AstraZeneca A/S

AstraZeneca has presented the full results of the Phase III FLAURA trial, which support Tagrisso’s (osimertinib) clearpotential as a new standard of care (SoC) in the 1st-line treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).

Results of the Phase III FLAURA trial were included at the Presidential Symposium I of the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, and demonstrate a superior, clinically-meaningful PFS advantage with Tagrisso compared with current SoC EGFR-TKIs (erlotinib or gefitinib).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The FLAURA data are truly exciting. Until now, even with the therapeutic advances offered by the first- and second-generation EGFR inhibitors, less than 20% of EGFR mutation-positive NSCLC patients survive for five years. The FLAURA data suggest early and sustained benefit with Tagrisso that has the potential to significantly impact long-term patient outcomes and help address the considerable unmet need that remains.”

Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from the Winship Cancer Institute of Emory University, Atlanta, USA, said: “The FLAURA data for osimertinib are likely to result in a major paradigm shift in the treatment of patients with EGFR mutation-positive advanced lung cancer. Not only did the trial demonstrate a robust improvement in efficacy with osimertinib when compared to other commonly-used EGFR inhibitors, the side effects profile was also more favourable with osimertinib”.

Summary of key efficacy results:

Endpoint	Tagrisso	SoC	Hazard ratio (HR)/ Odds ratio (OR)
PFS (primary endpoint)	18.9 months (median)	10.2 months (median)	HR 0.46 95% CI, 0.37-0.57, p<0.0001
OS at 25% maturity	N/A	N/A	HR 0.63 95% CI, 0.45-0.88, p=0.0068*
Duration of Response (DoR)	17.2 months (median)	8.5 months (median)	N/A
Objective Response Rate (ORR)	80%	76%	OR 1.28 0.85-1.93, p=0.2335

*0.0015 was the threshold required for statistical significance at the current level of maturity. A final OS analysis is planned at a later stage.Additional highlights from the FLAURA data include:

Superior progression-free survival (PFS): Patients on Tagrisso had less than half the risk of progression or death compared with patients on erlotinib or gefitinib (hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.37-0.57; p<0.0001). The median PFS was 18.9 months for patients on Tagrisso vs.10.2 months for patients in the comparator arm.

Clinically-meaningful preliminary overall survival (OS) data at 25% maturity: The hazard ratio for OS was 0.63 (95% CI: 0.45-0.88; p=0.0068) favouring Tagrisso. Overall survival data were 25% mature at the time of the interim analysis (21% of the patients on Tagrisso had died and 30% of the patients on the comparator arm had died). The p-value of 0.0068 was not below the threshold of 0.0015 required for statistical significance at the current level of maturity. A final OS analysis is planned at a later stage.

PFS improvements consistent across subgroups: Improvements in PFS with Tagrisso were consistent across all pre-specified patient subgroups, with at least a 40% reduction in the risk of progression or death, including in patients with/without central nervous system (CNS) metastases at study entry, Asian/non-Asian patients, patients with/without prior smoking history, and patients with exon 19 deletion/L858R.

Impressive duration of response (DoR) and objective response rate (ORR): Patients treated with Tagrisso had more than double the median DoR than those on the comparator arm (17.2 months vs. 8.5 months), and an ORR (a measurement of tumour shrinkage) of 80% vs. 76% with the comparator arm (odds ratio 1.28 [0.85-1.93], p=0.2335).

The FLAURA safety data for Tagrisso were in line with those observed in prior clinical trials, with a low rate of Grade ≥3 adverse events (AEs). In patients treated with Tagrisso, the most common AEs were diarrhoea (58% [2% Grade ≥3]) and dry skin (32% [<1% Grade ≥3]), and in the comparator arm group, the most common AEs were diarrhoea (57% [3% Grade ≥3]) and dermatitis acneiform (48% [5% Grade ≥3]). Of the patients on Tagrisso, 33.7% had a Grade ≥3 AE, compared with 44.8% in the comparator arm, and 13.3% of patients on Tagrisso had an AE leading to treatment discontinuation compared with 18.1% in the comparator arm.

AstraZeneca is in discussions with global health authorities regarding regulatory submissions for Tagrisso based on the FLAURA data. A status of regulatory submissions is usually provided with the Company’s quarterly results announcement.

Tagrisso is currently approved in more than 50 countries, including the US, EU, Japan and China, as 2nd-line treatment for patients with advanced NSCLC who progress following treatment with an EGFR-TKI due to the EGFR T790M resistance mutation.

-ENDS-

Notes to Editors

About EGFR-mutated NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to EGFR-TKI treatment, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M. Tagrisso also targets this secondary mutation that leads to disease progression. There is also a need for agents with improved CNS efficacy, since approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About FLAURA

FLAURA assessed the efficacy and safety of Tagrisso 80mg orally once daily vs. standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was a double-blinded, randomised study, with 556 patients across 30 countries.

The primary endpoint of the trial was PFS, and secondary endpoints included OS, ORR, DOR, disease control rate (DCR), safety, and measures of health-related quality of life (HRQoL).

About Tagrisso

Tagrisso is a third-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations, with clinical activity against central nervous system (CNS) metastases. Tagrisso (osimertinib) 40mg and 80mg once-daily oral tablets have been approved in more than 50 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant and metastatic 1st-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing therapies to help every patient with lung cancer. We have two approved therapies and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

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 six 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 five 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 haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised 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 commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information, please visitwww.astrazeneca.comand follow us on Twitter @AstraZeneca.

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Approval-id: DK-2132

AstraZeneca and MedImmune, its global biologics research and development arm, have presented the full PFS data from a planned interim analysis of the Phase III PACIFIC trial. Results show that Imfinzi (durvalumab) demonstrated a statistically-significant and clinically-meaningful improvement in PFS compared to current standard of care with active surveillance in patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy (CRT).

Results of the Phase III PACIFIC trial, included at the Presidential Symposium I of the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, show an improvement in PFS of more than 11 months in patients treated with Imfinzi compared to placebo (full details in table below). The PFS improvement with Imfinzi was observed across all pre-specified subgroups, including PD-L1 expression status. Patients receiving Imfinzi also had a lower incidence of metastases than those receiving placebo. The PACIFIC trial continues to evaluate overall survival (OS), the other primary endpoint.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The Phase III PACIFIC results are incredibly encouraging for a patient population that until now has been without treatment options. As the first Immuno-Oncology medicine to achieve improvement in progression-free survival in this setting, Imfinzi is showing clear potential to become a new standard of care for patients with locally-advanced, unresectable NSCLC who have not progressed following chemoradiation.”

Dr. Luis Paz-Ares, Principal Investigator of the PACIFIC trial, from the Hospital Universitario Doce de Octubre, Madrid, Spain, said: “For patients with locally-advanced unresectable NSCLC who have completed chemoradiation therapy, Imfinzi represents a potential new treatment option in the context of clear unmet clinical need. Durvalumab overtly prolongs the period in which the disease is controlled with reasonable side effects. In addition, it offers hope to increase the cure rate in this setting, but more mature follow-up is needed to assess its impact on survival.”

Summary of key efficacy results:

Endpoint	Medicine	Value	Hazard ratio (HR)/ Confidence interval (CI)
PFS* (first primary endpoint)	Imfinzi	16.8 months (median)	HR 0.52 95% CI, 0.42-0.65, p<0.0001
Placebo	5.6 months (median)
Duration of response (DoR)	Imfinzi	Not reached	N/A
Placebo	13.8 months
Objective Response Rate (ORR) as measured from baseline scan post-CRT completion	Imfinzi	28.4%	95% CI, 24.28-32.89, p<0.001
Placebo	16.0%	95% CI, 11.31-21.59, p<0.001

* Time from randomisation to the first documented tumour progression, or death in the absence of progression. Randomisation in the PACIFIC trial occurred up to 6 weeks after completion of concurrent chemoradiation therapy (cCRT) and cCRT typically lasted at least 6 weeks. If the PFS had been measured prior to cCRT, it would add approximately 3 months or longer to the PFS value for each arm.Among patients receiving Imfinzi, the most frequent treatment-related adverse events (AEs) vs. placebo were cough (35.4% vs 25.2%), pneumonitis/radiation pneumonitis (33.9% vs 24.8%), fatigue (23.8% vs 20.5%), dyspnoea (22.3% vs 23.9%) and diarrhoea (18.3% vs 18.8%). 29.9% of patients experienced a grade 3 or 4 AE vs. 26.1% for placebo, and 15.4% of patients discontinued treatment due to AEs compared to 9.8% of patients on placebo.

On 31 July 2017, Imfinzi received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) as a potential treatment for patients with locally advanced, unresectable NSCLC whose disease has not progressed following platinum-based chemoradiation therapy.

AstraZeneca is in discussions with global health authorities regarding regulatory submissions for Imfinzi based on the PACIFIC data. A status of regulatory submissions is usually provided with the Company’s quarterly results announcement.

Imfinzi received accelerated approval from the US Food and Drug Administration for previously treated patients with advanced bladder cancer and is under review in Canada and Australia for similar use.

-ENDS-

Notes to Editors

About Locally Advanced (Stage III) NSCLC

Stage III lung cancer is divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to other organs.

Stage III lung cancer represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the G7 countries in 2016. More than half of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as sequential treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.

The trial is being conducted in 235 centres across 26 countries involving approximately 700 patients. The primary endpoints of the trial are progression-free survival (PFS) and overall survival (OS), and secondary endpoints include landmark PFS and OS, objective response rate (ORR) and duration of response.

About Imfinzi

Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour's immune-evading tactics and inducing an immune response.

Imfinzi continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in Immuno-Oncology. Imfinzi is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in metastatic urothelial cancer (mUC) and in head and neck squamous cell carcinoma (HNSCC). The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in NSCLC, SCLC, mUC and HNSCC and in Phase I/II trials in hepatocellular carcinoma and haematological malignancies.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing therapies to help every patient with lung cancer. We have two approved therapies and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

About AstraZeneca’s Approach to Immuno-Oncology (IO)

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the vast majority of patients.

We are pursuing a comprehensive clinical trial programme that includes Imfinzi (anti-PD-L1) monotherapy and in combination with tremelimumab (anti-CTLA-4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our oncology pipeline, and with those of our research partners, may provide new treatment options across a broad range of tumours.

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 six 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 five 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 haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About MedImmune

MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology; Respiratory, Cardiovascular & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK, and Mountain View, CA. For more information, please visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information, please visit www.astrazeneca.comand follow us on Twitter @AstraZeneca.

Media Relations Petra Eurenius	Nordic-Baltic MC	+46 709 186562
Esra Erkal-Paler	UK/Global	+44 203 749 5638
Karen Birmingham	UK/Global	+44 203 749 5634
Rob Skelding	UK/Global	+44 203 749 5821
Matt Kent	UK/Global	+44 203 749 5906
Jacob Lund	Sweden	+46 8 553 260 20
Michele Meixell	US	+1 302 885 2677
Investor Relations
Thomas Kudsk Larsen		+44 203 749 5712
Craig Marks	Finance, Fixed Income, M&A	+44 7881 615 764
Henry Wheeler	Oncology	+44 203 749 5797
Mitchell Chan	Oncology	+1 240 477 3771
Christer Gruvris	Diabetes; Autoimmunity, Neuroscience & Infection	+44 203 749 5711
Nick Stone	Respiratory; Brilinta	+44 203 749 5716
US toll free		+1 866 381 7277

Approval id: DK-2134