Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung CancerPhase 3FLAURANCT02296125
AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
A Phase 3 study testing Erlotinib 150/100 mg and Gefitinib 250 mg in people with Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer, run by AstraZeneca at 170 sites in 30 countries.
Trial summary
To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
- What is being tested?
- Erlotinib 150/100 mg and Gefitinib 250 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 674 participants
- Where
- 170 sitesin 30 countries
- Study dates
- 3 Dec 2014to 20 Nov 2025
- Phase
- Phase 3
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, aged at least 18 years.
- Pathologically confirmed adenocarcinoma of the lung.
- Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
- The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
- Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
- Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents).
- Provision of informed consent prior to any study specific procedures, sampling, and analysis.
- World Health Organization Performance Status of 0 to 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks
Who cannot join
- Treatment with any of the following:
- Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.
- Prior treatment with an EGFR-TKI.
- Major surgery within 4 weeks of the first dose of study drug.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
- Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
Show all 18Show fewer
- Alternative anti-cancer treatment
- Treatment with an investigational drug within five half-lives of the compound or any of its related material.
- Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
- Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
- Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
- Involvement in the planning and/or conduct of the study
Trial locations and contacts
170 sites in 30 countries.
170 sites in 30 countries
China20 sites
Research Site
Beijing, 100071
Research Site
Beijing, 100853
Research Site
Changchun, 130012
Research Site
Changchun, 130021
Research Site
Chongqing, 400037
Research Site
Chongqing, 400038
Research Site
Chongqing, 400042
Research Site
Fuzhou, 350025
Research Site
Guangzhou, 510080
Research Site
Hangzhou, 310022
Research Site
Nanjing, 210029
Research Site
Nanning, 530021
Research Site
Shanghai, 200433
Research Site
Shenyang, 110001
Research Site
Suzhou, 215006
Research Site
Ürümqi, 830000
Research Site
Wuhan, 430071
Research Site
Xi'an, 710038
Research Site
Xi'an, 710061
Research Site
Yangzhou, 225001
Japan18 sites
Research Site
Chūōku, 104-0045
Research Site
Fukuoka, 812-8582
Research Site
Hirakata-shi, 573-1191
Research Site
Kanazawa, 920-8641
Research Site
Kashiwa, 277-8577
Research Site
Kobe, 650-0047
Research Site
Matsuyama, 791-0280
Research Site
Natori-shi, 981-1293
Research Site
Osaka, 541-8567
Research Site
Osakasayama-shi, 589-8511
Research Site
Sagamihara-shi, 252-0375
Research Site
Sakaishi, 591-8555
Research Site
Sendai, 980-0873
Research Site
Sunto-gun, 411-8777
Research Site
Yokohama, 232-0024
Research Site
Yokohama, 236-0051
Research Site
Yokohama, 240-8555
Research Site
Yokohama, 241-8515
United States14 sites
Research Site
Anaheim, California, 92801
Research Site
Atlanta, Georgia, 30318
Research Site
Atlanta, Georgia, 30322
Research Site
Bethesda, Maryland, 20817
Research Site
Boston, Massachusetts, 02215
Research Site
Burlington, Vermont, 05401
Research Site
Lebanon, New Hampshire, 03756
Research Site
Louisville, Kentucky, 40202
Research Site
Marietta, Georgia, 30060
Research Site
Minneapolis, Minnesota, 55407
Research Site
Salisbury, North Carolina, 28144
Research Site
Santa Rosa, California, 95403
Research Site
Tampa, Florida, 33612
Research Site
West Hills, California, 91307
Spain10 sites
Research Site
A Coruña, 15006
Research Site
Barcelona, 08041
Research Site
Barcelona, 08221
Research Site
Barcelona, 08907
Research Site
Lleida, 25198
Research Site
Lugo, 27003
Research Site
Madrid, 28040
Research Site
Málaga, 29010
Research Site
Seville, 41014
Research Site
Zaragoza, 50009
Germany9 sites
Research Site
Bad Berka, 99437
Research Site
Berlin, 13125
Research Site
Gauting, 82131
Research Site
Halle, 06120
Research Site
Heidelberg, 69126
Research Site
Karlsruhe, 76137
Research Site
Lübeck, 23538
Research Site
München, 81925
Research Site
Villingen-Schwenningen, 78052
Italy8 sites
Research Site
Cremona, 26100
Research Site
Lecce, 73100
Research Site
Lecco, 23900
Research Site
Orbassano, 10043
Research Site
Parma, 43126
Research Site
Roma, 00144
Research Site
Sondrio, 23100
Research Site
Terni, 05100
Australia7 sites
Research Site
Camperdown, 2050
Research Site
Chermside, 4032
Research Site
Clayton, 3168
Research Site
Heidelberg, 3084
Research Site
Kogarah, 2217
Research Site
Nedlands, 6009
Research Site
Woolloongabba, 4102
South Korea7 sites
Research Site
Cheongju-si, 28644
Research Site
Incheon, 405-760
Research Site
Seongnam-si, 13620
Research Site
Seoul, 02841
Research Site
Seoul, 03722
Research Site
Seoul, 06591
Research Site
Seoul, 5030
Canada6 sites
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Hamilton, Ontario, L8V 5C2
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 1X5
Research Site
Toronto, Ontario, M5G 2M9
France6 sites
Research Site
Caen, F-14033
Research Site
Créteil, 94010
Research Site
Lyon, 69373
Research Site
Nantes, 44202
Research Site
Toulon Naval, 83800
Research Site
Villejuif, 94805
Hungary6 sites
Research Site
Farkasgyepü, 8582
Research Site
Gyöngyös - Mátraháza, 3200
Research Site
Miskolc, 3529
Research Site
Székesfehérvár, 8000
Research Site
Tatabánya, 2800
Research Site
Zalaegerszeg, 8900
Poland5 sites
Research Site
Brzozoów, 36-200
Research Site
Otwock, 05-400
Research Site
Poznan, 60-569
Research Site
Szczecin, 70-891
Research Site
Warsaw, 02-781
Taiwan5 sites
Research Site
Kaohsiung City, 833
Research Site
Taichung, 402
Research Site
Tainan, 704
Research Site
Tainan, 73657
Research Site
Taoyuan City, 333
Thailand5 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Bangkok, 10700
Research Site
Hat Yai, 90110
Research Site
Muang, 50200
Israel4 sites
Research Site
Haifa, 31999
Research Site
Kfar Saba, 4428164
Research Site
Petah Tikva, 49100
Research Site
Tel Litwinsky, 52621
Portugal4 sites
Research Site
Amadora, 2720-276
Research Site
Lisbon, 1769-001
Research Site
Porto, 4200-072
Research Site
Vila Nova de Gaia, 4434-502
Ukraine4 sites
Research Site
Dnipro, 49102
Research Site
Kryvyi Rih, 50048
Research Site
Lviv, 79031
Research Site
Sumy, 40022
United Kingdom4 sites
Research Site
Edinburgh, EH4 2XU
Research Site
London, NW1 2BU
Research Site
Maidstone, ME16 9QQ
Research Site
Withington, M20 4BX
Belgium3 sites
Research Site
Leuven, 3000
Research Site
Liège, 4000
Research Site
Roeselare, 8800
Malaysia3 sites
Research Site
Kuala Lumpur, 59100
Research Site
Kuantan, 25100
Research Site
Kuching, 93586
Philippines3 sites
Research Site
Cebu, 6000
Research Site
Manila, 1000
Research Site
Quezon City, 1100
Romania3 sites
Research Site
Bucharest, 022328
Research Site
Bucharest, 050098
Research Site
Craiova, 200347
Russia3 sites
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197758
Research Site
Saint Petersburg, 198255
Switzerland3 sites
Research Site
Lucerne, 6000
Research Site
Winterthur, 8401
Research Site
Zurich, 8091
Turkey (Türkiye)3 sites
Research Site
Ankara, 6500
Research Site
Istanbul, 34069
Research Site
Izmir, 35100
Vietnam3 sites
Research Site
Hanoi, 100000
Research Site
Hanoi, 10000
Research Site
Ho Chi Minh City, 70000
About this study
Official title: A Phase III, Double-blind, Randomised Study to Assess the Safety and Efficacy of AZD9291 Versus a Standard of Care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer.
To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer
Read the detailed description
This is a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib [250 mg orally, once daily] or erlotinib [150 mg orally, once daily]) in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
- Conditions
- Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
- Being tested
- AZD9291 80 mg/40 mg + placebo, Placebo Erlotinib 150/100mg, Placebo Gefitinib 250 mg, Erlotinib 150/100 mg, Gefitinib 250 mg
- Keywords
- Advanced Non-Small Cell Lung Cancer; EGFRm+; AZD9291; TKI; Phase III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291 80 mg/40 mg + placeboDrug
The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Placebo Erlotinib 150/100mgDrug
Also called Placebo Tarceva 150/100 mg
The initial dose of Placebo Erlotinib 150 mg once daily can be reduced to Placebo 100 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Placebo Gefitinib 250 mgDrug
Also called Placebo Iressa 250 mg
The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Erlotinib 150/100 mgDrug
Also called Tarceva 150/100 mg
The initial dose of Erlotinib 150mg once daily can be reduced to 10 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
Gefitinib 250 mgDrug
Also called Iressa 250mg
The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment.
Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
Placebo AZD9291 80 mg/ 40 mgDrug
The initial dose of Placebo AZD9291 80 mg once daily can be reduced to Placebo AZD9291 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
| Study group | Role | What they receive |
|---|---|---|
| AZD9291+ placebo | Experimental | AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150mg or 100mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule. Receives: Drug: AZD9291 80 mg/40 mg + placebo; Drug: Placebo Erlotinib 150/100mg; Drug: Placebo Gefitinib 250 mg |
| Standard of Care + placebo AZD9291 | Active comparator | Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule.
Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291). Receives: Drug: Erlotinib 150/100 mg; Drug: Gefitinib 250 mg; Drug: Placebo AZD9291 80 mg/ 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression Free Survival (PFS) (Months)
Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.
Measured: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months
Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS.
Measured: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Secondary outcomes (11)
Objective Response Rate (ORR)
ORR was defined as the number (%) of participants with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. ORR was based on Investigator assessment.
Measured: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Duration of Response (DoR)
Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.
Measured: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.
Measured: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Depth of Response
The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
Measured: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Overall Survival (OS)- Number of Participants With an Event
Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
Measured: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)
Plasma Concentrations of AZD9291
To characterise the pharmacokinetics (PK) of osimertinib
Measured: Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Plasma Concentrations of Metabolites AZ5104
To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ5104.
Measured: Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Plasma Concentrations of Metabolite AZ7550
To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ7550.
Measured: Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire)
The CTSQ-16 was a 16-item questionnaire measuring 3 domains related to participant's satisfaction with cancer therapy: Expectations of therapy, Feelings about side effects, and Satisfaction with therapy. Scores ranged from 0 to 100 for each domain, with a higher score associated with the best outcome on each domain. The three domains of interest were separately analysed using an ANCOVA stratified by race (Asian versus Non-Asian) and mutation type (Ex19del versus L858R). The results of the analyses were presented in terms of mean together with standard deviation.
Measured: Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)
The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Measured: Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30)
The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Measured: Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2014 (estimated)
- Study start3 Dec 2014
- Primary completion19 Jun 2017
- Study completion20 Nov 2025
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 (15)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced or Metastatic EGFR Sensitising Mutation Positive 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 674 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
- NCT02296125
- Sponsor's protocol ID
- D5160C00007
- Other IDs
- U1111-1160-2242, 2014-002694-11, 2014
- Acronym
- FLAURA
- Status last verified
- Apr 2026
- First submitted
- 22 Oct 2014
- Last updated
- 21 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Markovets A, Merino Vega D, Abbosh C, Quinn K, Chang K, Wienke S, Hartmaier R, Barrett JC, Hodgson D. Variability of Circulating Tumor DNA Levels in Plasma Samples From Patients With Advanced Non-Small-Cell Lung Cancer in the Absence of Treatment. JCO Precis Oncol. 2025 Oct;9:e2500287. doi: 10.1200/PO-25-00287. Epub 2025 Oct 30.
PubMed 41166679Murat-Onana ML, Ramalingam SS, Janne PA, Gray JE, Ahn MJ, John T, Yatabe Y, Huang X, Rukazenkov Y, Javey M, Brown H, Li-Sucholeiki X. EGFR mutation testing across the osimertinib clinical program. Lung Cancer. 2025 Jun;204:108549. doi: 10.1016/j.lungcan.2025.108549. Epub 2025 Apr 18.
PubMed 40311309Gray JE, Markovets A, Reungwetwattana T, Majem M, Nogami N, Peled N, Lee JS, Cho BC, Chewaskulyong B, John T, Han JY, Sebastian M, Todd A, Rukazenkov Y, Barrett C, Chmielecki J, Lee SM, Ramalingam SS, Hartmaier R. Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3. J Thorac Oncol. 2024 Nov;19(11):1525-1538. doi: 10.1016/j.jtho.2024.07.008. Epub 2024 Jul 17.
PubMed 39029876Viray H, Piper-Vallillo AJ, Widick P, Academia E, Shea M, Rangachari D, VanderLaan PA, Kobayashi SS, Costa DB. A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice. Cancers (Basel). 2024 Mar 7;16(6):1079. doi: 10.3390/cancers16061079.
PubMed 38539415Johnson M, Serra Traynor C, Vishwanathan K, Overend P, Hartmaier R, Markovets A, Chmielecki J, Mugundu GM, Barrett JC, Tomkinson H, Ramalingam SS. Longitudinal Circulating Tumor DNA Modeling to Predict Disease Progression in First-Line Mutant Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer. Clin Pharmacol Ther. 2024 Feb;115(2):349-360. doi: 10.1002/cpt.3113. Epub 2023 Dec 21.
PubMed 38010260Gray JE, Ahn MJ, Oxnard GR, Shepherd FA, Imamura F, Cheng Y, Okamoto I, Cho BC, Lin MC, Wu YL, Majem M, Gautschi O, Boyer M, Bulusu KC, Markovets A, Barrett JC, Hodge R, McKeown A, Hartmaier RJ, Chmielecki J, Papadimitrakopoulou VA, Ramalingam SS. Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA. Clin Cancer Res. 2023 Sep 1;29(17):3340-3351. doi: 10.1158/1078-0432.CCR-22-3146.
PubMed 37379430Walding A, Skaltsa K, Casamayor M, Ryden A. Time to deterioration of patient-reported outcomes in non-small cell lung cancer: exploring different definitions. Qual Life Res. 2022 Aug;31(8):2535-2543. doi: 10.1007/s11136-022-03088-0. Epub 2022 Jan 31.
PubMed 35099678Cheng Y, He Y, Li W, Zhang HL, Zhou Q, Wang B, Liu C, Walding A, Saggese M, Huang X, Fan M, Wang J, Ramalingam SS. Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. Target Oncol. 2021 Mar;16(2):165-176. doi: 10.1007/s11523-021-00794-6. Epub 2021 Feb 5.
PubMed 33544337Leighl NB, Karaseva N, Nakagawa K, Cho BC, Gray JE, Hovey T, Walding A, Ryden A, Novello S. Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer. Eur J Cancer. 2020 Jan;125:49-57. doi: 10.1016/j.ejca.2019.11.006. Epub 2019 Dec 12.
PubMed 31838405Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. doi: 10.1056/NEJMoa1913662. Epub 2019 Nov 21.
PubMed 31751012Brown H, Vansteenkiste J, Nakagawa K, Cobo M, John T, Barker C, Kohlmann A, Todd A, Saggese M, Chmielecki J, Markovets A, Scott M, Ramalingam SS. Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA. J Thorac Oncol. 2020 Jan;15(1):138-143. doi: 10.1016/j.jtho.2019.09.009. Epub 2019 Oct 9.
PubMed 31605792Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, Pang YK, Cobo M, Kasahara K, Cheng Y, Nogami N, Cho EK, Su WC, Zhang G, Huang X, Li-Sucholeiki X, Lentrichia B, Dearden S, Jenkins S, Saggese M, Rukazenkov Y, Ramalingam SS. Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Nov 15;25(22):6644-6652. doi: 10.1158/1078-0432.CCR-19-1126. Epub 2019 Aug 22.
PubMed 31439584Planchard D, Boyer MJ, Lee JS, Dechaphunkul A, Cheema PK, Takahashi T, Gray JE, Tiseo M, Ramalingam SS, Todd A, McKeown A, Rukazenkov Y, Ohe Y. Postprogression Outcomes for Osimertinib versus Standard-of-Care EGFR-TKI in Patients with Previously Untreated EGFR-mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 1;25(7):2058-2063. doi: 10.1158/1078-0432.CCR-18-3325. Epub 2019 Jan 18.
PubMed 30659024Ohe Y, Imamura F, Nogami N, Okamoto I, Kurata T, Kato T, Sugawara S, Ramalingam SS, Uchida H, Hodge R, Vowler SL, Walding A, Nakagawa K. Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset. Jpn J Clin Oncol. 2019 Jan 1;49(1):29-36. doi: 10.1093/jjco/hyy179.
PubMed 30508196Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.
PubMed 29151359