A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer

NCT ID: NCT04351555

Last Updated: 2025-05-23

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

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-16

Study Completion Date

2029-06-13

Brief Summary

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This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer

Detailed Description

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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

DOUBLE

Participants Investigators
The two arms with SoC chemotherapy (placebo plus chemotherapy versus osimertinib plus chemotherapy) will be double-blinded and placebo-controlled.

Osimertinib monotherapy arm will be open label, sponsor-blind.

Study Groups

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Arm 1: Placebo with platinum-based chemotherapy

Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)

Group Type PLACEBO_COMPARATOR

Cisplatin

Intervention Type DRUG

Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.

Carboplatin

Intervention Type DRUG

Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles

Placebo

Intervention Type DRUG

Oral

Pemetrexed

Intervention Type DRUG

Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles

Arm 2: Osimertinib with platinum-based chemotherapy

Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)

Group Type EXPERIMENTAL

Osimertinib

Intervention Type DRUG

Oral

Cisplatin

Intervention Type DRUG

Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.

Carboplatin

Intervention Type DRUG

Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles

Pemetrexed

Intervention Type DRUG

Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles

Arm 3: Osimertinib monotherapy

Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)

Group Type EXPERIMENTAL

Osimertinib

Intervention Type DRUG

Oral

Interventions

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Osimertinib

Oral

Intervention Type DRUG

Cisplatin

Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.

Intervention Type DRUG

Carboplatin

Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles

Intervention Type DRUG

Placebo

Oral

Intervention Type DRUG

Pemetrexed

Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles

Intervention Type DRUG

Other Intervention Names

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AZD9291; TAGRISSO

Eligibility Criteria

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Inclusion Criteria

* Male or female, at least 18 years of age. For patients aged \<20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative
* Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual \[IASLC Staging Manual in Thoracic Oncology 2016\]).
* Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).
* Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing
* A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (eg., T790M, G719X, Exon20 insertions, S7681 and L861Q).

Exclusion Criteria

* Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
* History of another primary malignancy (including any known or suspected synchronous primary lung cancer), except for the following: Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of investigational product (IP) and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease; Adequately treated carcinoma in situ without evidence of disease; Any synchronous Stage IA primary lung cancer that is ≤2 cm and planned to be resected during surgery for the Stage II to IIIB N2 lung tumour.
* Patients who have pre-operative radiotherapy treatment as part of their care plan
* Mixed small cell and NSCLC histology
* Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC
* T4 tumours infiltrating the great vessels, the carina, the trachea, the oesophagus, the heart, and/or the vertebral body; and/or any bulky N2 disease.
* Patients who are candidates to undergo only segmentectomies or wedge resections
* Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug
* Prior treatment with EGFR-TKI therapy
* Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 weeks prior)
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 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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Jamie Chaft, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering, USA

Masahiro Tsuboi, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center Hospital East, Japan

Walter Weder, MD

Role: PRINCIPAL_INVESTIGATOR

Thoraxchirurgie Bethanien, Switzerland

Locations

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Duarte, California, United States

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Irvine, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Santa Rosa, California, United States

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Boston, Massachusetts, United States

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Lebanon, New Hampshire, United States

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Commack, New York, United States

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New York, New York, United States

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Houston, Texas, United States

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Fairfax, Virginia, United States

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Seattle, Washington, United States

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Graz, , Austria

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Vienna, , Austria

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Barretos, , Brazil

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Fortaleza, , Brazil

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Jaú, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Recife, , Brazil

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Rio de Janeiro, , Brazil

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Santa Maria, , Brazil

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São José do Rio Preto, , 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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Panagyurishte, , Bulgaria

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Pleven, , Bulgaria

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Sofia, , Bulgaria

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Las Condes, , Chile

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Santiago, , Chile

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Santiago, , Chile

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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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Chongqing, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Kunming, , China

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Nanchang, , China

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Nantong, , 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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Suzhou, , China

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Ürümqi, , China

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Wanzhou, , China

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Wenzhou, , China

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Xiamen, , China

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Yangzhou, , China

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Avignon, , France

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Bordeaux, , France

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Berlin, , Germany

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Bielefeld, , Germany

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Cologne, , Germany

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Esslingen a.N., , Germany

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Freiburg im Breisgau, , Germany

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Gauting, , Germany

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Georgsmarienhütte, , Germany

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Halle, , Germany

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Oldenburg, , Germany

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Würzburg, , Germany

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Mumbai, , India

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Namakkal, , India

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New Delhi, , India

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Varanasi, , India

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Haifa, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Bari, , Italy

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Florence, , Italy

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Monza, , Italy

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Orbassano, , Italy

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Padua, , Italy

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Rozzano, , Italy

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Varese, , Italy

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Akashi-shi, , Japan

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Bunkyō City, , Japan

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Chiba, , Japan

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Hiroshima, , Japan

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Kashiwa, , Japan

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Kōtoku, , Japan

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Kyoto, , Japan

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Niigata, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sakaishi, , 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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Yokohama, , Japan

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Aguascalientes, , Mexico

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D.F, , Mexico

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Mexico City, , Mexico

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La Libertad, , 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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Olsztyn, , Poland

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Kazan', , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Obninsk, , Russia

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Perm, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Daegu, , South Korea

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Hwasun-gun, , South Korea

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Incheon, , 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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Yangsan, , South Korea

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Barcelona, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Winterthur, , Switzerland

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Zurich, , Switzerland

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , 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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Chiang Mai, , Thailand

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Khon Kaen, , Thailand

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Pathum Thani, , Thailand

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Phisanulok, , Thailand

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Malatya, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Liverpool, , United Kingdom

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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 Austria Brazil Bulgaria Canada Chile China France Germany India Israel Italy Japan Mexico Peru Poland Russia South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

References

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He J, Tsuboi M, Weder W, Chen KN, Hochmair MJ, Shih JY, Lee SY, Lee KY, Nhung NV, Saeteng S, Liu L, Xing L, Gia NH, Murakami S, Han Y, Saavedra MP, Yoon SH, Teixeira CHA, Escriu C, Martinez-Marti A, Blakely CM, Yatabe Y, Dacic S, Rukazenkov Y, Huang X, Dayal A, Chaft JE; NeoADAURA Investigators. Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small Cell Lung Cancer. J Clin Oncol. 2025 Sep 10;43(26):2875-2887. doi: 10.1200/JCO-25-00883. Epub 2025 Jun 2.

Reference Type DERIVED
PMID: 40454705 (View on PubMed)

Murat-Onana ML, Ramalingam SS, Janne PA, Gray JE, Ahn MJ, John T, Yatabe Y, Huang X, Rukazenkov Y, Javey M, Brown H, Li-Sucholeiki X. EGFR mutation testing across the osimertinib clinical program. Lung Cancer. 2025 Jun;204:108549. doi: 10.1016/j.lungcan.2025.108549. Epub 2025 Apr 18.

Reference Type DERIVED
PMID: 40311309 (View on PubMed)

Lee JB, Choi SJ, Shim HS, Park BJ, Lee CY, Sudhaman S, Velichko S, Hong MH, Cho BC, Lim SM. Neoadjuvant and Adjuvant Osimertinib in Stage IA to IIIA, EGFR-Mutant NSCLC (NORA). J Thorac Oncol. 2025 May;20(5):641-650. doi: 10.1016/j.jtho.2024.12.023. Epub 2024 Dec 26.

Reference Type DERIVED
PMID: 39732365 (View on PubMed)

Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol. 2021 Nov;17(31):4045-4055. doi: 10.2217/fon-2021-0549. Epub 2021 Jul 19.

Reference Type DERIVED
PMID: 34278827 (View on PubMed)

Other Identifiers

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2022-502606-33-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-000058-89

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D516AC00001

Identifier Type: -

Identifier Source: org_study_id

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