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
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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.
Show all 10Show fewer
- 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
Research Site
Guangzhou, 510120
Research Site
Guangzhou, 510515
Research Site
Hangzhou, 310009
Research Site
Hangzhou, 310022
Research Site
Kunming, 650118
Research Site
Nanchang, 330006
Research Site
Nantong, 226001
Research Site
Shandong
Research Site
Shanghai, 200030
Research Site
Shanghai, 200032
Research Site
Shanghai, 200433
Research Site
Suzhou, 215006
Research Site
Ürümqi, 830000
Research Site
Wanzhou, 404000
Research Site
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
Research Site
Hiroshima, 734-8551
Research Site
Kashiwa, 227-8577
Research Site
Kōtoku, 135-8550
Research Site
Kyoto, 606-8507
Research Site
Niigata, 951-8566
Research Site
Osaka, 541-8567
Research Site
Sakai, 590-0197
Research Site
Sakaishi, 591-8555
Research Site
Sendai, 981-0914
Research Site
Shinjuku-ku, 160-0023
Research Site
Sunto-gun, 411-8777
Research Site
Yokohama, 241-8515
United States12 sites
Research Site
Boston, Massachusetts, 02215
Research Site
Commack, New York, 11725
Research Site
Duarte, California, 91010
Research Site
Fairfax, Virginia, 22031
Research Site
Houston, Texas, 77030
Research Site
Irvine, California, 92618
Research Site
Lebanon, New Hampshire, 03756
Research Site
New York, New York, 10032
Research Site
San Francisco, California, 94143
Research Site
Santa Monica, California, 90404
Research Site
Santa Rosa, California, 95403
Research Site
Seattle, Washington, 98104
Brazil12 sites
Research Site
Barretos, 14784-400
Research Site
Fortaleza, 60135-040
Research Site
Jaú, 17204310
Research Site
Porto Alegre, 90035-000
Research Site
Porto Alegre, 90610-000
Research Site
Recife, 52010-075
Research Site
Rio de Janeiro, 22271-110
Research Site
Santa Maria, 97015-450
Research Site
São José do Rio Preto, 15090-000
Research Site
São Paulo, 01327-001
Research Site
São Paulo, 04038-034
Research Site
São Paulo, 04501-000
Germany10 sites
Research Site
Berlin, 12351
Research Site
Bielefeld, 33611
Research Site
Cologne, 51109
Research Site
Esslingen a.N., 73730
Research Site
Freiburg im Breisgau, 79106
Research Site
Gauting, 82131
Research Site
Georgsmarienhütte, 49124
Research Site
Halle, 06120
Research Site
Oldenburg, 26121
Research Site
Würzburg, 97067
Russia8 sites
Research Site
Kazan', 420029
Research Site
Krasnoyarsk, 660133
Research Site
Moscow, 105229
Research Site
Nizhny Novgorod, 603081
Research Site
Obninsk, 249036
Research Site
Perm, 614990
Research Site
Saint Petersburg, 191036
Research Site
Saint Petersburg, 197758
Italy7 sites
Research Site
Bari, 70124
Research Site
Florence, 50134
Research Site
Monza, 20900
Research Site
Orbassano, 10043
Research Site
Padova, 35128
Research Site
Rozzano, 20089
Research Site
Varese, 21100
South Korea7 sites
Research Site
Daegu, 41404
Research Site
Hwasun-gun, 58128
Research Site
Incheon, 21431
Research Site
Seoul, 02447
Research Site
Seoul, 08308
Research Site
Seoul, 42601
Research Site
Yangsan, 50612
Taiwan7 sites
Research Site
Taichung, 40201
Research Site
Taichung, 40447
Research Site
Tainan, 73657
Research Site
Taipei, 10002
Research Site
Taipei, 110
Research Site
Taipei, 112
Research Site
Taipei, 235
Israel6 sites
Research Site
Haifa, 3109601
Research Site
Jerusalem, 91120
Research Site
Kfar Saba, 95847
Research Site
Petah Tikva, 49100
Research Site
Ramat Gan, 5265601
Research Site
Tel Aviv, 62748
Thailand6 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Chiang Mai, 50200
Research Site
Khon Kaen, 40002
Research Site
Pathum Thani, 12120
Research Site
Phisanulok, 65000
Turkey (Türkiye)6 sites
Research Site
Ankara, 06010
Research Site
Ankara, 06800
Research Site
Ankara, 6500
Research Site
Istanbul, 34010
Research Site
Istanbul, 34214
Research Site
Malatya, 44280
Peru5 sites
Research Site
La Libertad, 13013
Research Site
Lima, 0051
Research Site
Lima, 15036
Research Site
Lima, L41
Research Site
Lima, LIMA 34
India4 sites
Research Site
Mumbai, 400012
Research Site
Namakkal, 637001
Research Site
New Delhi, 110029
Research Site
Varanasi, 221005
Spain4 sites
Research Site
Barcelona, 08035
Research Site
Madrid, 28040
Research Site
Majadahonda, 28222
Research Site
Málaga, 29010
Bulgaria3 sites
Research Site
Panagyurishte, 4500
Research Site
Pleven, 5804
Research Site
Sofia, 1113
Chile3 sites
Research Site
Las Condes, 7560908
Research Site
Santiago, 7500713
Research Site
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 (5)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, Weder W, Chen KN, Hochmair MJ, Shih JY, Lee SY, Lee KY, Nguyen VN, Saeteng S, Liu L, Xing L, Hoang Gia N, 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. A plain language summary of results from the NeoADAURA study: treatment with osimertinib before surgery for patients with EGFR-mutated non-small cell lung cancer that can be surgically removed. Future Oncol. 2026 Oct 29:1-11. doi: 10.1080/14796694.2026.2739188. Online ahead of print.
PubMed 42954342He 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
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04351555
- Acronym / sponsor ID
- NeoADAURA / D516AC00001
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Resectable; NSCLC; Osimertinib; EGFRm Positive; Neoadjuvant; Adjuvant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 358 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2020 (actual)
- Primary completion
- 15 Oct 2024 (actual)
- Study completion
- 13 Jun 2029 (estimated)
- First posted
- 17 Apr 2020 (actual)
- Results
- Posted 5 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Placebo with platinum-based chemotherapy | Placebo comparator | Drug: Cisplatin, Drug: Carboplatin, Drug: Placebo, Drug: PemetrexedPlacebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) |
| Arm 2: Osimertinib with platinum-based chemotherapy | Experimental | Drug: Osimertinib, Drug: Cisplatin, Drug: Carboplatin, Drug: PemetrexedOsimertinib 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) |
| Arm 3: Osimertinib monotherapy | Experimental | Drug: OsimertinibOsimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OsimertinibAlso: AZD9291; TAGRISSOOral | Drug | Arm 2: Osimertinib with platinum-based chemotherapy, Arm 3: Osimertinib monotherapy |
| CisplatinCisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles. | Drug | Arm 1: Placebo with platinum-based chemotherapy, Arm 2: Osimertinib with platinum-based chemotherapy |
| CarboplatinCarboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles | Drug | Arm 1: Placebo with platinum-based chemotherapy, Arm 2: Osimertinib with platinum-based chemotherapy |
| PlaceboOral | Drug | Arm 1: Placebo with platinum-based chemotherapy |
| PemetrexedPemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles | Drug | Arm 1: Placebo with platinum-based chemotherapy, Arm 2: Osimertinib with platinum-based chemotherapy |
Primary outcome
Major Pathological Response (MPR) - IASLC Method
Time frame: From date of randomization to an average of 12 weeks after the first dose
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.
Major Pathological Response (MPR) - Chemotherapy Method
Time frame: From date of randomization to an average of 12 weeks after the first dose
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.
9 secondary outcomes
Pathological Complete Response (pCR) - IASLC Method
Time frame: From date of randomization to an average of 12 weeks after the first dose
Pathological Complete Response (pCR) - Chemotherapy Method
Time frame: From date of randomization to an average of 12 weeks after the first dose
Downstaging
Time frame: 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)
Time frame: Screening/Baseline
Concordance of EGFR Mutation Status Between the Local and Central Test Results From Baseline Tumor Samples (Mutation Ex19Del or L858R)
Time frame: Screening/Baseline
Change From Baseline in EORTC QLQ-C30 Primary Subscale Scores (Neoadjuvant Period)
Time frame: 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)
Time frame: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days).
PK Plasma Concentrations of Osimertinib
Time frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
PK Plasma Concentrations of AZ5104
Time frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42954342He J, Weder W, Chen KN, Hochmair MJ, Shih JY, Lee SY, Lee KY, Nguyen VN, Saeteng S, Liu L, Xing L, Hoang Gia N, 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. A plain language summary of results from the NeoADAURA study: treatment with osimertinib before surgery for patients with EGFR-mutated non-small cell lung cancer that can be surgically removed. Future Oncol. 2026 Oct 29:1-11. doi: 10.1080/14796694.2026.2739188. Online ahead of print.
- Derived from this study: PubMed 40454705He 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.
- Derived from this study: PubMed 40311309Murat-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.
- Derived from this study: PubMed 39732365Lee 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.
- Derived from this study: PubMed 34278827Tsuboi 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.
- Clinical Study Protocol\_RedactedLink provided by the sponsor.
- Statistical Analysis Plan\_RedactedLink provided by the sponsor.
- CSR Synopsis\_RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jamie Chaft, MD principal investigator
Memorial Sloan Kettering, USA
keiju Aokage, MD principal investigator
National Cancer Center Hospital East, Japan
Walter Weder, MD principal investigator
Thoraxchirurgie Bethanien, Switzerland
158 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 158 sites in China, Japan, United States, Brazil, Germany and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Pathological Response (MPR) - IASLC Method (time frame: From date of randomization to an average of 12 weeks after the first dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04351555, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.