Durvalumab Monotherapy Demonstrates Efficacy in Urothelial Bladder Cancer

Data show objective response rate (ORR) of 31% in all-evaluable patients and 46% in patients with PD-L1-high-expressing tumors1

PD-L1 expression correlates with response to durvalumab monotherapy per Ventana SP263 assay1

Results follow US FDA's recent Breakthrough Therapy Designation for durvalumab in patients with PD-L1 positive inoperable or metastatic urothelial bladder cancer2

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca and its global biologics research and development arm, MedImmune, today announced efficacy and safety data for durvalumab, an investigational, selective, human monoclonal antibody directed against programmed-death ligand-1 (PD-L1), in patients with advanced urothelial bladder cancer (UBC).

Preliminary results of the Phase I/II trial, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, showed an objective response rate (ORR) of 31% in all-evaluable patients (95% confidence interval (CI): 18%-47%) and 46% (95% confidence interval (CI): 28%-66%) in patients with PD-L1-high-expressing* tumors.1 Disease control rate (DCR), defined as confirmed complete or partial response or stable disease for 12 or more weeks, was 48% (95% CI: 32%-64%) in all-evaluable patients, and 57% (95% CI: 37%-76%) in patients with PD-L1-high-expressing tumors.1 Median duration of response had not yet been reached.1

David Berman, Senior Vice President, Head of Oncology Innovative Medicines, at MedImmune, said: "The efficacy data for durvalumab monotherapy in second-line bladder cancer are very encouraging, and confirm confidence in our diagnostic assay where the magnitude of response to durvalumab is clearly linked to PD-L1 expression. We look forward to continued exploration of durvalumab's potential in our first-line bladder cancer trial, DANUBE, both as monotherapy and in combination with tremelimumab."

Durvalumab 10mg/kg was administered every two weeks intravenously for up to 12 months, and demonstrated a safety profile among all patients (n=61).1 The most common adverse events reported in 5% or more of patients and which were all grade 1 or 2 included: fatigue (13%), diarrhea (10%), decreased appetite (8%), arthralgia (7%), asthenia (7%), nausea (7%) and pyrexia (7%).1 Three patients experienced treatment-related Grade 3 adverse events (1 acute kidney injury, 1 infusion-related reaction and 1 tumor flare).1

Dr. Christophe Massard, Head of Early Clinical Trials at the Institut Gustave Roussy, Villejuif, France said: "These positive preliminary data continue to support durvalumab's clinical efficacy and safety for the treatment of bladder cancer, and confirm durvalumab as a potential breakthrough therapy for a patient population with enormous unmet need."

In February 2016, durvalumab received Breakthrough Therapy Designation by the US Food and Drug Administration as a potential treatment for patients with PD-L1 positive inoperable or metastatic UBC.2 Durvalumab is also being studied as monotherapy or in combination with tremelimumab, in non-small cell lung cancer (NSCLC), head and neck, bladder, gastric, pancreatic, hepatocellular carcinoma (HCC) and blood cancers, and is a pillar of AstraZeneca's late-stage immuno-oncology program comprising more than 7,000 patients in 19 clinical trials across tumor types.3

*PD-L1-high expression is defined as 25% or more PD-L1 staining in tumor cells (TCs) or immune cells (ICs) as assessed through use of the Ventana SP263 diagnostic assay.1

NOTES TO EDITORS

About Durvalumab

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1).4 PD-L1 expression enables tumors to evade detection from the immune system through binding to PD-1 on cytotoxic T lymphocytes.4,5 Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T cells, countering the tumor's immune- evading tactics.4 Durvalumab is being developed alongside other immunotherapies to activate the patient's immune system to attack the cancer. Durvalumab is being investigated in an extensive clinical trial program, as monotherapy or in combination with tremelimumab, in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers.3 In 2015, durvalumab received Fast Track Designation for the treatment of patients with PD-L1-positive metastatic SCCHN,6 and in 2016, durvalumab was granted Breakthrough Therapy Designation by the US Food and Drug Administration as a potential treatment for metastatic urothelial bladder cancer.2

AstraZeneca's Approach to Immuno-Oncology (IO)

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body's immune system to destroy tumors. At AstraZeneca, and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumor immune suppression, including our anti-PD-L1 antibody, durvalumab, and our anti-CTLA-4 antibody, tremelimumab. We believe that IO-based therapies will offer the potential for life-changing anti-cancer treatments for the vast majority of patients.

We are pursuing a comprehensive clinical trial program that includes durvalumab (anti-PD-L1) monotherapy and durvalumab in combination with tremelimumab (anti-CTLA-4) in multiple tumor 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 partners, may provide new treatment options across a broad range of tumors.

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 repair 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, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas — respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology — as well as in infection and neuroscience. 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.

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 commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including oncology; respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; 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.

REFERENCES

1 Massard C et al. Safety and Efficacy of Durvalumab (MEDI4736), an Anti-PD-L1 Immune Checkpoint Inhibitor, in Patients with Advanced Urothelial Bladder Cancer. JCO Accepted Manuscript. To be published June 2016.

2 AstraZeneca. Durvalumab granted Breakthrough Therapy Designation by US FDA for treatment of patients with PD-L1 positive urothelial bladder cancer. 17 February 2016. Available at https://www.astrazeneca.com/media-centre/press-releases/2016/Durvalumab-granted-Breakthrough-Therapy-designation-by-US-FDA-for-treatment-of-patients-with-PD-L1-positive-urothelial-bladder-cancer-17022016.html. Accessed May 2016.

3 AstraZeneca. Data on File. Q1 2016 Immuno-oncology Update: Clinical Trials Appendix. 2016

4 Stewart R et al. Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1 Monoclonal Antibody. Cancer Immunol Res; 2015. Published OnlineFirst May 5, 2015; doi: 10.1158/2326-6066

5 Patel SP and R Kurzrock. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther2015;14:847-856. Published OnlineFirst February 18, 2015.

6 AstraZeneca. AstraZeneca reports top-line result of tremelimumab monotherapy trial in mesothelioma. 29 February 2016. Available at https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-reports-top-line-result-of-tremelimumab-monotherapy-trial-in-mesothelioma-29022016.html. Accessed May 2016.

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Michele Meixell, +1-302-885-2677

Source: AstraZeneca

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