AstraZeneca Commences First Ever Phase II Randomised Study of a Src Inhibitor in Ovarian Cancer

- Commitment to Ovarian Cancer Treatment Reinforced

- For Non-US and Non-UK Healthcare Professional Press Only

ALDERLEY PARK, England, 6 May 2008

AstraZeneca today announced the start of the first ever Phase

II randomised study investigating a selective Src inhibitor in treating

advanced ovarian cancer, following enrolment of the first patient to OVERT-1.

OVERT (OVarian Cancer Evaluation and Response to Src

Inhibition Therapy)-1 will seek to determine if the selective Src inhibitor,

AZD0530, can improve the efficacy of traditional chemotherapy for the

treatment of advanced ovarian cancer recurrent after standard therapy. It

will measure the objective tumour response rate and time to disease

progression in patients treated with AZD0530 in combination with carboplatin

plus paclitaxel in relation to those treated with carboplatin plus paclitaxel

alone.

AZD0530 is a once daily, oral, potent, selective Src inhibitor

that modulates multiple key signalling pathways in cancer. This

investigational compound is now in Phase II clinical development in a number

of cancer settings. It is the first agent to have demonstrated statistically

significant inhibition of Src in human tumour tissue.(1) Preclinical studies

identified AZD0530 as a selective inhibitor of Src activity and biomarker

study data presented at ASCO in 2007 confirmed inhibition of Src in human

cancers.(2)

Src was the first cancer-causing gene to be identified,

following research in the 1970s. The Src oncogene was then identified as a

key genetic component of the Rous Sarcoma Virus, itself discovered by Nobel

Prizewinner Dr Peyton Rous in 1910.(3) As the protein products of Src and

related oncogenes, Src kinases are a family of molecules that play an

important role in cancer growth and spread. By inhibiting Src, it is hoped

that cancer progression may be delayed.

Src is important in the pathogenesis of ovarian cancer.(4)

Despite over 30 years of research since its identification, OVERT-1 is the

first Phase II randomised study to investigate the clinical efficacy of a Src

inhibitor in ovarian cancer.

The OVERT-1 study reinforces AstraZeneca's commitment to

patients with ovarian cancer, the fifth leading cause of cancer-related

deaths in women aged 35 - 74 years.(5) Other commitments include the ongoing

ICEBERG (International Collaborative Expertise for BRCA Education and

Research through Genetics) studies, which seek to evaluate the ability of

AZD2281 (KU-0059436), a PARP (Poly-ADP-Ribose Polymerase) inhibitor, to treat

women with BRCA1 or BRCA2 positive ovarian cancer or breast cancer.

Principal Investigator of the OVERT-1 study, Professor

Christopher Poole, Medical Oncologist at the University of Warwick, UK, said:

"AZD0530 has the promise to target a wide range of tumours and the potential

to benefit patients with both early and advanced cancers.

"It has a ‘multi-mechanistic’ mode of action, meaning it has

both the potential to delay the recurrence and spread of tumours and to

enhance the efficacy of many standard cancer therapies.

"In the OVERT-1 study, we hope to investigate the activity of

AZD0530 in patients with recurrent advanced ovarian cancer whose tumours may

still retain some useful sensitivity to standard chemotherapy and to whom we

would ordinarily offer treatment with conventional drugs.

"The purpose of the study is to see if AZD0530 will add to

their benefits, generating better than expected response rates and more

durable remissions. I share a real sense of excitement about this project."

Notes to Editors:

Study Details: Phase II, double-blind, placebo-controlled,

multi-centre, randomised study of AZD0530 in patients with advanced ovarian

cancer sensitive to platinum-based chemotherapy. Up to 200 patients will be

enrolled:

Inclusion criteria: diagnosis of advanced ovarian cancer,

evidence of recurrence or disease progression, estimated life expectancy of

more than 12 weeks. Previous response to platinum-based chemotherapy.

Exclusion criteria: Central Nervous System (CNS) metastases,

inadequate bone marrow reserve, inadequate liver function, renal function or

low haemoglobin, pregnant, breastfeeding or if of child-bearing status

unwilling to use acceptable method of contraception.

AstraZeneca is a major international healthcare business engaged in

research, development, manufacturing and marketing of prescription

pharmaceuticals and supplier for healthcare services. AstraZeneca is one of

the world's leading pharmaceutical companies with healthcare sales of

US$29.55 billion and is a leader in gastrointestinal, cardiovascular,

neuroscience, respiratory, oncology and infection product sales. AstraZeneca

is listed in the Dow Jones Sustainability Index (Global) as well as the

FTSE4Good Index.

Reference List

(1) Green, T.P. et al. First demonstration of the inhibition of Src

signalling in tumour tissue in humans using the Src inhibitor AZD0530.

Presented at AACR 15 April, 2008.

(2) Phase I study of AZD0530, an oral potent inhibitor of Src Kinase:

first demonstration of inhibition of Src activity in human cancers, presented

at oral session at ASCO 2007.

(3) From the Archive: Peyton Rous, Father of the Tumour Virus. Journal of

Experimental Medicine, Vol 201, 3, p320-320, 2005

(4) Early Events in the Pathogenesis of Epithelial Ovarian Cancer. Landen

CN, Birrer MJ, Sood AK. Journal of Clinical Oncology 2008: 26; 995-1005.

(5) National Ovarian Cancer Coalition Inc.

For further information, please contact:

Helen Wailes

Helen.Wailes@astrazeneca.com

Tel: +44(0)1625-510975