Non-Small Cell Lung CancerPhase 3NeoADAURANCT04351555
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
A Phase 3 study testing Osimertinib, Cisplatin and Carboplatin in people with Non-Small Cell Lung Cancer, run by AstraZeneca at 158 sites in 25 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Osimertinib, Cisplatin and Carboplatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 358 participants
- Where
- 158 sitesin 25 countries
- Study dates
- 16 Dec 2020to 13 Jun 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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)
Trial locations and contacts
158 sites in 25 countries.
158 sites in 25 countries
China26 sites
Research Site
Beijing, 100142
Research Site
Beijing, 100191
Research Site
Beijing, CN-100730
Research Site
Changsha, 410008
Research Site
Changsha, 410013
Research Site
Chengdu, 610041
Research Site
Chongqing, 400037
Research Site
Guangzhou, 510062
Research Site
Guangzhou, 510095
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Guangzhou, 510120
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Guangzhou, 510515
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Hangzhou, 310009
Research Site
Hangzhou, 310022
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Kunming, 650118
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Nanchang, 330006
Research Site
Nantong, 226001
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Shandong
Research Site
Shanghai, 200030
Research Site
Shanghai, 200032
Research Site
Shanghai, 200433
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Suzhou, 215006
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Ürümqi, 830000
Research Site
Wanzhou, 404000
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Wenzhou, CN-325000
Research Site
Xiamen, 361004
Research Site
Yangzhou, 225001
Japan15 sites
Research Site
Akashi-shi, 673-8558
Research Site
Bunkyō City, 113-8431
Research Site
Chiba, 260-8677
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Hiroshima, 734-8551
Research Site
Kashiwa, 227-8577
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Kōtoku, 135-8550
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Kyoto, 606-8507
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Niigata, 951-8566
Research Site
Osaka, 541-8567
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Sakai, 590-0197
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Sakaishi, 591-8555
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Sendai, 981-0914
Research Site
Shinjuku-ku, 160-0023
Research Site
Sunto-gun, 411-8777
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Yokohama, 241-8515
United States12 sites
Research Site
Boston, Massachusetts, 02215
Research Site
Commack, New York, 11725
Research Site
Duarte, California, 91010
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Fairfax, Virginia, 22031
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Houston, Texas, 77030
Research Site
Irvine, California, 92618
Research Site
Lebanon, New Hampshire, 03756
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New York, New York, 10032
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San Francisco, California, 94143
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Santa Monica, California, 90404
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Santa Rosa, California, 95403
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Seattle, Washington, 98104
Brazil12 sites
Research Site
Barretos, 14784-400
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Fortaleza, 60135-040
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Jaú, 17204310
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Porto Alegre, 90035-000
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Porto Alegre, 90610-000
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Recife, 52010-075
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Rio de Janeiro, 22271-110
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Santa Maria, 97015-450
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São José do Rio Preto, 15090-000
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São Paulo, 01327-001
Research Site
São Paulo, 04038-034
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São Paulo, 04501-000
Germany10 sites
Research Site
Berlin, 12351
Research Site
Bielefeld, 33611
Research Site
Cologne, 51109
Research Site
Esslingen a.N., 73730
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Freiburg im Breisgau, 79106
Research Site
Gauting, 82131
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Georgsmarienhütte, 49124
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Halle, 06120
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Oldenburg, 26121
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Würzburg, 97067
Russia8 sites
Research Site
Kazan', 420029
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Krasnoyarsk, 660133
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Moscow, 105229
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Nizhny Novgorod, 603081
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Obninsk, 249036
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Perm, 614990
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Saint Petersburg, 191036
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Saint Petersburg, 197758
Italy7 sites
Research Site
Bari, 70124
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Florence, 50134
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Monza, 20900
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Orbassano, 10043
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Padova, 35128
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Rozzano, 20089
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Varese, 21100
South Korea7 sites
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Daegu, 41404
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Hwasun-gun, 58128
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Incheon, 21431
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Seoul, 02447
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Seoul, 08308
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Seoul, 42601
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Yangsan, 50612
Taiwan7 sites
Research Site
Taichung, 40201
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Taichung, 40447
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Tainan, 73657
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Taipei, 10002
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Taipei, 110
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Taipei, 112
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Taipei, 235
Israel6 sites
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Haifa, 3109601
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Jerusalem, 91120
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Kfar Saba, 95847
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Petah Tikva, 49100
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Ramat Gan, 5265601
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Tel Aviv, 62748
Thailand6 sites
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Bangkok, 10330
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Bangkok, 10400
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Chiang Mai, 50200
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Khon Kaen, 40002
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Pathum Thani, 12120
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Phisanulok, 65000
Turkey (Türkiye)6 sites
Research Site
Ankara, 06010
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Ankara, 06800
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Ankara, 6500
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Istanbul, 34010
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Istanbul, 34214
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Malatya, 44280
Peru5 sites
Research Site
La Libertad, 13013
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Lima, 0051
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Lima, 15036
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Lima, L41
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Lima, LIMA 34
India4 sites
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Mumbai, 400012
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Namakkal, 637001
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New Delhi, 110029
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Varanasi, 221005
Spain4 sites
Research Site
Barcelona, 08035
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Madrid, 28040
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Majadahonda, 28222
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Málaga, 29010
Bulgaria3 sites
Research Site
Panagyurishte, 4500
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Pleven, 5804
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Sofia, 1113
Chile3 sites
Research Site
Las Condes, 7560908
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Santiago, 7500713
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Santiago, 7500921
Mexico3 sites
Research Site
Aguascalientes, 20230
Research Site
D.F, 14050
Research Site
Mexico City, '14080
Vietnam3 sites
Research Site
Hanoi, 100000
Research Site
Ho Chi Minh City, 700000
Research Site
Ho Chi Minh City, 70000
Canada2 sites
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Toronto, Ontario, M5G 2N2
Switzerland2 sites
Research Site
Winterthur, 8401
Research Site
Zurich, CH-8091
United Kingdom2 sites
Research Site
Birmingham, B9 5SS
Research Site
Liverpool, L7 8YA
About this study
Official title: 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
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Osimertinib, Cisplatin, Carboplatin, Placebo, Pemetrexed
- Keywords
- Resectable; NSCLC; Osimertinib; EGFRm Positive; Neoadjuvant; Adjuvant
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OsimertinibDrug
Also called AZD9291; TAGRISSO
Oral
CisplatinDrug
Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
CarboplatinDrug
Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
PlaceboDrug
Oral
PemetrexedDrug
Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Cisplatin; Drug: Carboplatin; Drug: Placebo; Drug: 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) Receives: Drug: Osimertinib; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed |
| Arm 3: Osimertinib monotherapy | Experimental | Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) Receives: Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Pathological Response (MPR) - IASLC Method
Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (IASLC method). Patients will only be considered to have an MPR if they also have an R0 margin result.
Measured: From date of randomization to an average of 12 weeks after the first dose
Major Pathological Response (MPR) - Chemotherapy Method
Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (chemotherapy method). Patients will only be considered to have an MPR if they also have an R0 margin result.
Measured: From date of randomization to an average of 12 weeks after the first dose
Secondary outcomes (9)
Pathological Complete Response (pCR) - IASLC Method
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 using IASLC method. Patients will only be considered to have pCR if they also have an R0 margin result based on site assessment.
Measured: From date of randomization to an average of 12 weeks after the first dose
Pathological Complete Response (pCR) - Chemotherapy Method
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 using chemotherapy method. Patients will only be considered to have pCR if they also have an R0 margin result based on site assessment.
Measured: From date of randomization to an average of 12 weeks after the first dose
Downstaging
Measured using pathologic mediastinal lymph node evaluation. Pathological downstaging is defined as baseline N2 patients becoming N1/N0 or N1 to N0 at the time of surgery. Only patients with pathological staging at both baseline and surgery are included in this analysis.
Measured: From date of randomization to an average of 12 weeks after the first dose.
Concordance of EGFRm Status Between Tumor Tissue DNA and Patient-matched Plasma-derived ctDNA (Mutation Ex19Del or L858R)
Comparing the baseline central cobas® EGFR Mutation Test V2 between tumor tissue DNA and matched plasma ctDNA results (excluding invalid results). Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.
Measured: Screening/Baseline
Concordance of EGFR Mutation Status Between the Local and Central Test Results From Baseline Tumor Samples (Mutation Ex19Del or L858R)
Comparing the local EGFR mutation test result used for patient selection with the retrospective baseline central cobas® EGFR Mutation Test V2 results (excluding invalid results). Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.
Measured: Screening/Baseline
Change From Baseline in EORTC QLQ-C30 Primary Subscale Scores (Neoadjuvant Period)
Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (random effect), treatment, visit (fixed effect \& repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-C30 has 30 questions and questions are combined to produce symptom scales, individual symptom items, functional scales, and global health status (GHS)/quality of life (QoL). Each of the scale/items range from 0-100 after a linear transformation. Positive change from baseline scores on the GHS/QoL and functioning scales indicate improvement on health status/function, and negative change scores on symptom scales/items represent less symptom severity/improvement on symptom status.
Measured: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days ).
Change From Baseline in EORTC QLQ-LC13 Primary Subscale Scores (Neoadjuvant Period)
Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (as a random effect), treatment, visit (as fixed effect and repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Questions assess cough, hemoptysis, dyspnea, site specific pain, sore mouth, dysphagia, peripheral neuropathy, and alopecia and pain medication. While the QLQ-LC13 includes more scales, only the Coughing, Pain in chest, and Dyspnea subscale scores were analyzed for this endpoint.
Negative change from baseline scores indicates less symptom severity, and thus improvement on health status.
Measured: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days).
PK Plasma Concentrations of Osimertinib
Summary of plasma concentrations (nM) of Osimertinib
Measured: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
PK Plasma Concentrations of AZ5104
Summary of plasma concentrations (nM) of AZ5104
Measured: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2020
- Study start16 Dec 2020
- Primary completion15 Oct 2024
- Study completion13 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 358 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jamie Chaft, MD, Principal investigator, Memorial Sloan Kettering, USAkeiju Aokage, MD, Principal investigator, National Cancer Center Hospital East, JapanWalter Weder, MD, Principal investigator, Thoraxchirurgie Bethanien, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04351555
- Sponsor's protocol ID
- D516AC00001
- Other IDs
- 2022-502606-33-00, 2020-000058-89
- Acronym
- NeoADAURA
- Status last verified
- Aug 2026
- First submitted
- 1 Apr 2020
- Last updated
- 9 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40454705Murat-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.
PubMed 40311309Lee 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.
PubMed 39732365Tsuboi 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.
PubMed 34278827