Updated durvalumab monotherapy data confirm results in urothelial bladder cancer

Updated Study 1108 data presented at ASCO GU demonstrate compelling clinical activity in patients that had previously progressed during or after one line of standard platinum-based chemotherapy

17 February 2017

AstraZeneca and its global biologics research and development arm, MedImmune, today announced updated efficacy and safety data for durvalumab in patients with locally-advanced or metastatic urothelial cancer (UC).

Updated results from the Phase I/II trial, presented at the 2017 ASCO Genitourinary Cancers Symposium, showed an objective response rate (ORR) of 20.4% in all evaluable patients (n=103) (95% confidence interval (CI): 13.1%, 29.5%) and 31.1% (95% CI: 19.9%, 44.3%) in patients whose tumours express PD-L1*. At the time of data cut-off, median overall survival (OS) was 14.1 months (95% CI: 4.7, not estimable).

David Berman, Senior Vice President, Head of Oncology Innovative Medicines at MedImmune, said: “The durable responses observed in this larger data set from Study 1108 confirm the promising efficacy we’ve already seen for durvalumab in patients with advanced bladder cancer. We are continuing to test durvalumab in combination with tremelimumab and as monotherapy in the bladder cancer 1st-line setting in our ongoing Phase III DANUBE trial.”

Durvalumab 10mg/kg was administered intravenously every two weeks for up to 12 months, and demonstrated a manageable safety profile among all patients (n=191). The most common adverse events (AEs) reported in 5% or more of patients were fatigue (19.4%), decreased appetite (9.4%), diarrhoea (8.4%), rash (7.3%), nausea (6.8%), arthralgia (5.8%), pyrexia (5.8%) and pruritus (5.2%). Grade 3 or 4 adverse events occurred in 6.8% of patients, and three patients discontinued treatment due to AEs.

Professor Thomas Powles, Director of Barts Cancer Centre, London, UK, said: “The clinical efficacy of durvalumab in patients with advanced UC is particularly encouraging. For the past three decades we’ve seen limited progress in therapy for bladder cancer patients, and there remains significant unmet need for new treatment options.”

In December 2016, AstraZeneca received FDA acceptance of review of the Biologics License Application (BLA) for durvalumab in patients with locally-advanced or metastatic urothelial carcinoma, whose disease has progressed during or after one standard platinum-based regimen and was granted Priority Review. The urothelial cancer cohort from Study 1108 formed the basis for the BLA submission, which follows the FDA’s Breakthrough Therapy Designation for durvalumab for the treatment of patients with PD-L1 positive inoperable or metastatic urothelial bladder cancer whose tumour has progressed during or after one standard platinum-based regimen.

The combination of durvalumab and tremelimumab is also being studied in non-small cell lung cancer, head and neck squamous cell carcinoma, gastric cancer, pancreatic cancer, hepatocellular carcinoma and haematological malignancies. AstraZeneca currently has more than 30 ongoing durvalumab clinical trials in combination with other IO agents and targeted therapies.

NOTES TO EDITORS

*PD-L1 expression was defined as 25% or more PD-L1 staining in tumour cells (TCs) or immune cells (ICs) as assessed through use of the Ventana^® SP263 PD-L1 Assay.

About durvalumab

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.

Durvalumab is also being studied in the first line treatment of patients with unresectable and metastatic bladder cancer as a monotherapy and in combination with tremelimumab, a checkpoint inhibitor that targets CTLA-4, as part of the DANUBE Phase III trial, which enrolled its first patient during the final quarter of 2015. Additional clinical trials are ongoing to investigate durvalumab as monotherapy or in combination with tremelimumab in non-small cell lung cancer, head and neck squamous cell carcinoma, bladder, gastric, pancreatic, hepatocellular carcinoma and blood cancers.

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 across multiple tumour types.

We are pursuing a comprehensive clinical trial programme that includes durvalumab (PD-L1) monotherapy and durvalumab in combination with tremelimumab (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 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 haematology.

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 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.com and follow us on Twitter @AstraZeneca.

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