Lung CancerPhase 3ASTRISNCT02474355
Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC
A Phase 3 study testing T790M+ Testing, Baseline Visit Blood & Urine Testing and Baseline ECG in people with Lung Cancer, run by AstraZeneca at 201 sites in 16 countries.
Trial summary
The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI)… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Lung Cancer
- What is being tested?
- T790M+ Testing, Baseline Visit Blood & Urine Testing and Baseline ECG
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,017 participants
- Where
- 201 sitesin 16 countries
- Study dates
- 18 Sep 2015to 18 Apr 2019
- 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
- Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures
- Adults (according to each country regulations for age of majority)
- Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation
- Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment
- World Health Organization (WHO) performance status 0-2
- Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline (please refer to IB for guidance)
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- ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6
- Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential
- Male patients must be willing to use barrier contraception, i.e., condoms
Who cannot join
- Previous (within 6 months) or current treatment with AZD9291
- Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.
- Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration;
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
- Any of the following cardiac criteria:
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- Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
- Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment
- History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291
Trial locations and contacts
201 sites in 16 countries.
201 sites in 16 countries
China67 sites
Research Site
Beijing, 100020
Research Site
Beijing, 100021
Research Site
Beijing, 100044
Research Site
Beijing, 100048
Research Site
Beijing, 100053
Research Site
Beijing, 100071
Research Site
Beijing, 100142
Research Site
Beijing, 100730
Research Site
Beijing, 100853
Research Site
Beijing, 101149
Research Site
Changchun, 130012
Research Site
Changchun, 130021
Research Site
Changsha, 410003
Research Site
Chengdu, 610041
Research Site
Chongqing, 400037
Research Site
Chongqing, 400038
Research Site
Chongqing, 400042
Research Site
Dalian, 116011
Research Site
Fuzhou, 350009
Research Site
Fuzhou, 350014
Research Site
Fuzhou, 350025
Research Site
Guangzhou, 510080
Research Site
Guangzhou, 510120
Research Site
Guangzhou, 510515
Research Site
Haikou, 570311
Research Site
Hangzhou, 310003
Research Site
Hangzhou, 310006
Research Site
Hangzhou, 310009
Research Site
Hangzhou, 310022
Research Site
Harbin, 150049
Research Site
Hefei, 230001
Research Site
Hohhot, 010017
Research Site
Jinan, 2501117
Research Site
Kunming, 650118
Research Site
Linhai, 317000
Research Site
Nanchang, 330006
Research Site
Nanjing, 210002
Research Site
Nanjing, 210006
Research Site
Nanjing, 210008
Research Site
Nanjing, 210009
Research Site
Nanjing, 210029
Research Site
Nanning, 530021
Research Site
Nantong, 226361
Research Site
Qingdao, 266071
Research Site
Shanghai, 200025
Research Site
Shanghai, 200030
Research Site
Shanghai, 200032
Research Site
Shanghai, 200433
Research Site
Shenyang, 110001
Research Site
Shenyang, 110016
Research Site
Shenzhen, 518020
Research Site
Shijiahzhuang, 050011
Research Site
Tianjin, 300060
Research Site
Ürümqi, 830000
Research Site
Ürümqi, 830054
Research Site
Ürümqi, 831118
Research Site
Wuhan, 430022
Research Site
Wuhan, 430030
Research Site
Wuhan, 430071
Research Site
Wuhan, 430079
Research Site
Wuxi, 214062
Research Site
Xi'an, 710032
Research Site
Xi'an, 710061
Research Site
Yancheng, 224005
Research Site
Yangzhou, 225001
Research Site
Yantai, 264000
Research Site
Zhengzhou, 450008
South Korea31 sites
Research Site
Anyang, 14068
Research Site
Busan, 47392
Research Site
Busan, 49241
Research Site
Busan, 49267
Research Site
Cheongju-si, 28644
Research Site
Daegu, 41944
Research Site
Daegu, 42415
Research Site
Daejeon, 35015
Research Site
Gangneung-si, 25440
Research Site
Goyang-si, 10408
Research Site
Incheon, 21565
Research Site
Jeonju, 54907
Research Site
Jeonnam, 58128
Research Site
JinJoo, 52727
Research Site
Seogu, 49201
Research Site
Seongnam-si, 13620
Research Site
Seoul, 01812
Research Site
Seoul, 03080
Research Site
Seoul, 03181
Research Site
Seoul, 03722
Research Site
Seoul, 05030
Research Site
Seoul, 05355
Research Site
Seoul, 05368
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Research Site
Seoul, 07345
Research Site
Seoul, 08308
Research Site
Seoul, 156-707
Research Site
Suwon, 16499
Research Site
Ulsan, 44033
Italy24 sites
Research Site
Ancona, 60010
Research Site
Avellino, 83100
Research Site
Bari, 70124
Research Site
Bologna, 40138
Research Site
Brescia, 25100
Research Site
Cagliari, 09121
Research Site
Catania, 95123
Research Site
Florence, 50141
Research Site
Genova, 16132
Research Site
Lecce, 73100
Research Site
Livorno, 57124
Research Site
Milan, 20141
Research Site
Naples, 80131
Research Site
Novara, 28100
Research Site
Palermo, 90146
Research Site
Parma, 43126
Research Site
Perugia, 06132
Research Site
Pisa, 56124
Research Site
Reggio Emilia, 42100
Research Site
Roma, 00144
Research Site
Roma, 00152
Research Site
Roma, 00189
Research Site
Udine, 33100
Research Site
Verona, 37126
Spain18 sites
Research Site
A Coruña, 15006
Research Site
Alicante, 03010
Research Site
Badalona, 08916
Research Site
Barcelona, 08036
Research Site
Castellon, 12002
Research Site
Donostia / San Sebastian, 20014
Research Site
Jaén, 23007
Research Site
Las Palmas de Gran Canaria, 35016
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León, 24071
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Madrid, 28007
Research Site
Madrid, 28040
Research Site
Majadahonda, 28222
Research Site
Oviedo, 33011
Research Site
Palma de Mallorca, 07010
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Seville, 41071
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Valencia, 46010
Research Site
Valencia, 46026
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Zaragoza, 50009
Brazil14 sites
Research Site
Barretos, 14784-400
Research Site
Belo Horizonte, 30380-472
Research Site
Florianópolis, 88034-000
Research Site
Ijuí, 98700-000
Research Site
Itajaí, 88310-110
Research Site
Porto Alegre, 90035-903
Research Site
Porto Alegre, 90610-000
Research Site
Rio de Janeiro, 20231-050
Research Site
Rio de Janeiro, 22793-080
Research Site
Salvador, 40170-110
Research Site
Salvador, 41950-640
Research Site
São Paulo, 01221-020
Research Site
São Paulo, 01246-000
Research Site
São Paulo, 01509-900
Canada12 sites
Research Site
Burnaby, British Columbia, V5G 2X6
Research Site
Calgary, Alberta, T2N 4N2
Research Site
Hamilton, Ontario, L8V 5C2
Research Site
Montreal, Quebec, H4A 3J1
Research Site
North York, Ontario, M2K 1E1
Research Site
Oshawa, Ontario, L1G 2B9
Research Site
Québec, Quebec, G1V 4G5
Research Site
Regina, Saskatchewan, S4T 7T1
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Toronto, Ontario, M4N 3M5
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Toronto, Ontario, M5G 1X5
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 4E6
Taiwan8 sites
Research Site
Kaohsiung City, 807
Research Site
Kaohsiung City, 833
Research Site
Taichung, 00407
Research Site
Tainan, 704
Research Site
Taipei, 10002
Research Site
Taipei, 11217
Research Site
Taipei, 11259
Research Site
Taoyuan, 333
United Kingdom6 sites
Research Site
Antrim, BT41 2RL
Research Site
London, NW3 2QG
Research Site
London, SW17 0QT
Research Site
Norwich, NR4 7TY
Research Site
Poole, BH15 2JB
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Wolverhampton, WV10 0QP
Australia5 sites
Research Site
Bedford Park, 5042
Research Site
East Melbourne, 3002
Research Site
Kurralta Park, 5037
Research Site
Randwick, 2031
Research Site
Waratah, 2298
Austria4 sites
Research Site
Innsbruck, 6020
Research Site
Linz, 4020
Research Site
Salzburg, 5020
Research Site
Vienna, 1140
Argentina3 sites
Research Site
Buenos Aires, C1025ABI
Research Site
Buenos Aires, C1431FWO
Research Site
CABA, C1426ANZ
Belgium3 sites
Research Site
Charleroi, 6000
Research Site
Edegem, 2650
Research Site
Leuven, 3000
Saudi Arabia2 sites
Research Site
Dammam, 31444
Research Site
Riyadh, 11426
About this study
Official title: Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)
The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Read the detailed description
Objective: The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Study site(s) and number of patients planned: Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world (America, Asia).
Study Design This will be an open-label, single-arm, multinational, multicenter, real world treatment study.
Target patient population: Adult patients (fulfilling the definition of "age of majority" per local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC with confirmed T790M mutation, who have received prior EGFR-TKI therapy.
Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent, selective, irreversible inhibitor of both EGFR-TKI sensitising and resistance mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered orally as one 80 mg tablet once a day.
Duration of IP administration: Patients may continue to receive AZD9291 as long as they continue to show clinical benefit, as judged by the investigator, and in the absence of discontinuation criteria). The study will be closed in each participating country as soon as possible following national reimbursement of AZD9291 in that country (up to a max of 90 days post reimbursement). Enrolment will be closed within 6 months after market license approval in that country or at national reimbursement, whichever is sooner. Patients withdrawing from the treatment prior to national reimbursement will be followed up as part of this study. Patients on treatment will receive commercial supply until documented disease progression as per investigator assessment.
In the event that national reimbursement should not be granted following a reasonable time after market license approval in the country, the study will be closed in a maximum period of 18 months after the last patient is enrolled in that country. If applicable, timelines for conversion to commercial drug will be agreed with local bodies which may include regulatory agencies, ethics committees, and institutions. Patient will be followed until death or lost to follow-up.
Study measures: Data collected will include patient demographics, information needed to determine patient eligibility (including medical history, past and current disease characteristics, and tumor EGFR mutational status), AZD9291 exposure, investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), and safety (including serious adverse events [SAEs], adverse events leading to dose modification, and adverse events of special interest [interstitial lung disease/pneumonitis-like events, and QTc prolongation events]).
Statistical methods: All data will be presented for the overall full analysis/evaluable set, and also by cohorts defined by number and type of previous treatment lines for the advanced disease. Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be summarised by the number of observations, mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarised by frequency counts and percentages for each category. OS and PFS will be summarized using Kaplan-Meier estimates of the median time to death or censoring and quartiles together with their 95% confidence intervals.
- Conditions
- Lung Cancer
- Being tested
- T790M+ Testing, Baseline Visit Blood & Urine Testing, Baseline ECG, Visual Slit-Lamp Testing, AZD9291 Dosing
- Keywords
- NSCLC, EGFRm, T790M
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T790M+ TestingProcedure or surgery
If a previous lab report is unavailable, the patient will need to have T790M+ testing.
Baseline Visit Blood & Urine TestingProcedure or surgery
Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria
Baseline ECGProcedure or surgery
ECG to ensure absence of any cardiac abnormality
Visual Slit-Lamp TestingProcedure or surgery
Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms
AZD9291 DosingDrug
Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)
| Study group | Role | What they receive |
|---|---|---|
| AZD9291 | Experimental | Single arm of AZD9291, starting dose of 80mg Receives: Procedure: T790M+ Testing; Procedure: Baseline Visit Blood & Urine Testing; Procedure: Baseline ECG; Procedure: Visual Slit-Lamp Testing; Drug: AZD9291 Dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS was defined as the time, in months from the date of first dose of Osimertinib until death due to any cause, or at last documented contact with participant status "alive" (in this study any participants alive at study discontinuation, or lost to follow-up was considered being censored at study discontinuation date or at the last known date participant was alive). OS was summarized using a Kaplan-Meier (KM) estimate of the median time to death or censoring together with their 95% confidence intervals.
Measured: From the date of first dose of Osimertinib until the date of death (due to any cause) or last participant contact [up to 43 months]
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety assessment of Osimertinib was analyzed by evaluating AEs and SAEs.
Measured: From screening to progression follow-up [every 6 weeks +/- 1 week] relative to the date of enrolment until the end of study [up to 43 months]
Secondary outcomes (3)
Progression Free Survival
PFS was defined as the time, in months from first dose of AZD9291/ost/study drug/ study treatment until the date of disease progression or death in the absence of progression. Participants who had not progressed or died at study discontinuation were censored at the time of the latest date of disease assessment. PFS was summarized using KM estimates of the median time to progression or death with their 95% confidence intervals.
Measured: From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Time to Treatment Discontinuation (TTD)
TTD or death was assessed as a supportive summary to PFS and defined as the time from the date of the first dose of osimertinib in the study until the date of osimertinib discontinuation or death, regardless of the reason for discontinuation. TTD was summarized using KM estimates of the median times to progression or death or treatment discontinuation.
Measured: From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Response Rate (RR)
RR was defined as the number (%) of participants with a best response (by Investigator assessment) of 'responding', regardless of the method of evaluation, and was based on a subset of the full analysis set consisting of subjects with at least one documented response assessment. RR was summarised together with the 95% CI.
Measured: From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2015 (estimated)
- Study start18 Sep 2015
- Primary completion18 Apr 2019
- Study completion18 Apr 2019
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 (3)Papers the sponsor has linked to this study.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3,017 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02474355
- Sponsor's protocol ID
- D5160C00022
- Acronym
- ASTRIS
- Status last verified
- Nov 2021
- First submitted
- 27 May 2015
- Last updated
- 11 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zhou Q, Zhang HL, Jiang LY, Shi YK, Chen Y, Yu JM, Zhou CC, He Y, Hu YP, Liang ZA, Pan YY, Zhuo WL, Song Y, Wu G, Chen GY, Lu Y, Zhang CY, Zhang YP, Cheng Y, Lu S, Wang CL, Zhou JY, Liu YP, He JX, Wang J, Wu YL. Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study. J Cancer Res Clin Oncol. 2023 Sep;149(12):10771-10780. doi: 10.1007/s00432-023-04923-8. Epub 2023 Jun 14.
PubMed 37316692Cheema P, Cho BC, Freitas H, Provencio M, Chen YM, Kim SW, Wu YL, Passaro A, Martin C, Tiseo M, Chang GC, Park K, Solomon B, Burghuber O, Laskin J, Wang Z, Lee SY, Hu Y, Vansteenkiste J, Zhang HL, Hanrahan E, Geldart T, Taylor R, Servidio L, Li J, Marinis F. A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data. Future Oncol. 2023 Jan;19(1):61-75. doi: 10.2217/fon-2022-0919. Epub 2023 Jan 19.
PubMed 36656302Leighl NB, Kamel-Reid S, Cheema PK, Laskin J, Karsan A, Zhang T, Stockley T, Barnes TA, Tudor RA, Liu G, Owen S, Rothenstein J, Burkes RL, Iqbal M, Spatz A, van Kempen LC, Izevbaye I, Laurence D, Le LW, Tsao MS. Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories. JCO Precis Oncol. 2020 Nov;4:520-533. doi: 10.1200/PO.19.00335.
PubMed 35050743
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)
- ClinicalTrials.gov ID
- NCT02474355
- Acronym / sponsor ID
- ASTRIS / D5160C00022
- Conditions
- Lung Cancer
- Keywords
- NSCLC, EGFRm, T790M
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,017 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 18 Sep 2015 (actual)
- Primary completion
- 18 Apr 2019 (actual)
- Study completion
- 18 Apr 2019 (actual)
- First posted
- 17 Jun 2015 (estimated)
- Results
- Posted 25 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Detailed description
Objective: The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Study site(s) and number of patients planned: Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world (America, Asia).
Study Design This will be an open-label, single-arm, multinational, multicenter, real world treatment study.
Target patient population: Adult patients (fulfilling the definition of "age of majority" per local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC with confirmed T790M mutation, who have received prior EGFR-TKI therapy.
Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent, selective, irreversible inhibitor of both EGFR-TKI sensitising and resistance mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered orally as one 80 mg tablet once a day.
Duration of IP administration: Patients may continue to receive AZD9291 as long as they continue to show clinical benefit, as judged by the investigator, and in the absence of discontinuation criteria). The study will be closed in each participating country as soon as possible following national reimbursement of AZD9291 in that country (up to a max of 90 days post reimbursement). Enrolment will be closed within 6 months after market license approval in that country or at national reimbursement, whichever is sooner. Patients withdrawing from the treatment prior to national reimbursement will be followed up as part of this study. Patients on treatment will receive commercial supply until documented disease progression as per investigator assessment.
In the event that national reimbursement should not be granted following a reasonable time after market license approval in the country, the study will be closed in a maximum period of 18 months after the last patient is enrolled in that country. If applicable, timelines for conversion to commercial drug will be agreed with local bodies which may include regulatory agencies, ethics committees, and institutions. Patient will be followed until death or lost to follow-up.
Study measures: Data collected will include patient demographics, information needed to determine patient eligibility (including medical history, past and current disease characteristics, and tumor EGFR mutational status), AZD9291 exposure, investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), and safety (including serious adverse events [SAEs], adverse events leading to dose modification, and adverse events of special interest [interstitial lung disease/pneumonitis-like events, and QTc prolongation events]).
Statistical methods: All data will be presented for the overall full analysis/evaluable set, and also by cohorts defined by number and type of previous treatment lines for the advanced disease. Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be summarised by the number of observations, mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarised by frequency counts and percentages for each category. OS and PFS will be summarized using Kaplan-Meier estimates of the median time to death or censoring and quartiles together with their 95% confidence intervals.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD9291 | Experimental | Procedure: T790M+ Testing, Procedure: Baseline Visit Blood & Urine Testing, Procedure: Baseline ECG, Procedure: Visual Slit-Lamp Testing, Drug: AZD9291 DosingSingle arm of AZD9291, starting dose of 80mg |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures
- Adults (according to each country regulations for age of majority)
- Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation
- Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment
- World Health Organization (WHO) performance status 0-2
Key exclusion criteria (11 listed)
- Previous (within 6 months) or current treatment with AZD9291
- Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.
- Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration;
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
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 |
|---|---|---|
| T790M+ TestingIf a previous lab report is unavailable, the patient will need to have T790M+ testing. | Procedure or surgery | AZD9291 |
| Baseline Visit Blood & Urine TestingBlood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria | Procedure or surgery | AZD9291 |
| Baseline ECGECG to ensure absence of any cardiac abnormality | Procedure or surgery | AZD9291 |
| Visual Slit-Lamp TestingSlit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms | Procedure or surgery | AZD9291 |
| AZD9291 DosingPatients to be provided with AZD9291 every 6 weeks (+/- 7 days) | Drug | AZD9291 |
Primary outcome
Overall Survival (OS)
Time frame: From the date of first dose of Osimertinib until the date of death (due to any cause) or last participant contact [up to 43 months]
OS was defined as the time, in months from the date of first dose of Osimertinib until death due to any cause, or at last documented contact with participant status "alive" (in this study any participants alive at study discontinuation, or lost to follow-up was considered being censored at study discontinuation date or at the last known date participant was alive). OS was summarized using a Kaplan-Meier (KM) estimate of the median time to death or censoring together with their 95% confidence intervals.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From screening to progression follow-up [every 6 weeks +/- 1 week] relative to the date of enrolment until the end of study [up to 43 months]
Safety assessment of Osimertinib was analyzed by evaluating AEs and SAEs.
3 secondary outcomes
Progression Free Survival
Time frame: From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Time to Treatment Discontinuation (TTD)
Time frame: From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Response Rate (RR)
Time frame: From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37316692Zhou Q, Zhang HL, Jiang LY, Shi YK, Chen Y, Yu JM, Zhou CC, He Y, Hu YP, Liang ZA, Pan YY, Zhuo WL, Song Y, Wu G, Chen GY, Lu Y, Zhang CY, Zhang YP, Cheng Y, Lu S, Wang CL, Zhou JY, Liu YP, He JX, Wang J, Wu YL. Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study. J Cancer Res Clin Oncol. 2023 Sep;149(12):10771-10780. doi: 10.1007/s00432-023-04923-8. Epub 2023 Jun 14.
- Derived from this study: PubMed 36656302Cheema P, Cho BC, Freitas H, Provencio M, Chen YM, Kim SW, Wu YL, Passaro A, Martin C, Tiseo M, Chang GC, Park K, Solomon B, Burghuber O, Laskin J, Wang Z, Lee SY, Hu Y, Vansteenkiste J, Zhang HL, Hanrahan E, Geldart T, Taylor R, Servidio L, Li J, Marinis F. A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data. Future Oncol. 2023 Jan;19(1):61-75. doi: 10.2217/fon-2022-0919. Epub 2023 Jan 19.
- Derived from this study: PubMed 35050743Leighl NB, Kamel-Reid S, Cheema PK, Laskin J, Karsan A, Zhang T, Stockley T, Barnes TA, Tudor RA, Liu G, Owen S, Rothenstein J, Burkes RL, Iqbal M, Spatz A, van Kempen LC, Izevbaye I, Laurence D, Le LW, Tsao MS. Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories. JCO Precis Oncol. 2020 Nov;4:520-533. doi: 10.1200/PO.19.00335.
- D5160C00022 Clinical Study ProtocolLink provided by the sponsor.
- D5160C00022 Statistical Analysis PlanLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
201 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing T790M+ Testing, Baseline Visit Blood & Urine Testing and Baseline ECG in people with Lung Cancer, run by AstraZeneca at 201 sites in 16 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 9 inclusion and 11 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 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 201 sites in China, South Korea, Italy, Spain, Brazil and 11 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 25 Oct 2021). 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?
Overall Survival (OS) (time frame: From the date of first dose of Osimertinib until the date of death (due to any cause) or last participant contact [up to 43 months]). 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 NCT02474355, which also lists 3 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 11 Nov 2021.