449PD - Updated safety and efficacy from a phase I study of AZD9291 in patients (pts) with EGFR-TKI-resistant non-small cell lung cancer (NSCLC)

Date 28 September 2014
Event ESMO 2014
Session Developmental therapeutics
Topics Clinical Research
Translational Research
Non-Small Cell Lung Cancer
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter James Yang
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors J. Yang1, D. Kim2, D. Planchard3, Y. Ohe4, S.S. Ramalingam5, M. Ahn6, S. Kim7, W. Su8, L. Horn9, D. Haggstrom10, E. Felip11, J. Kim12, P. Frewer13, M. Cantarini14, S. Ghiorghiu14, M. Ranson15, P.A. Janne16
  • 1Department Of Oncology, National Taiwan University Hospital, TW-100 - Taipei/TW
  • 2Department Of Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 3Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 4Thoracic Oncology, National Cancer Center Hospital East, JP-277-8577 - Kashiwa/JP
  • 5Winship Cancer Institute, Emory University, 30322 - Atlanta/US
  • 6Division Of Hematology/oncology, Department Of Medicine, Sungkyunkwan University School of Medicine Samsung Medical Center, 135-710 - Seoul/KR
  • 7Oncology, Asan Medical Center, Seoul/KR
  • 8Department Of Internal Medicine, National Cheng Kung University Medical College and Hospital, 704 - Tainan/TW
  • 9Thoracic Oncology Program, Vanderbilt-Ingram Cancer Center, Nashville/US
  • 10Medical Oncology, Levine Cancer Institute, Charlotte/US
  • 11Thoracic Oncology Unit, Oncology Department, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 12Department Of Medical Oncology, Yonsei University College of Medicine, KR-120-752 - Seoul/KR
  • 13Early Clinical Development, AstraZeneca, Macclesfield/GB
  • 14Global Medicines Development, AstraZeneca, Macclesfield/GB
  • 15Department Of Medical Oncology, Formerly at University of Manchester Christie Hospital NHS Trust, Manchester/GB
  • 16Thoracic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US



AZD9291 is a potent, selective, irreversible EGFR-TKI, effective against the EGFR-TKI-sensitising (EGFRm+) and resistance T790M mutations. Here we report updated data from the ongoing Phase I study of AZD9291 in pts with EGFRm+ NSCLC (AURA; NCT01802632).


Pts with EGFRm+ NSCLC and acquired resistance to EGFR-TKIs were enrolled in a multicentre trial into dose escalation and expansion cohorts. AZD9291 was administered orally, at doses of 20–240 mg once daily. Stable brain metastases were allowed. Primary objective was safety and tolerability; anti-tumour activity was a secondary objective. Prospective mandatory central T790M testing was required in the expansion cohorts and was optional for dose escalation cohorts.


As of 2 April 2014, 232 pts (female 63%, median age 60, Asian/Caucasian 64%/34%, immediate prior EGFR-TKI therapy 60%) were enrolled: 31 pts in the dose escalation and 201 pts in the dose expansion cohorts, of whom 120 were T790M+ by central tumour testing. Adverse events (AEs) were mostly mild (CTCAE Grade 1/2), with diarrhoea (39%), rash (36%) and nausea (18%) the most commonly reported. 8 pts (3%) had dose reductions. Grade ≥3 AEs occurred in 24% of pts. There were 8 ILD-like reports. At the recommended Phase II dose of 80 mg QD, rash and diarrhoea occurred in 27% (Grade 3, 0%) and 20% (Grade 3, 1%) of pts, respectively. Among all evaluable pts to date, RECIST responses were observed at all dose levels. The confirmed overall response rate (ORR) in patients with centrally tested EGFR T790M+ tumours was 56% (56/100; 95% CI 46, 66%) and in patients with EGFR T790M- tumours the confirmed ORR was 17% (8/48; 95% CI 8, 30%). In 56 pts with EGFR T790M+ tumours and confirmed response: longest duration of response to date was ongoing at approx 7.5 months; 7/56 pts responded for at least >6 months and 46/56 have an ongoing response <6 months. Updated results will be presented.


AZD9291 has been well tolerated at all dose levels tested. Clinical activity has been shown in pts with centrally confirmed EGFR T790M+ NSCLC, with durable responses of >6 months.


J.C. Yang: Advisory board: Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Merck, Bayer, Clovis Oncology. Corporate-sponsored research: Boehringer Ingelheim; D. Planchard: Advisory boards: AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Roche, BMS S.S. Ramalingam: Advisory boards: AstraZeneca, Boehringer Ingelheim, Genentech; L. Horn: Research funding: Astellas. Compensated advisory boards: Bristol-Myers Squibb, Clovis, Helix Bio. Uncompensated advisory boards: PUMA, Xcovery. Steering Committee (uncompensated): Bayer. Honoraria: Boehringer Ingelheim; E. Felip: Advisory boards: Boehringer Ingelheim, Novartis, Roche, BMS, Lilly; P. Frewer, M. Cantarini and S. Ghiorghiu: Employment and stock ownership: AstraZeneca; M. Ranson: Advisory boards: AstraZeneca; P.A. Janne: Consultant or advisory role: AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Pfizer, Merrimack Pharmaceuticals, Chugai, Immunogen. Stock ownership: Gatekeeper. Other: Lab Corp. All other authors have declared no conflicts of interest.