

300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral

Osimertinib

Intervention Type DRUG

80 mg osimertinib

(1 × 80 mg tablet once daily) Administrative route : oral

Interventions

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Savolitinib

300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral

Intervention Type DRUG

Osimertinib

80 mg osimertinib

(1 × 80 mg tablet once daily) Administrative route : oral

Intervention Type DRUG

Pemetrexed

Pemetrexed (500 mg/m2) Administrative route : IV infusion

Intervention Type DRUG

Cisplatin

Cisplatin (75 mg/m2) or Administrative route : IV infusion

Intervention Type DRUG

Carboplatin

Carboplatin (AUC5) Administrative route : IV infusion

Intervention Type DRUG

Other Intervention Names

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AZD6094, HMPL-504, volitinib AZD9291, Tagrisso NAP NAP NAP

Eligibility Criteria

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Inclusion Criteria

* Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses.
* Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of signing the informed consent. All genders are permitted.
* Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy.
* Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R mutation, and/or T790M.
* Documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy.
* Mandatory provision of FFPE tumour tissue.
* MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment.
* Measurable disease as defined by RECIST 1.1.
* Adequate haematological, liver, renal and cardiac functions, and coagulation parameters.
* ECOG performance status of 0 or 1.

Exclusion Criteria

* Predominant squamous NSCLC, and small cell lung cancer.
* Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib.
* Prior or current treatment with savolitinib or another MET inhibitors.
* Spinal cord compression or brain metastases, unless asymptomatic and are stable.
* History or active leptomeningeal carcinomatosis.
* Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 and prior platinum-therapy related Grade 2 neuropathies with the exception of alopecia and haemoglobin ≥ 9.0 g/dL.
* Active/unstable cardiac diseases currently or within the last 6 months, clinically significant ECG abnormalities, and/or factors/medications that may affect QTc intervals.
* History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement.
* Known serious active infection including, but not limited to, tuberculosis, or HIV, HBV or HCV or gastrointestinal disease.
* Receipt of live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of study intervention.
* Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required steroid treatment, or any evidence of clinically active ILD.
* Participants currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2.
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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Shun Lu, Prof,MD,PhD,

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.

Locations

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Research Site

La Jolla, California, United States

Site Status WITHDRAWN

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Orange City, Florida, United States

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Orlando, Florida, United States

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Honolulu, Hawaii, United States

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Evergreen Park, Illinois, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Florham Park, New Jersey, United States

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New Brunswick, New Jersey, United States

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New York, New York, United States

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Canton, Ohio, United States

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Nashville, Tennessee, United States

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Berazategui, , Argentina

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Buenos Aires, , Argentina

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CABA, , Argentina

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Córdoba, , Argentina

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Florida, , Argentina

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La Rioja, , Argentina

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Rosario, , Argentina

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Rosario, , Argentina

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San Miguel de Tucumán, , Argentina

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Viedma, , Argentina

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Clayton, , Australia

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Fremantle, , Australia

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Geelong, , Australia

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Liverpool, , Australia

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Southport, , Australia

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Waratah NSW, , Australia

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Westmead, , Australia

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Graz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Brussels, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Hasselt, , Belgium

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Mons, , Belgium

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Roeselare, , Belgium

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Sint-Niklaas, , Belgium

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Belo Horizonte, , Brazil

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Brasília, , Brazil

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Cachoeiro de Itapemirim, , Brazil

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Curitiba, , Brazil

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Ijuí, , Brazil

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Ipatinga, , Brazil

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Porto Alegre, , 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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Rio de Janeiro, , Brazil

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Salvador, , 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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Vitória, , Brazil

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Haskovo, , Bulgaria

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Vratsa, , Bulgaria

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Calgary, Alberta, Canada

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Mississauga, 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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Santiago, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Baoding, , China

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Beijing, , China

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Beijing, , China

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Bengbu, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Changsha, , 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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Hangzhou, , China

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Hankou,Wuhan, , China

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Harbin, , China

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Hefei, , China

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Jinan, , China

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Linyi, , China

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Nanchang, , China

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Qingdao, , China

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Shanghai, , China

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Shenyang, , China

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Shenzhen, , 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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Xiangyang, , China

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Yichang, , China

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Zhengzhou, , China

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Angers, , France

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Bobigny, , France

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Bordeaux, , France

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Brest, , France

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Créteil, , France

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Dijon, , France

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Marseille, , France

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Montpellier, , France

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Paris, , France

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Paris, , France

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Poitiers, , France

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Rennes, , France

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Rouen, , France

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Saint-Herblain, , France

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Saint-Quentin, , France

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Strasbourg, , France

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Suresnes, , France

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Berlin, , Germany

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Berlin, , Germany

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Chemnitz, , Germany

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Frankfurt A. Main, , Germany

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Gauting, , Germany

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Homburg, , Germany

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Immenhausen, , Germany

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Löwenstein, , Germany

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München, , Germany

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Münster, , Germany

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Stuttgart, , Germany

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Wangen, , Germany

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Athens, , Greece

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Athens, , Greece

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Chaïdári, , Greece

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Heraklion, , Greece

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Larissa, , Greece

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Rio, , Greece

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Thessaloniki, , Greece

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Thessaloniki, , Greece

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Hong Kong, , Hong Kong

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Kowloon, , Hong Kong

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Afula, , Israel

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Ashdod, , Israel

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Be’er Ya‘aqov, , Israel

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Hadera, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Avellino, , Italy

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Aviano, , Italy

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Catania, , Italy

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Meldola, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Monserrato, , 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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Perugia, , Italy

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Peschiera del Garda, , Italy

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Roma, , Italy

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Roma, , Italy

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Treviso, , Italy

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Bunkyō City, , Japan

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Chūōku, , Japan

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Fukuoka, , Japan

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Hirosaki-shi, , Japan

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Hiroshima, , Japan

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Iwakuni-shi, , Japan

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Kanazawa, , Japan

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Kashiwa, , Japan

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Kobe, , Japan

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Kobe, , Japan

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Kumamoto, , Japan

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Kurume-shi, , Japan

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Matsuyama, , Japan

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Nagasaki, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sakaishi, , Japan

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Sapporo, , Japan

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Sapporo, , Japan

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Sendai, , Japan

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Sunto-gun, , Japan

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Utsunomiya, , Japan

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Wakayama, , Japan

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Yokohama, , Japan

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Kota Bharu, , Malaysia

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Kuala Lumpur, , Malaysia

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Petaling Jaya, , Malaysia

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Pulau Pinang, , Malaysia

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Sabak Bernam, , Malaysia

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Amsterdam, , Netherlands

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Bacolod, , Philippines

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Baguio City, , Philippines

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Cebu, , Philippines

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Cebu City, , Philippines

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Davao City, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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San Juan City, , Philippines

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Bialystok, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Olsztyn, , Poland

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Chelyabinsk, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Tomsk, , Russia

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Singapore, , Singapore

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Singapore, , Singapore

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Goyang-si, , South Korea

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Gyeonggi-do, , South Korea

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Incheon, , 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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Ulsan, , South Korea

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A Coruña, , Spain

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Badajoz, , Spain

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Badalona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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Girona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Pontevedra, , Spain

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Sabadell, , Spain

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Seville, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Baden, , Switzerland

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Basel, , Switzerland

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Bern, , Switzerland

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Winterthur, , Switzerland

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Zurich, , Switzerland

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Chiayi City, , Taiwan

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Hsinchu, , Taiwan

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Kaohsiung City, , Taiwan

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Liuying, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chanthaburi, , Thailand

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Chiang Mai, , Thailand

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Dusit, , Thailand

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Hat Yai, , Thailand

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Muang, , Thailand

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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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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Bristol, , United Kingdom

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Leicester, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Newport, , United Kingdom

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Reading, , United Kingdom

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Wolverhampton, , United Kingdom

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Can Tho, , Vietnam

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Hanoi, , Vietnam

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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United States Argentina Australia Austria Belgium Brazil Bulgaria Canada Chile China France Germany Greece Hong Kong Israel Italy Japan Malaysia Netherlands Philippines Poland Russia Singapore South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

AstraZeneca Lung Cancer Study Locator Service

Role: CONTACT

1-884-432-3892

Related Links

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https://www.lungcancerstudylocator.com/trial/listing/335213

Lung Cancer Study Locator details (for US)

Other Identifiers

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2024-511169-12-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-006374-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5087C00001

Identifier Type: -

Identifier Source: org_study_id

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