OREANDA-NEWS. AstraZeneca today announced latest data from the ongoing AURA study of AZD9291 in patients with advanced epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC), who also have the T790M resistance mutation. The data demonstrated a median progression free survival (PFS) of 13.5 months (95% confidence interval (CI) 8.3 months to not calculable (NC))1. These PFS findings relate to independently reviewed data from 63 patients with T790M tumours treated with AZD9291 at a dose of 80mg per day, and are based on only 38% of patients having tumour progression.

The updated data also show an overall response rate with AZD9291 80mg of 54% (95% CI 41% to 67%) and a median duration of response of 12.4 months (95% CI 8.3 months to NC).

Presenting the latest analysis at the European Lung Cancer Conference (ELCC) 2015 in Geneva, Switzerland, AURA principal investigator Dr Pasi A. J?nne MD, PhD, Director, Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute and Professor of Medicine Harvard Medical School, emphasised the sustained activity of AZD9291 as indicated by the key parameters of patient response: “There are few treatment options currently available for patients with advanced EGFRm non-small cell lung cancer who experience disease progression due to a second mutation known as T790M. Management is usually limited to chemotherapy or re-challenge with EGFR tyrosine kinase inhibitors. As AURA continues to mature, and the trend in progression free survival and durable clinical response is maintained, this may support the potential for AZD9291 as a future treatment option for advanced EGFRm NSCLC.”

AZD9291 is a once daily, selective, irreversible EGFR tyrosine kinase inhibitor (TKI) designed to target both the activating sensitising mutation, EGFRm, and T790M, the genetic mutation responsible for EGFR TKI treatment resistance in up to approximately two-thirds of cases of EGFRm advanced NSCLC. There are currently no treatments specifically approved for patients with EGFRm T790M advanced NSCLC.

Antoine Yver, Head of Oncology, Global Medicines Development, AstraZeneca, said: “We are committed to developing novel medicines that address the significant unmet need in lung cancer by focusing on the genetic drivers underlying the disease. We are on track for a regulatory submission of AZD9291 in the US in the second quarter of this year. Our extensive clinical research programme is also investigating the potential of AZD9291 in earlier disease and in combination with other pipeline assets including immuno-oncology molecules. With this comprehensive approach, our goal is to develop a broad range of potential treatment options for patients with EGFR mutation positive non-small cell lung cancer.”

The ongoing AURA Phase I/II study is investigating AZD9291 in patients with advanced NSCLC and disease progression following treatment with an EGFR TKI. As of 2 December 2014, 283 patients with EGFRm advanced NSCLC and acquired resistance to EGFR TKIs were enrolled – 31 patients in dose escalation and 252 patients in expansion cohorts. Of these patients, 163 had T790M tumours confirmed by central testing1. The updated results presented at ELCC build on previously reported data presented at the European Society for Medical Oncology 20142.

In patients treated with AZD9291 80mg, the most common all-cause adverse events (AEs) of any grade were rash, 38% (0% Grade ?3) and diarrhea, 36% (1% Grade ?3). Investigator-determined treatment-related Grade ?3 AEs occurred in 14% of patients.

As of 19 March 2015, of more than 1000 patients across all studies dosed with AZD9291, interstitial lung disease (ILD) grouped term events were reported in approximately 2.7% of patients (27 events): 12 common terminology criteria for adverse events (CTCAE) grade 1–2; 13 grade ?3; 2 currently ungraded. Of these, a total of 3 patients were reported to have died due to ILD (Grade 5).

AstraZeneca is currently also investigating AZD9291 as first line therapy for EGFRm NSCLC patients, and in combination with MEDI4736 (anti-PDL1 immunotherapy), selumetinib (MEK inhibitor) and AZD6094 (MET inhibitor) in NSCLC. Initial data will be presented at the American Society of Clinical Oncology (ASCO) annual meeting 2015.