Fourth Phase III Study of Vandetanib (ZACTIMA(TM), ZD6474) in Patients With Advanced Lung Cancer

Fourth Phase III Study of Vandetanib (ZACTIMA(TM), ZD6474) in Patients With Advanced Lung Cancer

February 26, 2007

A Phase III international, parallel group, randomised,
double-blind study of vandetanib in combination with
pemetrexed for advanced non-small cell lung cancer (NSCLC)
after failure of first line anti-cancer therapy

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


    ALDERLEY PARK, Cheshire, Feb. 26 /Xinhua-PRNewswire/ --
AstraZeneca today announced that a new Phase III study of
novel once-daily oral anti-cancer drug, vandetanib
(ZACTIMA(TM), ZD6474), is underway. The study - Study 36 -
will investigate the addition of vandetanib to pemetrexed
(Alimta(R)) as second line treatment for patients with
locally advanced or metastatic non-small cell lung cancer
(NSCLC) after failure of first line anti-cancer treatment.
Study 36 will be conducted across 20 countries worldwide,
and is expected to enrol at least 508 patients.

    As its primary objective, Study 36 will evaluate
progression-free survival with vandetanib 100mg plus
pemetrexed 500mg/m2 compared with pemetrexed 500mg/m2 plus
placebo in patients with advanced NSCLC, who have
previously received anti-cancer treatment. The study will
also assess overall survival, objective response rate,
disease control rate, duration of response, effect on
disease related symptoms, time to deterioration of
disease-related symptoms, the safety and tolerability of
vandetanib in combination with pemetrexed, and population
pharmacokinetics of vandetanib

    Study 36's Principal Investigator, Dr. Richard de Boer,
Western Hospital, Victoria, Australia, commented "After
treatment failure with initial therapy, response rates to
further treatment is low in patients with advanced
non-small cell lung cancer. The effect of combining novel
targeted agents such as vandetanib with chemotherapy needs
to be explored to progress treatment options for patient
benefit."

    Study 36 forms part of an extensive ongoing clinical
development programme for vandetanib in NSCLC and is the
fourth Phase III study in this tumour; the other three
studies are:

    -- Study 32 - a randomised, double-blind study,
comparing
       vandetanib 100mg in combination with docetaxel with
docetaxel alone in
       patients with locally advanced or metastatic NSCLC
after failure of
       first-line treatment.

    -- Study 57 - a randomised, double-blind, study of
vandetanib 300mg
       monotherapy versus erlotinib 150mg in patients with
advanced NSCLC     
       after failure of at least one, but no more that two,
prior chemotherapy
       regimens.

    -- Study 44 - a randomised, double-blind,
placebo-controlled study
       of vandetanib 300mg plus best supportive care (BSC)
compared with      
       placebo plus BSC as third/fourth line treatment in
patients with non-
       small cell lung cancer (NSCLC) after treatment
failure with  
       chemotherapy and an epidermal growth factor receptor
tyrosine kinase 
       inhibitor (EGFR TKI).

    Vandetanib (ZACTIMA(TM), ZD6474)

    Vandetanib works by inhibiting both the development of
the tumour's blood supply through inhibition of VEGFR
(anti-angiogenesis) and the growth and survival of the
tumour itself through inhibition of EGFR. It also inhibits
RET kinase, an important growth factor in certain types of
thyroid cancer. Vandetanib has shown promising anti-tumour
activity in NSCLC when used alone and in combination with
docetaxel in Phase II trials.(1,2) It has also shown
encouraging early data in hereditary medullary thyroid
cancer(3) and has been awarded FDA and EU orphan drug
status, and FDA fast track designation for this indication.
Vandetanib is currently in clinical development in a range
of tumours.

    ZACTIMA(TM) is a trademark of the AstraZeneca group of
companies.

    Notes to editors

    -- Over 1.35 million new cases of lung cancer are
diagnosed every year and nearly 1.2 million people die as a
result of this devastating disease - more than breast, colon
and prostate cancer combined.(4)

    -- If lung cancer is detected at early stages, before
it has spread to other organs or lymph nodes, around half
of patients can survive for five years or more. However,
few lung cancers are found at this early stage and it is
normally diagnosed at the advanced stage, when five year
survival falls to approximately 15%.(5)

    -- AstraZeneca is a major international healthcare
business engaged in the research, development, manufacture
and marketing of prescription pharmaceuticals and the
supply of healthcare services. It is one of the world's
leading pharmaceutical companies with healthcare sales of
US$26.47 billion and leading positions in sales of
gastrointestinal, cardiovascular, neuroscience,
respiratory, oncology and infection products. AstraZeneca
is listed in the Dow Jones Sustainability Index (Global) as
well as the FTSE4 Good Index.

    -- For more information about AstraZeneca, please
visit: http://www.astrazeneca.com .

    References

    (1) Natale RB et al. ZD6474 versus gefitinib in
patients with advanced
        NSCLC: Final results from a two-part, double-blind
randomized phase II
        trial. Proceedings of ASCO 2006; abstract no.
7000.

    (2) Heymach JV et al. A phase II trial of ZD6474 plus
docetaxel in
        patients with previously treated NSCLC: Follow-up
results. Proceedings
        of ASCO 2006; abstract no. 7016.

    (3) Wells S et al. A phase II trial of ZD6474 in
patients with hereditary
        metastatic medullary thyroid cancer. Proceedings of
ASCO; abstract 
        no. 5533.

    (4) Ferlay J et al. GLOBOCAN 2002: Cancer Incidence,
Mortality and
        Prevalence Worldwide IARC CancerBase No. 5. version
2.0, IARCPress,  
        Lyon, 2004.

    (5) Bepler G. Lung cancer epidemiology and genetics.
Journal of Thoracic
        Imaging 1999;14(4):228-34.


    For more information, please contact:

     Janet Milton-Edwards
     AstraZeneca
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]

     Carrie Deverell
     AstraZeneca
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]


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