NCT02474355

Brief 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) therapy.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
3,017

participants targeted

Target at P75+ for phase_3 lung-cancer

Timeline
Completed

Started Sep 2015

Geographic Reach
15 countries

197 active sites

Status
completed

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 27, 2015

Completed
21 days until next milestone

First Posted

Study publicly available on registry

June 17, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

September 18, 2015

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 18, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 18, 2019

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

October 25, 2021

Completed
Last Updated

November 11, 2021

Status Verified

November 1, 2021

Enrollment Period

3.6 years

First QC Date

May 27, 2015

Results QC Date

August 12, 2021

Last Update Submit

November 10, 2021

Conditions

Keywords

NSCLCEGFRmT790M

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    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

    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)

    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)

    From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months]

Study Arms (1)

AZD9291

EXPERIMENTAL

Single arm of AZD9291, starting dose of 80mg

Procedure: T790M+ TestingProcedure: Baseline Visit Blood & Urine TestingProcedure: Baseline ECGProcedure: Visual Slit-Lamp TestingDrug: AZD9291 Dosing

Interventions

If a previous lab report is unavailable, the patient will need to have T790M+ testing.

AZD9291

Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria

AZD9291
Baseline ECGPROCEDURE

ECG to ensure absence of any cardiac abnormality

AZD9291

Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms

AZD9291

Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)

AZD9291

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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

You may not qualify if:

  • 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:
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (201)

Research Site

Buenos Aires, C1025ABI, Argentina

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Buenos Aires, C1431FWO, Argentina

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CABA, C1426ANZ, Argentina

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Bedford Park, 5042, Australia

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East Melbourne, 3002, Australia

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Kurralta Park, 5037, Australia

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Randwick, 2031, Australia

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Waratah, 2298, Australia

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Innsbruck, 6020, Austria

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Linz, 4020, Austria

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Salzburg, 5020, Austria

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Vienna, 1140, Austria

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Charleroi, 6000, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Barretos, 14784-400, Brazil

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Belo Horizonte, 30380-472, Brazil

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Florianópolis, 88034-000, Brazil

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Ijuí, 98700-000, Brazil

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Itajaí, 88310-110, Brazil

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Porto Alegre, 90035-903, Brazil

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Porto Alegre, 90610-000, Brazil

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Rio de Janeiro, 20231-050, Brazil

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Rio de Janeiro, 22793-080, Brazil

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Salvador, 40170-110, Brazil

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Salvador, 41950-640, Brazil

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São Paulo, 01221-020, Brazil

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São Paulo, 01246-000, Brazil

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São Paulo, 01509-900, Brazil

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Calgary, Alberta, T2N 4N2, Canada

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Burnaby, British Columbia, V5G 2X6, Canada

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Vancouver, British Columbia, V5Z 4E6, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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North York, Ontario, M2K 1E1, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Québec, Quebec, G1V 4G5, Canada

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Regina, Saskatchewan, S4T 7T1, Canada

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Beijing, 100020, China

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Beijing, 100021, China

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Beijing, 100044, China

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Beijing, 100048, China

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Beijing, 100053, China

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Beijing, 100071, China

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Beijing, 100142, China

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Beijing, 100730, China

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Beijing, 100853, China

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Beijing, 101149, China

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Changchun, 130012, China

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Changchun, 130021, China

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Changsha, 410003, China

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Chengdu, 610041, China

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Chongqing, 400037, China

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Chongqing, 400038, China

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Chongqing, 400042, China

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Dalian, 116011, China

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Fuzhou, 350009, China

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Fuzhou, 350014, China

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Fuzhou, 350025, China

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Guangzhou, 510080, China

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Guangzhou, 510120, China

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Guangzhou, 510515, China

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Haikou, 570311, China

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Hangzhou, 310003, China

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Hangzhou, 310006, China

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Hangzhou, 310009, China

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Hangzhou, 310022, China

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Harbin, 150049, China

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Hefei, 230001, China

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Hohhot, 010017, China

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Jinan, 2501117, China

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Kunming, 650118, China

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Linhai, 317000, China

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Nanchang, 330006, China

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Nanjing, 210002, China

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Nanjing, 210006, China

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Nanjing, 210008, China

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Nanjing, 210009, China

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Nanjing, 210029, China

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Nanning, 530021, China

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Nantong, 226361, China

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Qingdao, 266071, China

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Shanghai, 200025, China

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Shanghai, 200030, China

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Shanghai, 200032, China

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Shanghai, 200433, China

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Shenyang, 110001, China

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Shenyang, 110016, China

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Shenzhen, 518020, China

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Shijiahzhuang, 050011, China

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Tianjin, 300060, China

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Ürümqi, 830000, China

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Ürümqi, 830054, China

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Ürümqi, 831118, China

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Wuhan, 430022, China

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Wuhan, 430030, China

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Wuhan, 430071, China

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Wuhan, 430079, China

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Wuxi, 214062, China

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Xi'an, 710032, China

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Xi'an, 710061, China

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Yancheng, 224005, China

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Yangzhou, 225001, China

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Yantai, 264000, China

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Zhengzhou, 450008, China

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Vejle, 7100, Denmark

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Dublin, DUBLIN 4, Ireland

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Ancona, 60010, Italy

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Avellino, 83100, Italy

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Bari, 70124, Italy

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Bologna, 40138, Italy

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Brescia, 25100, Italy

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Cagliari, 09121, Italy

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Catania, 95123, Italy

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Florence, 50141, Italy

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Genova, 16132, Italy

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Lecce, 73100, Italy

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Livorno, 57124, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Novara, 28100, Italy

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Palermo, 90146, Italy

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Parma, 43126, Italy

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Perugia, 06132, Italy

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Pisa, 56124, Italy

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Reggio Emilia, 42100, Italy

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Roma, 00144, Italy

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Roma, 00152, Italy

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Roma, 00189, Italy

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Udine, 33100, Italy

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Verona, 37126, Italy

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Dammam, 31444, Saudi Arabia

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Riyadh, 11426, Saudi Arabia

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Anyang, 14068, South Korea

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Busan, 47392, South Korea

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Busan, 49241, South Korea

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Busan, 49267, South Korea

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Cheongju-si, 28644, South Korea

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Daegu, 41944, South Korea

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Daegu, 42415, South Korea

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Daejeon, 35015, South Korea

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Gangneung-si, 25440, South Korea

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Goyang-si, 10408, South Korea

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Incheon, 21565, South Korea

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Jeonju, 54907, South Korea

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Jeonnam, 58128, South Korea

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JinJoo, 52727, South Korea

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Seogu, 49201, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 01812, South Korea

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Seoul, 03080, South Korea

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Seoul, 03181, South Korea

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Seoul, 03722, South Korea

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Seoul, 05030, South Korea

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Seoul, 05355, South Korea

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Seoul, 05368, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Seoul, 07345, South Korea

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Seoul, 08308, South Korea

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Seoul, 156-707, South Korea

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Suwon, 16499, South Korea

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Ulsan, 44033, South Korea

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A Coruña, 15006, Spain

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Alicante, 03010, Spain

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Badalona, 08916, Spain

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Barcelona, 08036, Spain

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Castellon, 12002, Spain

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Donostia / San Sebastian, 20014, Spain

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Jaén, 23007, Spain

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Las Palmas de Gran Canaria, 35016, Spain

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León, 24071, Spain

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Madrid, 28007, Spain

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Madrid, 28040, Spain

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Majadahonda, 28222, Spain

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Oviedo, 33011, Spain

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Palma de Mallorca, 07010, Spain

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Seville, 41071, Spain

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Valencia, 46010, Spain

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Valencia, 46026, Spain

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Zaragoza, 50009, Spain

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Örebro, 70185, Sweden

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Uppsala, 751 85, Sweden

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Kaohsiung City, 807, Taiwan

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Kaohsiung City, 833, Taiwan

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Taichung, 00407, Taiwan

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Tainan, 704, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 11217, Taiwan

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Taipei, 11259, Taiwan

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Taoyuan District, 333, Taiwan

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Antrim, BT41 2RL, United Kingdom

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London, NW3 2QG, United Kingdom

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London, SW17 0QT, United Kingdom

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Norwich, NR4 7TY, United Kingdom

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Poole, BH15 2JB, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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Related Publications (3)

  • 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.

  • Cheema 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.

  • Leighl 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.

Related Links

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Limitations and Caveats

Participants alive at the time of national reimbursement or site closure were no longer followed for survival and therefore prematurely censored for the OS, PFS, and TTD analysis, leading to less mature data. As the timing of reimbursement and study closure differed between countries, duration of follow-up between sites and countries differed.

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca Clinical study Information Center

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2015

First Posted

June 17, 2015

Study Start

September 18, 2015

Primary Completion

April 18, 2019

Study Completion

April 18, 2019

Last Updated

November 11, 2021

Results First Posted

October 25, 2021

Record last verified: 2021-11

Locations