Study Summary
This trial will test a new drug on patients with NSCLC who have already tried other treatments. They will look at side effects, how much of the drug is in the body, and how well it works against the cancer.
Eligible Conditions
- Non-Small Cell Lung Cancer
- Advanced Non Small Cell Lung Cancer
Treatment Effectiveness
Effectiveness Progress
Study Objectives
3 Primary · 3 Secondary · Reporting Duration: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)
Month 12
Best Objective Response (BOR) for 80mg AZD9291 Extension Population
Objective Response Rate (ORR) for Extension Population
Month 21
Duration of Response (DoR) for Dose Expansion Population
Objective Response Rate (ORR) for Dose Expansion Population
Progression-Free Survival (PFS) for Dose Expansion Population
Month 25
Best Objective Response (BOR) for Dose Escalation Population
Trial Safety
Safety Progress
Side Effects for
Selumetinib+Docetaxel With a Seq. Switch to a MEDI4736
100%Constipation
100%Diarrhoea
100%Dyspepsia
100%Vomiting
100%Myalgia
100%Rash
50%Hypokalaemia
50%Atrial fibrillation
50%Diverticulitis
50%Enterocolitis infectious
50%Anaemia
50%Mitral valve stenosis
50%Stomatitis
50%Chills
50%Dyspnoea
50%Pyrexia
50%Fatigue
50%Oedema peripheral
50%Dizziness
50%Headache
50%Thrombosis in device
50%Anxiety
50%Deep vein thrombosis
50%Hot flush
50%Hypertension
50%Hypotension
Trial Design
1 Treatment Group
Daily dose of AZD9291
1 of 1
Experimental Treatment
603 Total Participants · 1 Treatment Group
Primary Treatment: AZD9291 · No Placebo Group · Phase 1 & 2
Daily dose of AZD9291
Drug
Experimental Group · 1 Intervention: AZD9291 · Intervention Types: DrugTreatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Osimertinib
FDA approved
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: recist tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)
Who is running the clinical trial?
AstraZenecaLead Sponsor
4,021 Previous Clinical Trials
240,380,522 Total Patients Enrolled
Yuri RukazenkovStudy DirectorAstraZeneca
3 Previous Clinical Trials
30 Total Patients Enrolled
Eligibility Criteria
Age 18 - 130 · All Participants · 12 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:References
- Ramalingam, Suresh S., James C.-H. Yang, Chee Khoon Lee, Takayasu Kurata, Dong-Wan Kim, Thomas John, Naoyuki Nogami, et al.. 2018. “Osimertinib as First-line Treatment of egfr Mutation–positive Advanced Non–small-cell Lung Cancer”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2017.74.7576.
- Yu, Helena A., Shaozhou K. Tian, Alexander E. Drilon, Laetitia Borsu, Gregory J. Riely, Maria E. Arcila, and Marc Ladanyi. 2015. “Acquired Resistance Ofegfr-mutant Lung Cancer to a T790m-specific EGFR Inhibitor”. JAMA Oncology. American Medical Association (AMA). doi:10.1001/jamaoncol.2015.1066.
- Kim, Tae Min, Ahnah Song, Dong-Wan Kim, Soyeon Kim, Yong-Oon Ahn, Bhumsuk Keam, Yoon Kyung Jeon, Se-Hoon Lee, Doo Hyun Chung, and Dae Seog Heo. 2015. “Mechanisms of Acquired Resistance to AZD9291”. Journal of Thoracic Oncology. Elsevier BV. doi:10.1097/jto.0000000000000688.
- Ahn, Myung‐Ju, Chun‐Ming Tsai, Frances A. Shepherd, Lyudmila Bazhenova, Lecia V. Sequist, Toyoaki Hida, James C. H. Yang, et al.. 2018. “Osimertinib in Patients with T790M Mutation‐positive, Advanced Non–small Cell Lung Cancer: Long‐term Follow‐up from a Pooled Analysis of 2 Phase 2 Studies”. Cancer. Wiley. doi:10.1002/cncr.31891.
- Thress, Kenneth S., Vivien Jacobs, Helen K. Angell, James Chih-Hsin Yang, Lecia V. Sequist, Fiona Blackhall, Wu-Chou Su, et al.. 2017. “Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial”. Journal of Thoracic Oncology. Elsevier BV. doi:10.1016/j.jtho.2017.07.011.
- Ballard, Peter, James W.T. Yates, Zhenfan Yang, Dong-Wan Kim, James Chih-Hsin Yang, Mireille Cantarini, Kathryn Pickup, et al.. 2016. “Preclinical Comparison of Osimertinib with Other Egfr-tkis in Egfr-mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity”. Clinical Cancer Research. American Association for Cancer Research (AACR). doi:10.1158/1078-0432.ccr-16-0399.
- Thress, Kenneth S., Roz Brant, T. Hedley Carr, Simon Dearden, Suzanne Jenkins, Helen Brown, Tracey Hammett, Mireille Cantarini, and J. Carl Barrett. 2015. “EGFR Mutation Detection in Ctdna from NSCLC Patient Plasma: A Cross-platform Comparison of Leading Technologies to Support the Clinical Development of AZD9291”. Lung Cancer. Elsevier BV. doi:10.1016/j.lungcan.2015.10.004.
- Oxnard, Geoffrey R., Yuebi Hu, Kathryn F. Mileham, Hatim Husain, Daniel B. Costa, Philip Tracy, Nora Feeney, et al.. 2018. “Assessment of Resistance Mechanisms and Clinical Implications in Patients Withegfrt790m–positive Lung Cancer and Acquired Resistance to Osimertinib”. JAMA Oncology. American Medical Association (AMA). doi:10.1001/jamaoncol.2018.2969.
- Dearden, Simon, Helen Brown, Suzanne Jenkins, Kenneth S. Thress, Mireille Cantarini, Rebecca Cole, Malcolm Ranson, and Pasi A. Jänne. 2017. “EGFR T790M Mutation Testing Within the Osimertinib AURA Phase I Study”. Lung Cancer. Elsevier BV. doi:10.1016/j.lungcan.2017.04.011.
- Jänne, Pasi A., James Chih-Hsin Yang, Dong-Wan Kim, David Planchard, Yuichiro Ohe, Suresh S. Ramalingam, Myung-Ju Ahn, et al.. 2015. “AZD9291 in EGFR Inhibitor–resistant Non–small-cell Lung Cancer”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1411817.
- Martin, Mona L., Julia Correll, Andrew Walding, and Anna Rydén. 2021. “How Patients Being Treated for Non-small Cell Lung Cancer Value Treatment Benefit Despite Side Effects”. Quality of Life Research. Springer Science and Business Media LLC. doi:10.1007/s11136-021-02882-6.
- Ahn, Myung-Ju, Ji-Youn Han, Dong-Wan Kim, Byoung Chul Cho, Jin-Hyoung Kang, Sang-We Kim, James Chih-Hsin Yang, Tetsuya Mitsudomi, and Jong Seok Lee. 2020. “Osimertinib in Patients with T790m-positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies”. Cancer Research and Treatment. Korean Cancer Association. doi:10.4143/crt.2019.200.
- Kiura, Katsuyuki, Kiyotaka Yoh, Nobuyuki Katakami, Naoyuki Nogami, Kazuo Kasahara, Toshiaki Takahashi, Isamu Okamoto, Mireille Cantarini, Rachel Hodge, and Hirohiko Uchida. 2018. “Osimertinib in Patients with Epidermal Growth Factor Receptor T790M Advanced Non‐small Cell Lung Cancer Selected Using Cytology Samples”. Cancer Science. Wiley. doi:10.1111/cas.13511.
- Goss, G., C.-M. Tsai, F.A. Shepherd, M.-J. Ahn, L. Bazhenova, L. Crinò, F. de Marinis, et al.. 2018. “CNS Response to Osimertinib in Patients with T790m-positive Advanced NSCLC: Pooled Data from Two Phase II Trials”. Annals of Oncology. Elsevier BV. doi:10.1093/annonc/mdx820.
- Oxnard, Geoffrey R., Kenneth S. Thress, Ryan S. Alden, Rachael Lawrance, Cloud P. Paweletz, Mireille Cantarini, James Chih-Hsin Yang, J. Carl Barrett, and Pasi A. Jänne. 2016. “Association Between Plasma Genotyping and Outcomes of Treatment with Osimertinib (AZD9291) in Advanced Non–small-cell Lung Cancer”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2016.66.7162.
- Oxnard, Geoffrey R., Kenneth S. Thress, Ryan S. Alden, Rachael Lawrance, Cloud P. Paweletz, Mireille Cantarini, James Chih-Hsin Yang, J. Carl Barrett, and Pasi A. Jänne. 2016. “Association Between Plasma Genotyping and Outcomes of Treatment with Osimertinib (AZD9291) in Advanced Non–small-cell Lung Cancer”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.2016.66.7162.
- Thress, Kenneth S., Roz Brant, T. Hedley Carr, Simon Dearden, Suzanne Jenkins, Helen Brown, Tracey Hammett, Mireille Cantarini, and J. Carl Barrett. 2015. “EGFR Mutation Detection in Ctdna from NSCLC Patient Plasma: A Cross-platform Comparison of Leading Technologies to Support the Clinical Development of AZD9291”. Lung Cancer. Elsevier BV. doi:10.1016/j.lungcan.2015.10.004.
- Ballard, Peter, James W.T. Yates, Zhenfan Yang, Dong-Wan Kim, James Chih-Hsin Yang, Mireille Cantarini, Kathryn Pickup, et al.. 2016. “Preclinical Comparison of Osimertinib with Other Egfr-tkis in Egfr-mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity”. Clinical Cancer Research. American Association for Cancer Research (AACR). doi:10.1158/1078-0432.ccr-16-0399.
- Martin, Mona L., Julia Correll, Andrew Walding, and Anna Rydén. 2021. “How Patients Being Treated for Non-small Cell Lung Cancer Value Treatment Benefit Despite Side Effects”. Quality of Life Research. Springer Science and Business Media LLC. doi:10.1007/s11136-021-02882-6.
- Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.
- Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Janne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018 Nov 1;4(11):1527-1534. doi: 10.1001/jamaoncol.2018.2969.
- Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.
- Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Janne PA. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Mar 20;36(9):841-849. doi: 10.1200/JCO.2017.74.7576. Epub 2017 Aug 25.
- Thress KS, Jacobs V, Angell HK, Yang JC, Sequist LV, Blackhall F, Su WC, Schuler M, Wolf J, Gold KA, Cantarini M, Barrett JC, Janne PA. Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial. J Thorac Oncol. 2017 Oct;12(10):1588-1594. doi: 10.1016/j.jtho.2017.07.011. Epub 2017 Jul 24.
- Dearden S, Brown H, Jenkins S, Thress KS, Cantarini M, Cole R, Ranson M, Janne PA. EGFR T790M mutation testing within the osimertinib AURA Phase I study. Lung Cancer. 2017 Jul;109:9-13. doi: 10.1016/j.lungcan.2017.04.011. Epub 2017 Apr 19.
- Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, Pickup K, Jordan A, Hickey M, Grist M, Box M, Johnstrom P, Varnas K, Malmquist J, Thress KS, Janne PA, Cross D. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res. 2016 Oct 15;22(20):5130-5140. doi: 10.1158/1078-0432.CCR-16-0399. Epub 2016 Jul 19.
- Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Janne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Oct 1;34(28):3375-82. doi: 10.1200/JCO.2016.66.7162. Epub 2016 Jun 27.
- Yu HA, Tian SK, Drilon AE, Borsu L, Riely GJ, Arcila ME, Ladanyi M. Acquired Resistance of EGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor: Emergence of a Third Mutation (C797S) in the EGFR Tyrosine Kinase Domain. JAMA Oncol. 2015 Oct;1(7):982-4. doi: 10.1001/jamaoncol.2015.1066. No abstract available.
- Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817.
- Martin ML, Correll J, Walding A, Ryden A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.
- 2013. "AZD9291 First Time In Patients Ascending Dose Study". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01802632.
Frequently Asked Questions
What is the maximum age limit for participants of this research?
"The trial organisers are searching for individuals of 18 years or older, but under 130 years in age." - Anonymous Online Contributor
Unverified Answer
What is the aggregate amount of participants in this clinical trial?
"At this juncture, this trial does not require any additional enrolment. The first post was made on March 4th 2013 and the last update occurred November 10th 2022. If you are in search of other studies related to lung cancer, 1908 clinical trials have open slots while 101 medical centres offer AZD9291 treatment opportunities." - Anonymous Online Contributor
Unverified Answer
What other trials have been conducted utilizing AZD9291 as a therapeutic agent?
"Currently, 101 AZD9291 studies are in progress. 17 of them have reached Phase 3 status while the rest remain at earlier stages. 4699 medical facilities across the United States, with a main hub based in Uniondale New York, are recruiting patients for these trials." - Anonymous Online Contributor
Unverified Answer
How many locales have been chosen for this scientific investigation?
"The present iteration of this clinical trial is recruiting participants from 6 medical centres, including those in Houston, Atlanta and Boston to name a few. To reduce the burden associated with travel for potential volunteers, it is advised to consider sites closest geographically." - Anonymous Online Contributor
Unverified Answer
Is this a pioneering clinical trial?
"Presently, 101 clinical trials for AZD9291 are taking place in 1059 cities and 51 nations. AstraZeneca sponsored the initial test of this medication back in 2013; 603 patients participated across Phase 1 & 2 drug approval stages. Since then, 30 studies have concluded successfully." - Anonymous Online Contributor
Unverified Answer
What criteria must potential participants meet to be eligible for this clinical investigation?
"This clinical trial is seeking 603 individuals aged between 18 and 130 suffering from lung cancer. Participants must also fulfil the following criteria: evidence of disease progression whilst on continuous EGFR TKI treatment; confirmation that tumours harbour an EGFR mutation linked to sensitivity towards such drugs (e.g G719X, exon 19 deletion, L858R or L861Q); documented clinically benefit from a previous round of ERFGR therapy per Jackman et al 2010 followed by systemic objective regression as specified in RECIST/WHO guidelines; women should be using contraceptive devices and have taken a negative pregnancy test prior to dosing comm" - Anonymous Online Contributor
Unverified Answer
Does this investigation currently require participants?
"As documented on clinicaltrials.gov, the recruitment for this medical trial has been concluded. It was initially posted in March 2013 and its information was last modified in November 2022; nevertheless, there are 2,009 other studies that have opened their enrollment process at present." - Anonymous Online Contributor
Unverified Answer