AstraZeneca PLC’s TAGRISSO Met Primary Endpoint in Late-Stage Lung Cancer Trial

TAGRISSO demonstrated superior progression-free survival compared to standard platinum-based chemotherapy, with a safety profile consistent with previous trials

First randomized trial to evaluate the clinical benefit of an EGFR T790M medicine, and data are consistent with those supporting TAGRISSO approvals

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced that the AURA3 Phase III trial met its primary endpoint, demonstrating superior progression-free survival (PFS) compared to standard platinum-based doublet chemotherapy. The AURA3 randomized trial assessed the efficacy and safety of TAGRISSO^® (osimertinib) as a second-line treatment in more than 400 patients with EGFR T790M mutation-positive, locally-advanced or metastatic NSCLC, whose disease had progressed following first-line EGFR tyrosine kinase inhibitor (TKI) therapy. TAGRISSO also demonstrated a safety profile consistent with previous trials.

In addition to PFS, the objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) also achieved clinically meaningful improvement versus chemotherapy. A full evaluation of AURA3 data, including an analysis of overall survival (OS), is ongoing, and results will be presented at an upcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “These results confirm TAGRISSO as a meaningful alternative to benefit EGFR T790M lung cancer patients. The AURA3 results demonstrate the benefits of our science-led approach that enabled the rapid development of TAGRISSO as a targeted treatment to address the most common cause of resistance to a first-generation EGFR-TKI for patients with metastatic EGFR-mutant lung cancer. We remain committed to exploring the potential of TAGRISSO to further extend its reach and help meet patient need.”

TAGRISSO is one of the fastest development programs ever, from start of clinical trials to approval in just over two and a half years. It was approved in the US, EU, Japan, Canada, Switzerland, Israel and Mexico as the first treatment for patients with EGFR T790M mutation-positive locally advanced/metastatic NSCLC. TAGRISSO is also approved in South Korea in the same indication. Eligibility for treatment with TAGRISSO is dependent on confirmation that the EGFR T790M mutation is present in the tumor.

AstraZeneca is committed to exploring the full potential of TAGRISSO along with the rest of our outstanding oncology portfolio.

IMPORTANT SAFETY INFORMATION

• There are no contraindications for TAGRISSO
• Interstitial Lung Disease (ILD)/Pneumonitis occurred in 3.3% and was fatal in 0.5% of 813 TAGRISSO patients. Withhold TAGRISSO and promptly investigate for ILD in any patient presenting with worsening of respiratory symptoms indicative of ILD (e.g., dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
• QTc interval prolongation occurred in TAGRISSO patients. Of the 411 patients in two Phase II studies, 0.2% were found to have a QTc greater than 500 msec, and 2.7% had an increase from baseline QTc greater than 60 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life threatening arrhythmia
• Cardiomyopathy occurred in 1.4% and was fatal in 0.2% of 813 TAGRISSO patients. Left Ventricular Ejection Fraction (LVEF) decline >10% and a drop to <50% occurred in 2.4% of (9/375) TAGRISSO patients. Assess LVEF before initiation and then at 3 month intervals of TAGRISSO treatment. Withhold TAGRISSO if ejection fraction decreases by 10% from pretreatment values and is less than 50%. For symptomatic congestive heart failure or persistent asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue TAGRISSO
• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during TAGRISSO treatment and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
• The most common adverse reactions (>20%) observed in TAGRISSO patients were diarrhea (42%), rash (41%), dry skin (31%) and nail toxicity (25%)

INDICATION

TAGRISSO is indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

AURA3, an open label, randomized Phase III study designed to assess the efficacy and safety of osimertinib (AZD9291) versus platinum-based doublet chemotherapy in patients with EGFR T790M positive, locally advanced, or metastatic NSCLC who have progressed following prior therapy with an EGFR-TKI, is the key confirmatory trial for osimertinib.

Please see complete Prescribing Information including Patient Information.

NOTES TO EDITORS

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, more than breast, prostate and colorectal cancers combined. Lung cancer has a five-year survival rate that is less than 20%. Approximately 85% of all lung cancers in the US are NSCLC; 10% to 15% of these are EGFR mutation-positive. Approximately two-thirds of patients treated with EGFR TKI therapy will acquire resistance related to the T790M mutation.

About TAGRISSO^® (osimertinib)

TAGRISSO (osimertinib) 80mg once-daily tablet is the first medicine indicated for the treatment of metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy. TAGRISSO is as an irreversible EGFR inhibitor, born out of scientific exploration and engineered to combat the mechanism of resistance by targeting the T790M resistance mutation.

About AURA3

AURA3 compared the efficacy and safety of TAGRISSO 80mg once daily and platinum-based doublet chemotherapy in 419 patients with EGFR T790M mutation-positive, locally-advanced or metastatic NSCLC whose disease had progressed on or after treatment with a previous EGFR-TKI. The trial was carried out in more than 130 locations worldwide, including the US, Canada, Europe, China, Japan, Korea, Taiwan and Australia.

The primary endpoint of the trial is PFS, and secondary endpoints include OS, ORR, DoR, DCR, safety and measures of health-related quality of life (HRQoL).

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least 6 new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms -- immuno-oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates -- and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – oncology; respiratory and autoimmunity; and cardiovascular and metabolic disease. We are also active in infection, neuroscience and inflammatory diseases through collaborations with others. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca-us.com