AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
AURA3
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).
2 other identifiers
interventional
421
18 countries
150
Brief 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 mutation within the Epidermal Growth Factor Receptor Gene
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2014
Longer than P75 for phase_3
150 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 15, 2014
CompletedFirst Posted
Study publicly available on registry
June 2, 2014
CompletedStudy Start
First participant enrolled
August 4, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 15, 2016
CompletedResults Posted
Study results publicly available
July 21, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 15, 2023
CompletedJanuary 7, 2025
December 1, 2024
1.7 years
May 15, 2014
April 12, 2017
December 12, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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
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
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
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
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)
From date of randomization until time of final OS analysis, a median follow-up of 43 months
Other Outcomes (2)
Time to First Subsequent Therapy (TFST)
From date of randomisation until time of final OS analysis, a median follow-up of 43 months
Time to Second Subsequent Therapy (TSST)
From date of randomisation until time of final OS analysis, a median follow-up of 43 months
Study Arms (2)
Osimertinib
EXPERIMENTALOsimertinib 80 mg, orally, once daily
Platinum-based doublet chemotherapy
ACTIVE COMPARATORpemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2
Interventions
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
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (150)
Research Site
Anaheim, California, 92801, United States
Research Site
Orange, California, 92868, United States
Research Site
Santa Rosa, California, 95403, United States
Research Site
Norwalk, Connecticut, 06856, United States
Research Site
Gainesville, Florida, 32610, United States
Research Site
Orlando, Florida, 32804, United States
Research Site
Pembroke Pines, Florida, 33028, United States
Research Site
Atlanta, Georgia, 30322, United States
Research Site
Park Ridge, Illinois, 60068, United States
Research Site
Indianapolis, Indiana, 46202, United States
Research Site
Marrero, Louisiana, 70072, United States
Research Site
Chevy Chase, Maryland, 20815, United States
Research Site
Lebanon, New Hampshire, 03756, United States
Research Site
Brick, New Jersey, 08724, United States
Research Site
New York, New York, 10032, United States
Research Site
Hershey, Pennsylvania, 17033-0850, United States
Research Site
Charleston, South Carolina, 29425, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Lacey, Washington, 98503, United States
Research Site
Tacoma, Washington, 98405, United States
Research Site
Milwaukee, Wisconsin, 53226, United States
Research Site
Darlinghurst, 2010, Australia
Research Site
Heidelberg, 3084, Australia
Research Site
Kogarah, 2217, Australia
Research Site
Nedlands, 6009, Australia
Research Site
Woolloongabba, 4102, Australia
Research Site
Edmonton, Alberta, T6G 1Z2, Canada
Research Site
Vancouver, British Columbia, V5Z 4E6, Canada
Research Site
Halifax, Nova Scotia, B3H 1V7, Canada
Research Site
Ottawa, Ontario, K1H 8L6, Canada
Research Site
Toronto, Ontario, M5G 2M9, Canada
Research Site
Montreal, Quebec, H2L 4M1, Canada
Research Site
Beijing, 100021, China
Research Site
Beijing, 100142, China
Research Site
Changchun, 130000, China
Research Site
Chongqing, 400038, China
Research Site
Chongqing, 400042, China
Research Site
Fuzhou, 350014, China
Research Site
Guangzhou, 510060, China
Research Site
Guangzhou, 510100, China
Research Site
Hangzhou, 310003, China
Research Site
Harbin, 150049, China
Research Site
Nanchang, 330006, China
Research Site
Shanghai, 200030, China
Research Site
Shanghai, CN-200433, China
Research Site
Tianjin, 300060, China
Research Site
Ürümqi, 830000, China
Research Site
Zhengzhou, 450008, China
Research Site
Clermont-Ferrand, 63003, France
Research Site
Dijon, 21079, France
Research Site
Lille, 59000, France
Research Site
Marseille, 13915, France
Research Site
Paris, 75020, France
Research Site
Strasbourg, 67091, France
Research Site
Toulouse, 31059, France
Research Site
Villejuif, 94800, France
Research Site
Essen, 45122, Germany
Research Site
Frankfurt, 60590, Germany
Research Site
Gerlingen, 70839, Germany
Research Site
Oldenburg, 26121, Germany
Research Site
Regensburg, 93053, Germany
Research Site
Würzburg, 97080, Germany
Research Site
Hong Kong, Hong Kong
Research Site
Shatin, 00000, Hong Kong
Research Site
Budapest, 1121, Hungary
Research Site
Avellino, 83100, Italy
Research Site
Meldola, 47014, Italy
Research Site
Milan, 20133, Italy
Research Site
Orbassano, 10043, Italy
Research Site
Roma, 00128, Italy
Research Site
Akashi-shi, 673-8558, Japan
Research Site
Bunkyō City, 113-8431, Japan
Research Site
Fukuoka, 812-8582, Japan
Research Site
Hirakata-shi, 573-1191, Japan
Research Site
Kanazawa, 920-8641, Japan
Research Site
Kitaadachi-gun, 362-0806, Japan
Research Site
Kobe, 650-0047, Japan
Research Site
Kurashiki-shi, 710-8602, Japan
Research Site
Kyoto, 606-8507, Japan
Research Site
Matsuyama, 791-0280, Japan
Research Site
Nagoya, 464-8681, Japan
Research Site
Natori-shi, 981-1293, Japan
Research Site
Niigata, 951-8566, Japan
Research Site
Okayama, 700-8558, Japan
Research Site
Osaka, 534-0021, Japan
Research Site
Osaka, 541-8567, Japan
Research Site
Sakaishi, 591-8555, Japan
Research Site
Sayama, 589-8511, Japan
Research Site
Shinjuku-ku, 160-0023, Japan
Research Site
Sunto-gun, 411-8777, Japan
Research Site
Takatsuki-shi, 569-8686, Japan
Research Site
Wakayama, 641-8510, Japan
Research Site
Yokohama, 236-0024, Japan
Research Site
Yokohama, 236-0051, Japan
Research Site
Yokohama, 241-8515, Japan
Research Site
México, 52763, Mexico
Research Site
Oaxaca City, 68000, Mexico
Research Site
Amsterdam, 1066 CX, Netherlands
Research Site
Amsterdam, 1081 HV, Netherlands
Research Site
Groningen, 9713 GZ, Netherlands
Research Site
Moscow, 115478, Russia
Research Site
Omsk, 644013, Russia
Research Site
Saint Petersburg, 197183, Russia
Research Site
Saint Petersburg, 197342, Russia
Research Site
Saint Petersburg, 197758, Russia
Research Site
Yekaterinburg, 620905, Russia
Research Site
Busan, 47392, South Korea
Research Site
Cheongju-si, 28644, South Korea
Research Site
Goyang-si, 10408, South Korea
Research Site
Incheon, 21565, South Korea
Research Site
Jinju, 660-702, South Korea
Research Site
Seongnam-si, 13620, South Korea
Research Site
Seoul, 03722, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 06591, South Korea
Research Site
Seoul, 156-707, South Korea
Research Site
Seoul, 6351, South Korea
Research Site
Suwon, 16499, South Korea
Research Site
Ulsan, 44033, South Korea
Research Site
Madrid, 08035, Spain
Research Site
Madrid, 28034, Spain
Research Site
Madrid, 28041, Spain
Research Site
Málaga, 29010, Spain
Research Site
Seville, 41013, Spain
Research Site
Zaragoza, 50009, Spain
Research Site
Gothenburg, 413 45, Sweden
Research Site
Lund, 221 85, Sweden
Research Site
Stockholm, 171 76, Sweden
Research Site
Changhua, 500, Taiwan
Research Site
Hsinchu, 300, Taiwan
Research Site
Kaohsiung City, 81362, Taiwan
Research Site
Kaohsiung City, 82445, Taiwan
Research Site
Kaohsiung City, 83301, Taiwan
Research Site
Taichung, 40447, Taiwan
Research Site
Taichung, 40705, Taiwan
Research Site
Tainan, 704, Taiwan
Research Site
Taipei, 10002, Taiwan
Research Site
Taipei, 112, Taiwan
Research Site
Taoyuan District, 333, Taiwan
Research Site
Aberdeen, AB2 2ZB, United Kingdom
Research Site
Bristol, BS2 8ED, United Kingdom
Research Site
Edinburgh, EH4 2XU, United Kingdom
Research Site
Glasgow, G12 0YN, United Kingdom
Research Site
Huddersfield, HD3 3EA, United Kingdom
Research Site
London, SW10 9NH, United Kingdom
Research Site
London, W1G 6AD, United Kingdom
Research Site
Manchester, M20 4BX, United Kingdom
Research Site
Newcastle upon Tyne, NE7 7DN, United Kingdom
Research Site
Nottingham, NG5 1PB, United Kingdom
Research Site
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (11)
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.
PMID: 41166679DERIVEDMurat-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.
PMID: 40311309DERIVEDKing-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.
PMID: 35575012DERIVEDSingh 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.
PMID: 35379563DERIVEDPapadimitrakopoulou 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.
PMID: 32861806DERIVEDPapadimitrakopoulou 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.
PMID: 31769875DERIVEDWu 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.
PMID: 30059262DERIVEDLee 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.
PMID: 29733770DERIVEDAkamatsu 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.
PMID: 29697876DERIVEDMok 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.
PMID: 27959700DERIVEDSoria 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.
PMID: 26159065DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- PRINCIPAL INVESTIGATOR
Yilong Wu, MD
Guangdong General Hospital, Guangdong, 510030, China
- PRINCIPAL INVESTIGATOR
Vassiliki A Papadimitrakopoulou, MD
The University of Texas/M.D. Anderson Cancer Center, Houston, Tx, USA
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 15, 2014
First Posted
June 2, 2014
Study Start
August 4, 2014
Primary Completion
April 15, 2016
Study Completion
December 15, 2023
Last Updated
January 7, 2025
Results First Posted
July 21, 2017
Record last verified: 2024-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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.