AstraZeneca unveils further evidence for AZD9291 potential in first-line and pre-treated NSCLC

The data being presented today at the World Conference on Lung Cancer (WCLC) 2015 were from the AURA Phase I trial first-line cohort and two AURA Phase II studies.

Data in the first-line setting demonstrated that in 60 patients who received AZD9291 once daily 72% (95% confidence interval (CI) 58% to 82%) were progression free (PFS) at 12 months. Confirmed overall response rate (ORR) was 75% (95% CI 62% to 85%). The longest duration of response (DoR) was ongoing at 18 months.1

"While the data are still preliminary, these latest results from the AURA trial first-line cohort further reinforce the potential of AZD9291 in treatment-naïve EGFRm advanced NSCLC patients," said Professor Suresh S. Ramalingam, presenting author of the AURA trial first-line cohort data and Chief of Thoracic Oncology and Director of Medical Oncology, Emory University School of Medicine, Atlanta, GA.

Data on two AURA Phase II studies (AURA extension and AURA2) in previously treated patients with EGFR T790M mutation were also presented. While still preliminary, these studies showed an efficacy and tolerability profile for AZD9291 consistent with previously reported data. In AURA extension (n=201), ORR was 61% (95% CI 54% to 68%); median DoR and median PFS were not calculable (NC). Consistent results were observed in AURA2 (n=210), ORR was 71% (95% CI 64% to 77%); median DoR was 7.8 months (95% CI 7.1 months to NC) and median PFS was 8.6 months (95% CI 8.3 months to 9.7 months). 2-3

AstraZeneca head of oncology, global medicines development Antoine Yver said: "These data provide further evidence of the encouraging durable response with AZD9291 in treatment-naïve and pre-treated patients with advanced EGFRm NSCLC.

"The data support our accelerated development strategy with AZD9291, which has moved with unprecedented speed from first human studies to the US Food and Drug Administration and other regulatory submissions. With AZD9291 now under review by global regulatory authorities, we are on track to bring this innovative medicine to patients as quickly as possible to address this critical need."

The safety profile of AZD9291 in these studies was in line with that reported earlier in the year. In the AURA first-line cohort, the most common all-cause adverse events (AE) of any grade across different dose groups included rash (grouped terms) (77% all grades, 2% Grade =3) and diarrhea (73% all grades, 3% Grade =3). These AEs were also reported as the most common in the two AURA Phase II studies (AURA extension, rash 40% all grades, 1% Grade =3, diarrhea 45% all grades, 1% Grade =3; AURA 2, rash 42% all grades, 1% Grade =3, diarrhea 39% all grades, 1% Grade =3).1-3

Hyperglycemia, interstitial lung disease (ILD) and QT prolongation remain consistent with data previously presented. In the AURA first-line cohort, ILD (grouped terms) was 5% all grades, 0% Grade =3; hyperglycemia was 5% all grades, 0% Grade =3; and, QT prolongation was 8% all grades, 0% Grade =3. In the two AURA Phase II studies, AURA extension, ILD (grouped terms) was 4% all grades, 3% Grade =3; hyperglycemia was 1% all grades, 1% Grade =3; and, QT prolongation was 3% all grades, 0% Grade =3. For AURA 2, ILD (grouped terms) was 2% all grades, 1% Grade =3; hyperglycemia was 1% all grades, 0% Grade =3; and, QT prolongation was 5% all grades, 2% Grade =3.

In addition, encouraging pre-clinical data were presented suggesting AZD9291 may penetrate the blood-brain-barrier, prompting further investigation of AZD9291 in patients with EGFRm NSCLC with brain metastases.

Marketing authorization applications for AZD9291 for the treatment of EGFR T790M mutation-positive NSCLC have been submitted to the US Food and Drug Administration (FDA). Recently, the FDA granted Priority Review to AZD9291, adding to the Breakthrough Therapy designation, Orphan Drug and Fast Track status already assigned by the regulatory body.