AstraZeneca announces efficacy and safety data for AZD9291 in first-line treatment of EGFRm advanced NSCLC

Over 80% of patients progression free at 9 months in the first-line treatment of advanced non-small cell lung cancer

AstraZeneca today announced preliminary efficacy and safety data for AZD9291 in the first-line treatment of epidermal growth factor receptor mutation positive (EGFRm) advanced non-small cell lung cancer (NSCLC). Data showed that 81% (95% confidence interval (CI) 68% to 89%) of patients on a once daily dose of AZD9291 were progression free at 9 months; overall response rate was 73% (95% CI 60% to 84%). The longest duration of response was ongoing at 13.8 months at the time of data cutoff.

The data from the first-line expansion cohorts of the AURA Phase I study were presented at the annual meeting of the American Society of Clinical Oncology in Chicago. The first-line cohorts included 60 patients with EGFRm advanced NSCLC who received AZD9291 80mg or 160mg once daily. The data are not fully mature with an approximate 11 month median follow up in the 80mg cohort, and an approximate 8.5 month median follow up in the 160mg cohort. The most common adverse events in both cohorts included rash (Grade 3: 0% at 80mg, 3% at 160mg) and diarrhoea (Grade 3: 0% at 80mg, 7% at 160mg).

“These preliminary data demonstrate the potential of AZD9291 in treatment-naïve advanced NSCLC patients with EGFR mutation. These promising results with AZD9291 will be studied further by the ongoing Phase III FLAURA trial in the first-line setting,” said Professor Suresh S. Ramalingam, Chief of Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA, who presented the AURA 1L data and is lead principal investigator for the FLAURA study.

The first-line data from the AURA study build on findings presented in April at the European Lung Cancer Congress (ELCC). Data presented at ELCC showed that previously treated patients with EGFRm advanced NSCLC who also have the T790M resistance mutation achieved a median progression-free survival (PFS) of 13.5 months (95% CI 8.3 months to not calculable) on AZD9291 80mg once daily, based on 38% of patients having tumour progression. Patients with EGFRm NSCLC are particularly sensitive to treatment with currently available EGFR tyrosine kinase inhibitors (TKIs). However, tumours almost always develop resistance to treatment, leading to disease progression. In approximately two thirds of patients treated with the approved EGFR-TKIs, gefitinib or erlotinib, this resistance is caused by the secondary T790M mutation.

Antoine Yver, Head of Oncology, Global Medicines Development, said:

The promising response to first-line treatment with AZD9291 builds on the encouraging efficacy already seen in patients with EGFRm advanced NSCLC who have the T790M resistance mutation, and whose disease has progressed following previous treatment with first-generation EGFR tyrosine kinase inhibitors. We have just been granted accelerated assessment for our upcoming regulatory submission for AZD9291 in Europe. We remain confident that AZD9291 has the potential to deliver early and durable efficacy by targeting both activating and resistance EGFR mutations.

AZD9291 is being investigated across different lines of therapy, both as monotherapy and in combination with other small molecule and immuno-oncology investigational medicines, to understand its potential benefit for overcoming newly-identified forms of resistance for a broader range of patients. The ongoing TATTON study will investigate the combination of MEDI4736 (anti-PD-L1 immune checkpoint inhibitor), selumetinib (MEK inhibitor), or savolitinib (MET inhibitor; AZD6094) in lung cancer. Data presented at ASCO from the TATTON study showed that AZD9291 has a tolerable safety profile, supporting its investigation in potentially synergistic combinations with other molecules. A Phase III study (CAURAL) investigating AZD9291 in combination with MEDI4736 as a potential second-line treatment for EGFRm NSCLC patients with the T790M resistance mutation is also planned to start later this year, as part of AstraZeneca’s combination focused development strategy.