NCT04351555

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
358

participants targeted

Target at P25-P50 for phase_3 nonsmall-cell-lung-cancer

Timeline
37mo left

Started Dec 2020

Longer than P75 for phase_3 nonsmall-cell-lung-cancer

Geographic Reach
25 countries

158 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress64%
Dec 2020Jun 2029

First Submitted

Initial submission to the registry

April 1, 2020

Completed
16 days until next milestone

First Posted

Study publicly available on registry

April 17, 2020

Completed
8 months until next milestone

Study Start

First participant enrolled

December 16, 2020

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 15, 2024

Completed
4.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 13, 2029

Expected
Last Updated

May 23, 2025

Status Verified

May 1, 2025

Enrollment Period

3.8 years

First QC Date

April 1, 2020

Last Update Submit

May 22, 2025

Conditions

Keywords

Resectable; NSCLC; Osimertinib; EGFRm Positive; Neoadjuvant; Adjuvant

Outcome Measures

Primary Outcomes (1)

  • Major Pathological Response (MPR)

    Defined as ≤10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery

    From date of randomization to an average of 12 weeks after the first dose

Secondary Outcomes (10)

  • Pathological complete response (pCR)

    From date of randomization to an average of 12 weeks after the first dose

  • Event-free survival (EFS)

    From date of randomization up to approximately 5.5 years after the last patient is randomized

  • Overall Survival (OS)

    From date of randomization up to approximately 5.5 years after the last patient is randomized

  • Disease free survival (DFS)

    From date of randomization up to approximately 5.5 years after the last patient is randomized

  • Downstaging

    From date of randomization to an average of 12 weeks after the first dose

  • +5 more secondary outcomes

Other Outcomes (3)

  • Cure rate

    From the surgery until 5 years after surgery

  • Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone

    From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery

  • MPR using plasma-derived circulating-free tumour DNA (ctDNA)

    From date of randomization to an average of 12 weeks after the first dose

Study Arms (3)

Arm 1: Placebo with platinum-based chemotherapy

PLACEBO COMPARATOR

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

Drug: CisplatinDrug: CarboplatinDrug: PlaceboDrug: Pemetrexed

Arm 2: Osimertinib with platinum-based chemotherapy

EXPERIMENTAL

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)

Drug: OsimertinibDrug: CisplatinDrug: CarboplatinDrug: Pemetrexed

Arm 3: Osimertinib monotherapy

EXPERIMENTAL

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

Drug: Osimertinib

Interventions

Oral

Also known as: AZD9291; TAGRISSO
Arm 2: Osimertinib with platinum-based chemotherapyArm 3: Osimertinib monotherapy

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

Arm 1: Placebo with platinum-based chemotherapyArm 2: Osimertinib with platinum-based chemotherapy

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

Arm 1: Placebo with platinum-based chemotherapyArm 2: Osimertinib with platinum-based chemotherapy

Oral

Arm 1: Placebo with platinum-based chemotherapy

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

Arm 1: Placebo with platinum-based chemotherapyArm 2: Osimertinib with platinum-based chemotherapy

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (158)

Research Site

Duarte, California, 91010, United States

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Irvine, California, 92618, United States

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San Francisco, California, 94143, United States

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Santa Monica, California, 90404, United States

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Santa Rosa, California, 95403, United States

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Boston, Massachusetts, 02215, United States

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Lebanon, New Hampshire, 03756, United States

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Commack, New York, 11725, United States

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New York, New York, 10032, United States

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Houston, Texas, 77030, United States

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Fairfax, Virginia, 22031, United States

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Seattle, Washington, 98104, United States

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Graz, 8036, Austria

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Vienna, 1210, Austria

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Barretos, 14784-400, Brazil

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Fortaleza, 60135-040, Brazil

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Jaú, 17204310, Brazil

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Porto Alegre, 90035-000, Brazil

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Porto Alegre, 90610-000, Brazil

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Recife, 52010-075, Brazil

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Rio de Janeiro, 22271-110, Brazil

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Santa Maria, 97015-450, Brazil

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São José do Rio Preto, 15090-000, Brazil

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São Paulo, 01327-001, Brazil

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São Paulo, 04038-034, Brazil

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São Paulo, 04501-000, Brazil

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Panagyurishte, 4500, Bulgaria

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Pleven, 5804, Bulgaria

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Sofia, 1113, Bulgaria

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Toronto, Ontario, M5G 2N2, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Las Condes, 7560908, Chile

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Santiago, 7500713, Chile

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Santiago, 7500921, Chile

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Beijing, 100142, China

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Beijing, 100191, China

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Beijing, CN-100730, China

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Changsha, 410008, China

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Changsha, 410013, China

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Chengdu, 610041, China

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Chongqing, 400037, China

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Guangzhou, 510062, China

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Guangzhou, 510095, China

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Guangzhou, 510120, China

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Guangzhou, 510515, China

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Hangzhou, 310009, China

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Hangzhou, 310022, China

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Kunming, 650118, China

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Nanchang, 330006, China

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Nantong, 226001, China

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Shandong, China

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Shanghai, 200030, China

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Shanghai, 200032, China

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Shanghai, 200433, China

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Suzhou, 215006, China

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Ürümqi, 830000, China

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Wanzhou, 404000, China

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Wenzhou, CN-325000, China

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Xiamen, 361004, China

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Yangzhou, 225001, China

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Avignon, 84902, France

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Bordeaux, 33000, France

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Berlin, 12351, Germany

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Bielefeld, 33611, Germany

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Cologne, 51109, Germany

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Esslingen a.N., 73730, Germany

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Freiburg im Breisgau, 79106, Germany

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Gauting, 82131, Germany

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Georgsmarienhütte, 49124, Germany

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Halle, 06120, Germany

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Oldenburg, 26121, Germany

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Würzburg, 97067, Germany

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Mumbai, 400012, India

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Namakkal, 637001, India

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New Delhi, 110029, India

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Varanasi, 221005, India

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Haifa, 3109601, Israel

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Jerusalem, 91120, Israel

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Kfar Saba, 95847, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5265601, Israel

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Tel Aviv, 62748, Israel

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Bari, 70124, Italy

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Florence, 50134, Italy

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Monza, 20900, Italy

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Orbassano, 10043, Italy

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Padua, 35128, Italy

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Rozzano, 20089, Italy

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Varese, 21100, Italy

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Akashi-shi, 673-8558, Japan

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Bunkyō City, 113-8431, Japan

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Chiba, 260-8677, Japan

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Hiroshima, 734-8551, Japan

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Kashiwa, 227-8577, Japan

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Kōtoku, 135-8550, Japan

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Kyoto, 606-8507, Japan

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Niigata, 951-8566, Japan

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Osaka, 541-8567, Japan

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Osakasayama-shi, 589-8511, Japan

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Sakaishi, 591-8555, Japan

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Sendai, 981-0914, Japan

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Shinjuku-ku, 160-0023, Japan

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Sunto-gun, 411-8777, Japan

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Yokohama, 241-8515, Japan

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Aguascalientes, 20230, Mexico

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D.F, 14050, Mexico

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Mexico City, '14080, Mexico

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La Libertad, 13013, Peru

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Lima, 0051, Peru

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Lima, 15036, Peru

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Lima, L41, Peru

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Lima, LIMA 34, Peru

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Olsztyn, 10-357, Poland

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Kazan', 420029, Russia

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Krasnoyarsk, 660133, Russia

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Moscow, 105229, Russia

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Nizhny Novgorod, 603081, Russia

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Obninsk, 249036, Russia

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Perm, 614990, Russia

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Saint Petersburg, 191036, Russia

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Saint Petersburg, 197758, Russia

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Daegu, 41404, South Korea

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Hwasun-gun, 58128, South Korea

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Incheon, 21431, South Korea

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Seoul, 02447, South Korea

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Seoul, 08308, South Korea

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Seoul, 42601, South Korea

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Yangsan, 50612, South Korea

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Barcelona, 08035, Spain

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Madrid, 28040, Spain

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Majadahonda, 28222, Spain

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Málaga, 29010, Spain

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Winterthur, 8401, Switzerland

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Zurich, CH-8091, Switzerland

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Taichung, 40201, Taiwan

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Taichung, 40447, Taiwan

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Tainan, 73657, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 110, Taiwan

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Taipei, 112, Taiwan

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Taipei, 235, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Chiang Mai, 50200, Thailand

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Khon Kaen, 40002, Thailand

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Pathum Thani, 12120, Thailand

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Phisanulok, 65000, Thailand

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Ankara, 06010, Turkey (Türkiye)

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Ankara, 06800, Turkey (Türkiye)

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Ankara, 6500, Turkey (Türkiye)

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Istanbul, 34010, Turkey (Türkiye)

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Istanbul, 34214, Turkey (Türkiye)

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Malatya, 44280, Turkey (Türkiye)

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Birmingham, B9 5SS, United Kingdom

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Liverpool, L7 8YA, United Kingdom

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Ho Chi Minh City, 70000, Vietnam

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Related Publications (4)

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinibCisplatinCarboplatinPemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic ChemicalsGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Dicarboxylic

Study Officials

  • Jamie Chaft, MD

    Memorial Sloan Kettering, USA

    PRINCIPAL INVESTIGATOR
  • Masahiro Tsuboi, MD

    National Cancer Center Hospital East, Japan

    PRINCIPAL INVESTIGATOR
  • Walter Weder, MD

    Thoraxchirurgie Bethanien, Switzerland

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 1, 2020

First Posted

April 17, 2020

Study Start

December 16, 2020

Primary Completion

October 15, 2024

Study Completion (Estimated)

June 13, 2029

Last Updated

May 23, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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