LBA3 - A phase I study of AZD9291 in patients with EGFR-TKI-resistant advanced NSCLC – updated progression free survival and duration of response data

Date 17 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Pasi Jänne
Citation Annals of Oncology (2015) 0 (0): 1-8. 10.1093/annonc/mdv128
Authors P.A. Jänne1, M. Ahn2, D. Kim3, S. Kim4, D. Planchard5, S.S. Ramalingam6, P. Frewer7, M. Cantarini8, S. Ghiorghiu9, J.C. Yang10
  • 1Lowe Center For Thoracic Oncology, Dana-Farber Cancer Institute, 02115-5450 - Boston/US
  • 2Department Of Internal Medicine, Hematology, Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 3Department Of Internal Medicine, Seoul National University Hospital (SNUH)-Yongon Campus, 110-744 - Seoul/KR
  • 4Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 5Department Of Medical Oncology (thoracic Unit) And Translational Research, Gustave Roussy, Villejuif/FR
  • 6Department Of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta/US
  • 7Ecd Biometrics, Astra Zeneca, Macclesfield/UK
  • 8Global Medicines Department, Oncology, Astra Zeneca, Macclesfield/UK
  • 9Global Medicines Development, Astra Zeneca, Hertfordshire/UK
  • 10Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW



Objectives / background

AZD9291 is a selective, irreversible EGFR-TKI, effective against EGFR-TKI-sensitising (EGFRm) and resistance T790M mutations. We report updated data from the global, multicentre, Phase I study (AURA; NCT01802632) of AZD9291 in patients (pts) with EGFRm advanced NSCLC (aNSCLC).


Pts with EGFRm aNSCLC and acquired resistance to EGFR-TKIs were enrolled into dose escalation and expansion cohorts. AZD9291 was given orally, at doses of 20–240 mg once daily. Prospective T790M testing was required in the expansion cohorts and optional for dose escalation cohorts. Pts with stable brain metastases were allowed. The primary objective was to investigate safety, tolerability and efficacy (objective response rate, ORR). Secondary objectives included assessment of anti-tumour activity by evaluation of duration of response (DoR), progression-free survival (PFS) using RECIST v1.1 and efficacy endpoints by independent central review.


As of 2 December 2014, 283 pts (female 62%, median age 60, Asian/Caucasian 61%/31%, immediate prior EGFR-TKI therapy 62%) were enrolled: 31 pts in dose escalation and 252 pts in expansion cohorts, 163 had T790M positive tumours by central testing. Adverse events (AEs) were mostly mild (CTCAE Gr 1/2), with diarrhoea (50%) and rash (46%) the most commonly reported. Investigator-determined treatment-related Gr ≥3 AEs occurred in 17% of pts. Investigator-assessed (Inv-A) confirmed ORR: T790M positive, 59% (92/157; 95% CI 51, 66%); T790M negative 23% (16/69; 95% CI 14, 35%). At the recommended Phase II dose of 80 mg, T790M positive cohort, Inv-A data were: confirmed ORR, 66% (95% CI 52, 77); median DoR, not calculable (NC; 95% CI 8.2, NC); median PFS, 10.9 mo (95% CI 8.3, NC; 40% maturity, 25/63 events). In the T790M positive 80 mg cohort, centrally reviewed data were: confirmed ORR, 54% (32/59; 95% CI 41, 67%); median DoR, 12.4 mo (95% CI 8.3, NC); median PFS, 13.5 mo (95% CI 8.3, NC; 38% maturity, 24/63 events).


AZD9291 has a manageable tolerability profile. In this Phase I study, investigator assessed and centrally reviewed data suggest encouraging DoR (NC and 12.4 mo, respectively) and PFS (10.9 and 13.5 mo, respectively).


P.A. Jänne: Consulting fees: Astra Zeneca, Boehringer Ingelheim, Clovis, Genentech, Roche, Chugai and Merrimack Pharmaceuticals. Post-marketing royalties from DFCI owned patent on EGFR mutations licensed to Lab Corp; stock ownership in Gatekeeper Pharmaceuticals. D.-W. Kim: Consultancy fees: Novartis. S.S. Ramalingam: Consultancy fees: Astra Zeneca, Eli Lilly, Bristol Myers Squibb, Novartis, Boehringer Ingelheim and Clovis Oncology. P. Frewer, M. Cantarini and S. Ghiorghiu: Employee and Shareholder of AstraZeneca. J.C.-H. Yang: Consultation fees : Astrazeneca, Roche/Genetech, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Novartis, Bayer, MSD, Merck, Pfizer, Astellas, Daichi-Sankyo, Celgene, Ono pharmaceuticals. All other authors have declared no conflicts of interest.

Clinical trial identification

NCT01802632 (23 February 2013)