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 (NeoADAURA)

A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Estimated): 328
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com
• Study Contact Backup: Name: AstraZeneca Cancer Study Locator; Phone Number: 1-877-400-4656; Email: astrazeneca@emergingmed.com

Study Locations

• Austria
  • Graz, Austria, 8036
    • Active, not recruiting
    • Research Site
  • Linz, Austria, 4020
    • Withdrawn
    • Research Site
  • Vienna, Austria
    • Withdrawn
    • Research Site
  • Wien, Austria, 1210
    • Active, not recruiting
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Active, not recruiting
    • Research Site
  • Belo Horizonte, Brazil, 30110-022
    • Withdrawn
    • Research Site
  • Bento Goncalves, Brazil, 95700-084
    • Withdrawn
    • Research Site
  • Fortaleza, Brazil, 60135-040
    • Active, not recruiting
    • Research Site
  • Jau, Brazil, 17204310
    • Active, not recruiting
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Active, not recruiting
    • Research Site
  • Porto Alegre, Brazil, 90035-000
    • Active, not recruiting
    • Research Site
  • Recife, Brazil, 52010-075
    • Active, not recruiting
    • Research Site
  • Ribeirão Preto, Brazil, 14021-636
    • Withdrawn
    • Research Site
  • Rio de Janeiro, Brazil, 22271-110
    • Active, not recruiting
    • Research Site
  • Santa Maria, Brazil, 97015-450
    • Active, not recruiting
    • Research Site
  • Sao Paulo, Brazil, 01321-001
    • Withdrawn
    • Research Site
  • Sao Paulo, Brazil, 01327-001
    • Active, not recruiting
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 04038-034
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 04501-000
    • Active, not recruiting
    • Research Site
• Bulgaria
  • Panagyurishte, Bulgaria, 4500
    • Active, not recruiting
    • Research Site
  • Pleven, Bulgaria, 5804
    • Active, not recruiting
    • Research Site
  • Plovdiv, Bulgaria, 4004
    • Withdrawn
    • Research Site
  • Sofia, Bulgaria, 1407
    • Withdrawn
    • Research Site
  • Sofia, Bulgaria, 1527
    • Withdrawn
    • Research Site
  • Sofia, Bulgaria, 1618
    • Withdrawn
    • Research Site
  • Sofia, Bulgaria, 1113
    • Active, not recruiting
    • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Active, not recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Withdrawn
      • Research Site
    • Montreal, Quebec, Canada, H4A 3J1
      • Active, not recruiting
      • Research Site
• Chile
  • Concepcion, Chile, 4070196
    • Withdrawn
    • Research Site
  • Las Condes, Chile, 7560908
    • Active, not recruiting
    • Research Site
  • Santiago, Chile, 7500921
    • Recruiting
    • Research Site
  • Santiago, Chile, 7520349
    • Withdrawn
    • Research Site
  • Santiago, Chile, 7500713
    • Active, not recruiting
    • Research Site
  • Viña del Mar, Chile, 2540488
    • Withdrawn
    • Research Site
• China
  • Beijing, China, 100029
    • Withdrawn
    • Research Site
  • Beijing, China, 100029
    • Recruiting
    • Research Site
  • Beijing, China, 100142
    • Active, not recruiting
    • Research Site
  • Beijing, China, 100191
    • Active, not recruiting
    • Research Site
  • Beijing, China, CN-100730
    • Active, not recruiting
    • Research Site
  • Changchun, China, 130000
    • Withdrawn
    • Research Site
  • Changsha, China, 410013
    • Active, not recruiting
    • Research Site
  • Changsha, China, 410008
    • Active, not recruiting
    • Research Site
  • Chengdu, China, 610041
    • Active, not recruiting
    • Research Site
  • Chongqing, China, 400037
    • Active, not recruiting
    • Research Site
  • Guangzhou, China, 510120
    • Active, not recruiting
    • Research Site
  • Guangzhou, China, 510095
    • Active, not recruiting
    • Research Site
  • Guangzhou, China, 510515
    • Active, not recruiting
    • Research Site
  • Guangzhou, China, 510062
    • Active, not recruiting
    • Research Site
  • Hangzhou, China, 310003
    • Recruiting
    • Research Site
  • Hangzhou, China, 310006
    • Withdrawn
    • Research Site
  • Hangzhou, China, 310022
    • Active, not recruiting
    • Research Site
  • Hangzhou, China, 310009
    • Active, not recruiting
    • Research Site
  • Hefei, China, 230001
    • Withdrawn
    • Research Site
  • Kunming, China, 650118
    • Active, not recruiting
    • Research Site
  • Linhai, China, 317000
    • Recruiting
    • Research Site
  • Nanchang, China, 330006
    • Active, not recruiting
    • Research Site
  • Nanjing, China, 210029
    • Recruiting
    • Research Site
  • Nantong, China, 226001
    • Recruiting
    • Research Site
  • Shandong, China
    • Active, not recruiting
    • Research Site
  • Shanghai, China, 200032
    • Active, not recruiting
    • Research Site
  • Shanghai, China, 200433
    • Active, not recruiting
    • Research Site
  • Shanghai, China, 200030
    • Active, not recruiting
    • Research Site
  • Shenyang, China, 110042
    • Recruiting
    • Research Site
  • Shenzhen, China, 518053
    • Recruiting
    • Research Site
  • Suzhou, China, 215006
    • Active, not recruiting
    • Research Site
  • Urumqi, China, 830000
    • Terminated
    • Research Site
  • Wanzhou, China, 404000
    • Active, not recruiting
    • Research Site
  • Wenzhou, China, CN-325000
    • Active, not recruiting
    • Research Site
  • Xiamen, China, 361004
    • Active, not recruiting
    • Research Site
  • Yangzhou, China, 225001
    • Active, not recruiting
    • Research Site
  • Zhengzhou, China, 450008
    • Withdrawn
    • Research Site
• France
  • Angers, France, 49033
    • Withdrawn
    • Research Site
  • Avignon Cedex, France, 84902
    • Active, not recruiting
    • Research Site
  • Bordeaux, France, 33000
    • Active, not recruiting
    • Research Site
  • Clermont Ferrand, France, 63011
    • Withdrawn
    • Research Site
  • Lyon, France, 69373
    • Withdrawn
    • Research Site
  • Toulon Cedex 9, France, 83800
    • Withdrawn
    • Research Site
• Germany
  • Berlin, Germany, 12351
    • Completed
    • Research Site
  • Bielefeld, Germany, 33611
    • Completed
    • Research Site
  • Esslingen a.N., Germany, 73730
    • Completed
    • Research Site
  • Freiburg, Germany, 79106
    • Active, not recruiting
    • Research Site
  • Gauting, Germany, 82131
    • Completed
    • Research Site
  • Georgsmarienhuette, Germany, 49124
    • Completed
    • Research Site
  • Halle, Germany, 06120
    • Completed
    • Research Site
  • Hamburg, Germany, 21075
    • Withdrawn
    • Research Site
  • Heidelberg, Germany, 69126
    • Withdrawn
    • Research Site
  • Homburg, Germany, 66421
    • Withdrawn
    • Research Site
  • Köln, Germany, 51109
    • Completed
    • Research Site
  • Oldenburg, Germany, 26121
    • Active, not recruiting
    • Research Site
  • Würzburg, Germany, 97067
    • Completed
    • Research Site
• India
  • Delhi, India, 110085
    • Withdrawn
    • Research Site
  • Kolkata, India, 700160
    • Withdrawn
    • Research Site
  • Manipal, India, 576104
    • Withdrawn
    • Research Site
  • Mumbai, India, 400036
    • Withdrawn
    • Research Site
  • Mumbai, India, 400012
    • Active, not recruiting
    • Research Site
  • Namakkal, India, 637001
    • Active, not recruiting
    • Research Site
  • New Delhi, India, 110029
    • Active, not recruiting
    • Research Site
  • Varanasi, India, 221005
    • Active, not recruiting
    • Research Site
• Israel
  • Haifa, Israel, 3109601
    • Completed
    • Research Site
  • Jerusalem, Israel, 91120
    • Completed
    • Research Site
  • Kfar Saba, Israel, 95847
    • Completed
    • Research Site
  • Petah Tikva, Israel, 49100
    • Completed
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Active, not recruiting
    • Research Site
  • Tel Aviv, Israel, 62748
    • Active, not recruiting
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Active, not recruiting
    • Research Site
  • Firenze, Italy, 50134
    • Terminated
    • Research Site
  • Monza, Italy, 20900
    • Active, not recruiting
    • Research Site
  • Orbassano, Italy, 10043
    • Active, not recruiting
    • Research Site
  • Padova, Italy, 35128
    • Terminated
    • Research Site
  • Roma, Italy, 00144
    • Withdrawn
    • Research Site
  • Rozzano, Italy, 20089
    • Active, not recruiting
    • Research Site
  • Varese, Italy, 21100
    • Terminated
    • Research Site
• Japan
  • Akashi-shi, Japan, 673-8558
    • Active, not recruiting
    • Research Site
  • Bunkyo-ku, Japan, 113-8431
    • Active, not recruiting
    • Research Site
  • Chiba-shi, Japan, 260-8677
    • Active, not recruiting
    • Research Site
  • Hiroshima-shi, Japan, 734-8551
    • Active, not recruiting
    • Research Site
  • Kashiwa, Japan, 227-8577
    • Active, not recruiting
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Active, not recruiting
    • Research Site
  • Kyoto-shi, Japan, 606-8507
    • Active, not recruiting
    • Research Site
  • Niigata-shi, Japan, 951-8566
    • Active, not recruiting
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Active, not recruiting
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Active, not recruiting
    • Research Site
  • Sakai-shi, Japan, 591-8555
    • Recruiting
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Active, not recruiting
    • Research Site
  • Shinjuku-ku, Japan, 160-0023
    • Active, not recruiting
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Active, not recruiting
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Active, not recruiting
    • Research Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Active, not recruiting
    • Research Site
  • Hwasun-gun, Korea, Republic of, 58128
    • Suspended
    • Research Site
  • Incheon, Korea, Republic of, 21431
    • Active, not recruiting
    • Research Site
  • Seoul, Korea, Republic of, 05030
    • Withdrawn
    • Research Site
  • Seoul, Korea, Republic of, 02447
    • Active, not recruiting
    • Research Site
  • Seoul, Korea, Republic of, 08308
    • Active, not recruiting
    • Research Site
  • Seoul, Korea, Republic of, 42601
    • Active, not recruiting
    • Research Site
  • Yangsan-si, Korea, Republic of, 50612
    • Active, not recruiting
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Active, not recruiting
    • Research Site
  • D.F, Mexico, 14050
    • Active, not recruiting
    • Research Site
  • Mexico City, Mexico, 06720
    • Withdrawn
    • Research Site
  • Mexico City, Mexico, '14080
    • Active, not recruiting
    • Research Site
• Peru
  • La Libertad, Peru, 13013
    • Completed
    • Research Site
  • Lima, Peru, LIMA 32
    • Withdrawn
    • Research Site
  • Lima, Peru, 15038
    • Withdrawn
    • Research Site
  • Lima, Peru, 0051
    • Completed
    • Research Site
  • Lima, Peru, 15036
    • Completed
    • Research Site
  • Lima, Peru, L41
    • Completed
    • Research Site
  • Lima, Peru, LIMA 34
    • Completed
    • Research Site
• Poland
  • Białystok, Poland, 15-540
    • Withdrawn
    • Research Site
  • Kraków, Poland, 31-202
    • Withdrawn
    • Research Site
  • Olsztyn, Poland, 10-357
    • Active, not recruiting
    • Research Site
  • Otwock, Poland, 05-400
    • Withdrawn
    • Research Site
  • Poznań, Poland, 60-569
    • Recruiting
    • Research Site
  • Szczecin, Poland, 71-455
    • Withdrawn
    • Research Site
  • Warszawa, Poland, 04-141
    • Recruiting
    • Research Site
  • Warszawa, Poland, 02-781
    • Withdrawn
    • Research Site
  • Wrocław, Poland, 53-439PL
    • Withdrawn
    • Research Site
• Russian Federation
  • Kazan, Russian Federation, 420029
    • Suspended
    • Research Site
  • Krasnoyarsk, Russian Federation, 660133
    • Terminated
    • Research Site
  • Moscow, Russian Federation, 121205
    • Withdrawn
    • Research Site
  • Moscow, Russian Federation, 105229
    • Terminated
    • Research Site
  • Nizhniy Novgorod, Russian Federation, 603081
    • Suspended
    • Research Site
  • Obninsk, Russian Federation, 249036
    • Terminated
    • Research Site
  • Perm, Russian Federation, 614990
    • Terminated
    • Research Site
  • Saint Petersburg, Russian Federation, 191036
    • Suspended
    • Research Site
  • Saint Petersburg, Russian Federation, 197758
    • Terminated
    • Research Site
  • Saint-Petersburg, Russian Federation, 197758
    • Terminated
    • Research Site
  • St. Petersburg, Russian Federation, 197022
    • Withdrawn
    • Research Site
  • Tomsk, Russian Federation, 634063
    • Withdrawn
    • Research Site
• Singapore
  • Singapore, Singapore, 308433
    • Withdrawn
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • Research Site
  • Barcelona, Spain, 08036
    • Withdrawn
    • Research Site
  • Madrid, Spain, 28040
    • Active, not recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Terminated
    • Research Site
  • Majadahonda, Spain, 28222
    • Active, not recruiting
    • Research Site
  • Málaga, Spain, 29010
    • Terminated
    • Research Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Withdrawn
    • Research Site
  • Winterthur, Switzerland, 8401
    • Completed
    • Research Site
  • Zürich, Switzerland, CH-8091
    • Active, not recruiting
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Terminated
    • Research Site
  • Taichung, Taiwan, 40201
    • Active, not recruiting
    • Research Site
  • Tainan City, Taiwan, 73657
    • Active, not recruiting
    • Research Site
  • Taipei, Taiwan, 10002
    • Active, not recruiting
    • Research Site
  • Taipei, Taiwan, 112
    • Active, not recruiting
    • Research Site
  • Taipei, Taiwan, 235
    • Active, not recruiting
    • Research Site
  • Taipei City, Taiwan, 110
    • Active, not recruiting
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Active, not recruiting
    • Research Site
  • Bangkok, Thailand, 10400
    • Active, not recruiting
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Active, not recruiting
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Active, not recruiting
    • Research Site
  • Pathumthani, Thailand, 12120
    • Active, not recruiting
    • Research Site
  • Pathumwan, Thailand, 10330
    • Withdrawn
    • Research Site
  • Phisanulok, Thailand, 65000
    • Active, not recruiting
    • Research Site
• Turkey
  • Ankara, Turkey, 06010
    • Active, not recruiting
    • Research Site
  • Ankara, Turkey, 06800
    • Active, not recruiting
    • Research Site
  • Ankara, Turkey, 6500
    • Active, not recruiting
    • Research Site
  • Istanbul, Turkey, 34010
    • Active, not recruiting
    • Research Site
  • Istanbul, Turkey, 34214
    • Active, not recruiting
    • Research Site
  • Izmir, Turkey, 35110
    • Withdrawn
    • Research Site
  • Malatya, Turkey, 44280
    • Active, not recruiting
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Active, not recruiting
    • Research Site
  • Liverpool, United Kingdom, L7 8YA
    • Active, not recruiting
    • Research Site
  • Manchester, United Kingdom, M23 9LT
    • Active, not recruiting
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Withdrawn
      • Research Site
  • California
    • Duarte, California, United States, 91010
      • Active, not recruiting
      • Research Site
    • Irvine, California, United States, 92618
      • Active, not recruiting
      • Research Site
    • Los Angeles, California, United States, 90048
      • Withdrawn
      • Research Site
    • San Francisco, California, United States, 94143
      • Active, not recruiting
      • Research Site
    • Santa Monica, California, United States, 90404
      • Active, not recruiting
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Active, not recruiting
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Withdrawn
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Withdrawn
      • Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • Withdrawn
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Withdrawn
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Active, not recruiting
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Withdrawn
      • Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Active, not recruiting
      • Research Site
  • New York
    • Commack, New York, United States, 11725
      • Active, not recruiting
      • Research Site
    • New York, New York, United States, 10032
      • Active, not recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Withdrawn
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Active, not recruiting
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Active, not recruiting
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Active, not recruiting
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Active, not recruiting
    • Research Site
  • Ho Chi Minh, Vietnam, 70000
    • Active, not recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1: Placebo with platinum-based chemotherapy; Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)	Drug: Placebo; Oral; Drug: Cisplatin; Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.; Drug: Carboplatin; Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles; Drug: Pemetrexed; Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
Experimental: 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)	Drug: Cisplatin; Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.; Drug: Carboplatin; Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles; Drug: Pemetrexed; Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles; Drug: Osimertinib; Oral; Other Names: AZD9291; TAGRISSO
Experimental: Arm 3: Osimertinib monotherapy; Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)	Drug: Osimertinib; Oral; Other Names: AZD9291; TAGRISSO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Downstaging	Measured using pathologic mediastinal lymph node evaluation	From date of randomization to an average of 12 weeks after the first dose
Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA		Baseline
Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples		Baseline
PK plasma concentrations of osimertinib		From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
Pathological complete response (pCR)	Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery	From date of randomization to an average of 12 weeks after the first dose
Event-free survival (EFS)	An event is defined as documented disease progression that precludes surgery or prevents completion of definitive surgery; recurrence or a new lesion, local or distant (a new primary malignancy, confirmed by pathology if clinically feasible, is not considered to be an EFS event); death due to any cause	From date of randomization up to approximately 5.5 years after the last patient is randomized
Overall Survival (OS)	OS will be defined as the time from the date of randomisation until death due to any cause	From date of randomization up to approximately 5.5 years after the last patient is randomized
Disease free survival (DFS)	DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.	From date of randomization up to approximately 5.5 years after the last patient is randomized
Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items)	Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients	From date of randomization up to approximately 5.5 years after the last patient is randomized
Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items)	Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy	From date of randomization up to approximately 5.5 years after the last patient is randomized

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure rate	The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here 5-year landmark cure rate will be calculated in the same time as OS analysis.	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	Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Estimated): July 5, 2024
• Study Completion (Estimated): June 13, 2029

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Resectable; NSCLC; Osimertinib; EGFRm Positive; Neoadjuvant; Adjuvant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Carboplatin; Osimertinib; Pemetrexed
• Other Study ID Numbers: D516AC00001; 2020-000058-89 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No