Advanced Non Small Cell Lung CancerPhase 1/2AURANCT01802632
AZD9291 First Time In Patients Ascending Dose Study
A Phase 1/2 study testing AZD9291 in people with Advanced Non Small Cell Lung Cancer and Advanced (Inoperable) Non Small Cell Lung Cancer, run by AstraZeneca at 45 sites in 10 countries.
Trial summary
This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Non Small Cell Lung Cancer, Advanced (Inoperable) Non Small Cell Lung Cancer
- What is being tested?
- AZD9291
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 603 participants
- Where
- 45 sitesin 10 countries
- Study dates
- 4 Mar 2013to 11 Dec 2023
- Phase
- Phase 1/2
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
- Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
- Aged at least 18 years. Patients from Japan aged at least 20 years.
- Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC).
- Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib (with the exception of 1st line expansion cohort). In addition other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
- Patients (with the exception of 1st line expansion cohort) must fulfil one of the following:
- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR
Show all 14Show fewer
- Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI.
- Previous treatment with a single-agent EGFR TKI (e.g. gefitinib or erlotinib).
- Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing or evidence of non-child bearing potential.
- Male patients should be willing to use barrier contraception.
- For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
- For dose expansion and extension cohorts, patients must also have confirmation of tumour T790M mutation status (confirmed positive or negative) from a biopsy sample taken after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy).
- Prior to entry a result from the central analysis of the patient's T790M mutation status must be obtained.
- World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
Who cannot join
- Treatment with an EGFR TKI (erlotinib or gefitinib) within 8 days (approximately 5x half-life) of the first dose of study treatment.
- Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
- AZD9291 in the present study (ie, dosing with AZD9291 previously initiated in this study).
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection.
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
Trial locations and contacts
45 sites in 10 countries.
45 sites in 10 countries
Japan15 sites
Research Site
Chiba, 260-8717
Research Site
Fukuoka, 811-1395
Research Site
Fukuoka, 812-8582
Research Site
Habikino-shi, 583-8588
Research Site
Hirakata-shi, 573-1191
Research Site
Hiroshima, 730-8518
Research Site
Kanazawa, 920-8641
Research Site
Kashiwa, 227-8577
Research Site
Kobe, 650-0047
Research Site
Matsuyama, 790-0007
Research Site
Okayama, 700-8558
Research Site
Shinjuku-ku, 160-0023
Research Site
Sunto-gun, 411-8777
Research Site
Takatsuki-shi, 569-8686
Research Site
Yokohama, 221-0855
United States7 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Aurora, Colorado, 80045
Research Site
Boston, Massachusetts, 02114
Research Site
Boston, Massachusetts, 02215
Research Site
Charlotte, North Carolina, 28204
Research Site
Houston, Texas, 77030
Research Site
Nashville, Tennessee, 37232
South Korea4 sites
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 6351
Australia3 sites
Research Site
Heidelberg, 3084
Research Site
Kogarah, 2217
Research Site
Nedlands, 6009
France3 sites
Research Site
Pierre-Bénite, 69310
Research Site
Saint-Herblain, 44805
Research Site
Villejuif, 94800
Germany3 sites
Research Site
Cologne, 50924
Research Site
Essen, 45122
Research Site
Würzburg, 97080
Italy3 sites
Research Site
Genova, 16100
Research Site
Orbassano, 10043
Research Site
Roma, 00144
Spain3 sites
Research Site
Madrid, 08035
Research Site
Madrid, 28041
Research Site
Seville, 41013
United Kingdom2 sites
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN
About this study
Official title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AZD9291 in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.
Read the detailed description
A Phase I/II, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Ascending Doses of AZD9291 in Patients with Advanced Non Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent (AURA)
- Being tested
- AZD9291
- Keywords
- Oncology,, Non Small Cell Lung Cancer,, Metastatic,, EGFR sensitivity mutation,, T790M resistance mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291Drug
Starting dose 20 mg, administered once daily. If tolerated subsequent cohorts will test increasing doses of AZD9291, until a maximum tolerated dose or maximum feasible dose is defined
| Study group | Role | What they receive |
|---|---|---|
| Daily dose of AZD9291 | Experimental | Daily oral dose of AZD9291 Receives: Drug: AZD9291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) for Dose Expansion Population
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 (by investigator assessment) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
Best Objective Response (BOR) for Dose Escalation Population
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. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)
Objective Response Rate (ORR) for Extension Population
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 (by independent central review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)
Secondary outcomes (3)
Duration of Response (DoR) for Dose Expansion Population
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 was defined as the time from the date of first documented response (CR or PR that was subsequently confirmed) until the date of documented progression (PD) or death in the absence of disease progression (by investigator assessment).
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
Progression-Free Survival (PFS) for Dose Expansion Population
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 first dose until the date of PD (by independent central review) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from AZD9291 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 approximately 21 months (at time of analysis)
Best Objective Response (BOR) for 80mg AZD9291 Extension Population
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. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.
Measured: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2013 (estimated)
- Study start4 Mar 2013
- Primary completion1 May 2015
- Study completion11 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 (16)Papers the sponsor has linked to this study.
- Other trials for Advanced 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 603 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yuri Rukazenkov, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01802632
- Sponsor's protocol ID
- D5160C00001
- Other IDs
- 2012-004628-39
- Acronym
- AURA
- Status last verified
- Apr 2026
- First submitted
- 25 Feb 2013
- Last updated
- 20 Apr 2026
- 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Murat-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 40311309Martin ML, Correll J, Walding A, Ryden A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.
PubMed 34056687Ahn MJ, Han JY, Kim DW, Cho BC, Kang JH, Kim SW, Yang JC, Mitsudomi T, Lee JS. Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies. Cancer Res Treat. 2020 Jan;52(1):284-291. doi: 10.4143/crt.2019.200. Epub 2019 Jul 23.
PubMed 31345012Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.
PubMed 30512189Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Janne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018 Nov 1;4(11):1527-1534. doi: 10.1001/jamaoncol.2018.2969.
PubMed 30073261Kiura K, Yoh K, Katakami N, Nogami N, Kasahara K, Takahashi T, Okamoto I, Cantarini M, Hodge R, Uchida H. Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples. Cancer Sci. 2018 Apr;109(4):1177-1184. doi: 10.1111/cas.13511. Epub 2018 Feb 27.
PubMed 29363250Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.
PubMed 29293889Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Janne PA. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Mar 20;36(9):841-849. doi: 10.1200/JCO.2017.74.7576. Epub 2017 Aug 25.
PubMed 28841389Thress KS, Jacobs V, Angell HK, Yang JC, Sequist LV, Blackhall F, Su WC, Schuler M, Wolf J, Gold KA, Cantarini M, Barrett JC, Janne PA. Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial. J Thorac Oncol. 2017 Oct;12(10):1588-1594. doi: 10.1016/j.jtho.2017.07.011. Epub 2017 Jul 24.
PubMed 28751247Dearden S, Brown H, Jenkins S, Thress KS, Cantarini M, Cole R, Ranson M, Janne PA. EGFR T790M mutation testing within the osimertinib AURA Phase I study. Lung Cancer. 2017 Jul;109:9-13. doi: 10.1016/j.lungcan.2017.04.011. Epub 2017 Apr 19.
PubMed 28577957Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, Pickup K, Jordan A, Hickey M, Grist M, Box M, Johnstrom P, Varnas K, Malmquist J, Thress KS, Janne PA, Cross D. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res. 2016 Oct 15;22(20):5130-5140. doi: 10.1158/1078-0432.CCR-16-0399. Epub 2016 Jul 19.
PubMed 27435396Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Janne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Oct 1;34(28):3375-82. doi: 10.1200/JCO.2016.66.7162. Epub 2016 Jun 27.
PubMed 27354477Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, Hammett T, Cantarini M, Barrett JC. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015 Dec;90(3):509-15. doi: 10.1016/j.lungcan.2015.10.004. Epub 2015 Oct 9.
PubMed 26494259Kim TM, Song A, Kim DW, Kim S, Ahn YO, Keam B, Jeon YK, Lee SH, Chung DH, Heo DS. Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor. J Thorac Oncol. 2015 Dec;10(12):1736-44. doi: 10.1097/JTO.0000000000000688.
PubMed 26473643Yu HA, Tian SK, Drilon AE, Borsu L, Riely GJ, Arcila ME, Ladanyi M. Acquired Resistance of EGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor: Emergence of a Third Mutation (C797S) in the EGFR Tyrosine Kinase Domain. JAMA Oncol. 2015 Oct;1(7):982-4. doi: 10.1001/jamaoncol.2015.1066. No abstract available.
PubMed 26181354