Anticancer TreatmentPhase 3AURA3NCT02151981
AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
A Phase 3 study testing Chemotherapy and Cross-over to Osimertinib in people with Anticancer Treatment, run by AstraZeneca at 150 sites in 18 countries.
Trial summary
A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Anticancer Treatment
- What is being tested?
- Chemotherapy and Cross-over to Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 421 participants
- Where
- 150 sitesin 18 countries
- Study dates
- 4 Aug 2014to 15 Dec 2023
- 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 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with histologically or cytologically documented NSCLC.
- Locally advanced or metastatic NSCLC
- Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment
- Eligible to receive treatment with the selected doublet-chemotherapy
- Central confirmation of T790M+ mutation status
- World Health Organization (WHO) performance status 0-1
- At least one lesion, not previously irradiated.
Who cannot join
- • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of starting 1st EGFR TKI treatment
- Treatment with more than one prior line of treatment for advanced NSCLC
- Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment
- Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
- Previous treatment with Osimertinib, or a 3rd generation EGFR TKI
- For subjects who cross-over to Osimertinib:
- Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review.
- At least 14 days since last dose of platinum-based doublet chemotherapy
Trial locations and contacts
150 sites in 18 countries.
150 sites in 18 countries
Japan25 sites
Research Site
Akashi-shi, 673-8558
Research Site
Bunkyō City, 113-8431
Research Site
Fukuoka, 812-8582
Research Site
Hirakata-shi, 573-1191
Research Site
Kanazawa, 920-8641
Research Site
Kitaadachi-gun, 362-0806
Research Site
Kobe, 650-0047
Research Site
Kurashiki-shi, 710-8602
Research Site
Kyoto, 606-8507
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 464-8681
Research Site
Natori-shi, 981-1293
Research Site
Niigata, 951-8566
Research Site
Okayama, 700-8558
Research Site
Osaka, 534-0021
Research Site
Osaka, 541-8567
Research Site
Sakaishi, 591-8555
Research Site
Sayama, 589-8511
Research Site
Shinjuku-ku, 160-0023
Research Site
Sunto-gun, 411-8777
Research Site
Takatsuki-shi, 569-8686
Research Site
Wakayama, 641-8510
Research Site
Yokohama, 236-0024
Research Site
Yokohama, 236-0051
Research Site
Yokohama, 241-8515
United States21 sites
Research Site
Anaheim, California, 92801
Research Site
Atlanta, Georgia, 30322
Research Site
Brick, New Jersey, 08724
Research Site
Charleston, South Carolina, 29425
Research Site
Chevy Chase, Maryland, 20815
Research Site
Gainesville, Florida, 32610
Research Site
Hershey, Pennsylvania, 17033-0850
Research Site
Houston, Texas, 77030
Research Site
Indianapolis, Indiana, 46202
Research Site
Lacey, Washington, 98503
Research Site
Lebanon, New Hampshire, 03756
Research Site
Marrero, Louisiana, 70072
Research Site
Milwaukee, Wisconsin, 53226
Research Site
New York, New York, 10032
Research Site
Norwalk, Connecticut, 06856
Research Site
Orange, California, 92868
Research Site
Orlando, Florida, 32804
Research Site
Park Ridge, Illinois, 60068
Research Site
Pembroke Pines, Florida, 33028
Research Site
Santa Rosa, California, 95403
Research Site
Tacoma, Washington, 98405
China16 sites
Research Site
Beijing, 100021
Research Site
Beijing, 100142
Research Site
Changchun, 130000
Research Site
Chongqing, 400038
Research Site
Chongqing, 400042
Research Site
Fuzhou, 350014
Research Site
Guangzhou, 510060
Research Site
Guangzhou, 510100
Research Site
Hangzhou, 310003
Research Site
Harbin, 150049
Research Site
Nanchang, 330006
Research Site
Shanghai, 200030
Research Site
Shanghai, CN-200433
Research Site
Tianjin, 300060
Research Site
Ürümqi, 830000
Research Site
Zhengzhou, 450008
South Korea13 sites
Research Site
Busan, 47392
Research Site
Cheongju-si, 28644
Research Site
Goyang-si, 10408
Research Site
Incheon, 21565
Research Site
Jinju, 660-702
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06591
Research Site
Seoul, 156-707
Research Site
Seoul, 6351
Research Site
Suwon, 16499
Research Site
Ulsan, 44033
Taiwan11 sites
Research Site
Changhua, 500
Research Site
Hsinchu, 300
Research Site
Kaohsiung City, 81362
Research Site
Kaohsiung City, 82445
Research Site
Kaohsiung City, 83301
Research Site
Taichung, 40447
Research Site
Taichung, 40705
Research Site
Tainan, 704
Research Site
Taipei, 10002
Research Site
Taipei, 112
Research Site
Taoyuan, 333
United Kingdom11 sites
Research Site
Aberdeen, AB2 2ZB
Research Site
Bristol, BS2 8ED
Research Site
Edinburgh, EH4 2XU
Research Site
Glasgow, G12 0YN
Research Site
Huddersfield, HD3 3EA
Research Site
London, SW10 9NH
Research Site
London, W1G 6AD
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN
Research Site
Nottingham, NG5 1PB
Research Site
Wolverhampton, WV10 0QP
France8 sites
Research Site
Clermont-Ferrand, 63003
Research Site
Dijon, 21079
Research Site
Lille, 59000
Research Site
Marseille, 13915
Research Site
Paris, 75020
Research Site
Strasbourg, 67091
Research Site
Toulouse, 31059
Research Site
Villejuif, 94800
Canada6 sites
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Halifax, Nova Scotia, B3H 1V7
Research Site
Montreal, Quebec, H2L 4M1
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 4E6
Germany6 sites
Research Site
Essen, 45122
Research Site
Frankfurt, 60590
Research Site
Gerlingen, 70839
Research Site
Oldenburg, 26121
Research Site
Regensburg, 93053
Research Site
Würzburg, 97080
Russia6 sites
Research Site
Moscow, 115478
Research Site
Omsk, 644013
Research Site
Saint Petersburg, 197183
Research Site
Saint Petersburg, 197342
Research Site
Saint Petersburg, 197758
Research Site
Yekaterinburg, 620905
Spain6 sites
Research Site
Madrid, 08035
Research Site
Madrid, 28034
Research Site
Madrid, 28041
Research Site
Málaga, 29010
Research Site
Seville, 41013
Research Site
Zaragoza, 50009
Australia5 sites
Research Site
Darlinghurst, 2010
Research Site
Heidelberg, 3084
Research Site
Kogarah, 2217
Research Site
Nedlands, 6009
Research Site
Woolloongabba, 4102
Italy5 sites
Research Site
Avellino, 83100
Research Site
Meldola, 47014
Research Site
Milan, 20133
Research Site
Orbassano, 10043
Research Site
Roma, 00128
Netherlands3 sites
Research Site
Amsterdam, 1066 CX
Research Site
Amsterdam, 1081 HV
Research Site
Groningen, 9713 GZ
Sweden3 sites
Research Site
Gothenburg, 413 45
Research Site
Lund, 221 85
Research Site
Stockholm, 171 76
About this study
Official title: A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene (AURA3).
A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene
Read the detailed description
This is a phase III, open label, randomized study assessing Osimertinib (80 mg, orally, once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for central confirmation of T790 mutation status following confirmed disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will then be randomized to receive either Osimertinib (80mg orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (Osimertinib: platinum-based doublet chemotherapy) ratio. Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. The primary objective of the study is to assess the efficacy of Osimertinib compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded Independent Central Review (BICR).
- Conditions
- Anticancer Treatment
- Being tested
- Chemotherapy, Cross-over to Osimertinib
- Keywords
- Advanced Non-Small Cell Lung Cancer; T790M Mutation Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChemotherapyDrug
Also called Osimertinib, Platinum-based Doublet-Chemotherapy
Randomization to either Osimertinib or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (Osimertinib:platinum-based doublet-chemotherapy) ratio
Cross-over to OsimertinibDrug
Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator.
Subjects who stop platinum-based doublet chemotherapy for reasons other than objective disease progression according to RECIST 1.1 will not be eligible to cross-over to Osimertinib.
| Study group | Role | What they receive |
|---|---|---|
| Osimertinib | Experimental | Osimertinib 80 mg, orally, once daily Receives: Drug: Chemotherapy; Drug: Cross-over to Osimertinib |
| Platinum-based doublet chemotherapy | Active comparator | pemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2 Receives: Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) by Investigator Assessment
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (by investigator assessment) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcomes (5)
Objective Response Rate (ORR) by Investigator Assessment
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Duration of Response (DoR) by Investigator Assessment
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Disease Control Rate (DCR) by Investigator Assessment
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. DCR is the percentage of patients with best response of CR, PR or SD at >=6 weeks, prior to any progressive disease (PD).
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Tumour Shrinkage by Investigator Assessment
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Tumour size was calculated as the sum of the longest diameters (SLD) of the Target Lesions. Tumour shrinkage is percentage change in tumour size from baseline using RECIST v1.1 tumour response.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary: Overall Survival (OS)
Measured: From date of randomization until time of final OS analysis, a median follow-up of 43 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study start4 Aug 2014
- Primary completion15 Apr 2016
- Study completion15 Dec 2023
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 (13)Papers the sponsor has linked to this study.
- Other trials for Anticancer TreatmentStudies 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
- None (open label)
- Enrolment
- 421 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yilong Wu, MD, Principal investigator, Guangdong General Hospital, Guangdong, 510030, ChinaVassiliki A Papadimitrakopoulou, MD, Principal investigator, The University of Texas/M.D. Anderson Cancer Center, Houston, Tx, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02151981
- Sponsor's protocol ID
- D5160C00003
- Other IDs
- 2014-000594-39, 2014
- Acronym
- AURA3
- Status last verified
- Dec 2024
- First submitted
- 15 May 2014
- Last updated
- 7 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- 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
Markovets A, Merino Vega D, Abbosh C, Quinn K, Chang K, Wienke S, Hartmaier R, Barrett JC, Hodgson D. Variability of Circulating Tumor DNA Levels in Plasma Samples From Patients With Advanced Non-Small-Cell Lung Cancer in the Absence of Treatment. JCO Precis Oncol. 2025 Oct;9:e2500287. doi: 10.1200/PO-25-00287. Epub 2025 Oct 30.
PubMed 41166679Murat-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 40311309Gray JE, Markovets A, Reungwetwattana T, Majem M, Nogami N, Peled N, Lee JS, Cho BC, Chewaskulyong B, John T, Han JY, Sebastian M, Todd A, Rukazenkov Y, Barrett C, Chmielecki J, Lee SM, Ramalingam SS, Hartmaier R. Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3. J Thorac Oncol. 2024 Nov;19(11):1525-1538. doi: 10.1016/j.jtho.2024.07.008. Epub 2024 Jul 17.
PubMed 39029876Gray JE, Ahn MJ, Oxnard GR, Shepherd FA, Imamura F, Cheng Y, Okamoto I, Cho BC, Lin MC, Wu YL, Majem M, Gautschi O, Boyer M, Bulusu KC, Markovets A, Barrett JC, Hodge R, McKeown A, Hartmaier RJ, Chmielecki J, Papadimitrakopoulou VA, Ramalingam SS. Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA. Clin Cancer Res. 2023 Sep 1;29(17):3340-3351. doi: 10.1158/1078-0432.CCR-22-3146.
PubMed 37379430King-Kallimanis BL, Bhatnagar V, Horodniceanu EG, Chen TY, Kluetz PG. Timing is everything: The importance of patient-reported outcome assessment frequency when characterizing symptomatic adverse events. Clin Trials. 2022 Jun;19(3):267-273. doi: 10.1177/17407745221093935. Epub 2022 May 15.
PubMed 35575012Singh J, Bourke S, Dyer M, Devlin N, Longworth L. An Analysis of 5-Level Version of EQ-5D Adjusting for Treatment Switching: The Case of Patients With Epidermal Growth Factor Receptor T790M-Positive Nonsmall Cell Lung Cancer Treated With Osimertinib. Value Health. 2022 Jul;25(7):1205-1211. doi: 10.1016/j.jval.2022.01.022. Epub 2022 Apr 2.
PubMed 35379563Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. doi: 10.1016/j.annonc.2020.08.2100. Epub 2020 Aug 27.
PubMed 32861806Papadimitrakopoulou VA, Han JY, Ahn MJ, Ramalingam SS, Delmonte A, Hsia TC, Laskin J, Kim SW, He Y, Tsai CM, Hida T, Maemondo M, Kato T, Jenkins S, Patel S, Huang X, Laus G, Markovets A, Thress KS, Wu YL, Mok T. Epidermal growth factor receptor mutation analysis in tissue and plasma from the AURA3 trial: Osimertinib versus platinum-pemetrexed for T790M mutation-positive advanced non-small cell lung cancer. Cancer. 2020 Jan 15;126(2):373-380. doi: 10.1002/cncr.32503. Epub 2019 Nov 26.
PubMed 31769875Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non-Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. doi: 10.1200/JCO.2018.77.9363. Epub 2018 Jul 30.
PubMed 30059262Lee CK, Novello S, Ryden A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. doi: 10.1200/JCO.2017.77.2293. Epub 2018 May 7.
PubMed 29733770Akamatsu H, Katakami N, Okamoto I, Kato T, Kim YH, Imamura F, Shinkai M, Hodge RA, Uchida H, Hida T. Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial. Cancer Sci. 2018 Jun;109(6):1930-1938. doi: 10.1111/cas.13623. Epub 2018 May 31.
PubMed 29697876Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
PubMed 27959700Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. doi: 10.1016/S1470-2045(15)00121-7. Epub 2015 Jul 6.
PubMed 26159065
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene (AURA3).
- ClinicalTrials.gov ID
- NCT02151981
- Acronym / sponsor ID
- AURA3 / D5160C00003
- Conditions
- Anticancer Treatment
- Keywords
- Advanced Non-Small Cell Lung Cancer; T790M Mutation Positive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 421 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 4 Aug 2014 (actual)
- Primary completion
- 15 Apr 2016 (actual)
- Study completion
- 15 Dec 2023 (actual)
- First posted
- 2 Jun 2014 (estimated)
- Results
- Posted 21 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene
Detailed description
This is a phase III, open label, randomized study assessing Osimertinib (80 mg, orally, once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for central confirmation of T790 mutation status following confirmed disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will then be randomized to receive either Osimertinib (80mg orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (Osimertinib: platinum-based doublet chemotherapy) ratio. Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. The primary objective of the study is to assess the efficacy of Osimertinib compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded Independent Central Review (BICR).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Osimertinib | Experimental | Drug: Chemotherapy, Drug: Cross-over to OsimertinibOsimertinib 80 mg, orally, once daily |
| Platinum-based doublet chemotherapy | Active comparator | Drug: Chemotherapypemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2 |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects with histologically or cytologically documented NSCLC.
- Locally advanced or metastatic NSCLC
- Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment
- Eligible to receive treatment with the selected doublet-chemotherapy
- Central confirmation of T790M+ mutation status
Key exclusion criteria (8 listed)
- • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of starting 1st EGFR TKI treatment
- Treatment with more than one prior line of treatment for advanced NSCLC
- Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment
- Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
- Previous treatment with Osimertinib, or a 3rd generation EGFR TKI
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 |
|---|---|---|
| ChemotherapyAlso: Osimertinib, Platinum-based Doublet-ChemotherapyRandomization to either Osimertinib or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (Osimertinib:platinum-based doublet-chemotherapy) ratio | Drug | Osimertinib, Platinum-based doublet chemotherapy |
| Cross-over to OsimertinibOnce subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. Subjects who stop platinum-based doublet chemotherapy for reasons other than objective disease progression according to RECIST 1.1 will not be eligible to cross-over to Osimertinib. | Drug | Osimertinib |
Primary outcome
Progression Free Survival (PFS) by Investigator Assessment
Time frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (by investigator assessment) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.
5 secondary outcomes
Objective Response Rate (ORR) by Investigator Assessment
Time frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Duration of Response (DoR) by Investigator Assessment
Time frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Disease Control Rate (DCR) by Investigator Assessment
Time frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Tumour Shrinkage by Investigator Assessment
Time frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary: Overall Survival (OS)
Time frame: From date of randomization until time of final OS analysis, a median follow-up of 43 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41166679Markovets A, Merino Vega D, Abbosh C, Quinn K, Chang K, Wienke S, Hartmaier R, Barrett JC, Hodgson D. Variability of Circulating Tumor DNA Levels in Plasma Samples From Patients With Advanced Non-Small-Cell Lung Cancer in the Absence of Treatment. JCO Precis Oncol. 2025 Oct;9:e2500287. doi: 10.1200/PO-25-00287. Epub 2025 Oct 30.
- 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 39029876Gray JE, Markovets A, Reungwetwattana T, Majem M, Nogami N, Peled N, Lee JS, Cho BC, Chewaskulyong B, John T, Han JY, Sebastian M, Todd A, Rukazenkov Y, Barrett C, Chmielecki J, Lee SM, Ramalingam SS, Hartmaier R. Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3. J Thorac Oncol. 2024 Nov;19(11):1525-1538. doi: 10.1016/j.jtho.2024.07.008. Epub 2024 Jul 17.
- Derived from this study: PubMed 37379430Gray JE, Ahn MJ, Oxnard GR, Shepherd FA, Imamura F, Cheng Y, Okamoto I, Cho BC, Lin MC, Wu YL, Majem M, Gautschi O, Boyer M, Bulusu KC, Markovets A, Barrett JC, Hodge R, McKeown A, Hartmaier RJ, Chmielecki J, Papadimitrakopoulou VA, Ramalingam SS. Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA. Clin Cancer Res. 2023 Sep 1;29(17):3340-3351. doi: 10.1158/1078-0432.CCR-22-3146.
- Derived from this study: PubMed 35575012King-Kallimanis BL, Bhatnagar V, Horodniceanu EG, Chen TY, Kluetz PG. Timing is everything: The importance of patient-reported outcome assessment frequency when characterizing symptomatic adverse events. Clin Trials. 2022 Jun;19(3):267-273. doi: 10.1177/17407745221093935. Epub 2022 May 15.
- Derived from this study: PubMed 35379563Singh J, Bourke S, Dyer M, Devlin N, Longworth L. An Analysis of 5-Level Version of EQ-5D Adjusting for Treatment Switching: The Case of Patients With Epidermal Growth Factor Receptor T790M-Positive Nonsmall Cell Lung Cancer Treated With Osimertinib. Value Health. 2022 Jul;25(7):1205-1211. doi: 10.1016/j.jval.2022.01.022. Epub 2022 Apr 2.
- Derived from this study: PubMed 32861806Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. doi: 10.1016/j.annonc.2020.08.2100. Epub 2020 Aug 27.
- Derived from this study: PubMed 31769875Papadimitrakopoulou VA, Han JY, Ahn MJ, Ramalingam SS, Delmonte A, Hsia TC, Laskin J, Kim SW, He Y, Tsai CM, Hida T, Maemondo M, Kato T, Jenkins S, Patel S, Huang X, Laus G, Markovets A, Thress KS, Wu YL, Mok T. Epidermal growth factor receptor mutation analysis in tissue and plasma from the AURA3 trial: Osimertinib versus platinum-pemetrexed for T790M mutation-positive advanced non-small cell lung cancer. Cancer. 2020 Jan 15;126(2):373-380. doi: 10.1002/cncr.32503. Epub 2019 Nov 26.
- Derived from this study: PubMed 30059262Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non-Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. doi: 10.1200/JCO.2018.77.9363. Epub 2018 Jul 30.
- Derived from this study: PubMed 29733770Lee CK, Novello S, Ryden A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. doi: 10.1200/JCO.2017.77.2293. Epub 2018 May 7.
- Derived from this study: PubMed 29697876Akamatsu H, Katakami N, Okamoto I, Kato T, Kim YH, Imamura F, Shinkai M, Hodge RA, Uchida H, Hida T. Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial. Cancer Sci. 2018 Jun;109(6):1930-1938. doi: 10.1111/cas.13623. Epub 2018 May 31.
- Derived from this study: PubMed 27959700Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
- D5160C00003AURA3\_CSPredactedLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- CSR SynopsisLink 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.
Yilong Wu, MD principal investigator
Guangdong General Hospital, Guangdong, 510030, China
Vassiliki A Papadimitrakopoulou, MD principal investigator
The University of Texas/M.D. Anderson Cancer Center, Houston, Tx, USA
150 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chemotherapy and Cross-over to Osimertinib in people with Anticancer Treatment, run by AstraZeneca at 150 sites in 18 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 7 inclusion and 8 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: finished, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 150 sites in Japan, United States, China, South Korea, Taiwan and 13 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. 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 21 Jul 2017). 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?
Progression Free Survival (PFS) by Investigator Assessment (time frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).). 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 NCT02151981, which also lists 13 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 7 Jan 2025.