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2019-05-08

AstraZeneca: Trastuzumab deruxtecan demonstrated clinically-meaningful response in patients with refractory HER2-positive m...

Pivotal Phase II DESTINY-Breast01 trial met primary endpoint,
supporting global regulatory submission plan to start in H2 2019

AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) today
announced positive top-line results for the pivotal Phase II
DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201). The
HER2-targeting antibody drug conjugate (ADC) and potential new
medicine was evaluated in patients with HER2-positive, unresectable
and/or metastatic breast cancer previously treated with trastuzumab
emtansine.

The response rate in DESTINY-Breast01, as assessed by an independent
review committee, confirms in a heavily-pretreated, global patient
population the unprecedented clinical activity in the
recently-published
(https://www.astrazeneca.com/media-centre/medical-releases/astrazeneca-an...)
Phase I trial. The safety and tolerability profile of trastuzumab
deruxtecan was also consistent with previous experience. These
results are expected to support planned global regulatory
submissions, including a Biologics License Application with the US
Food and Drug Administration (FDA) anticipated in the second half of
2019.

DESTINY-Breast01 is a pivotal Phase II, open-label, global,
multicentre, two-part trial of trastuzumab deruxtecan. The optimal
dose of 5.4mg/kg was previously identified in part one of the trial.
Today's results from part two evaluated the efficacy and safety of
that dose in patients who have failed or discontinued previous
treatment with trastuzumab emtansine.

José Baselga, Executive Vice President, R&D Oncology, said: "We are
encouraged to see positive data from trastuzumab deruxtecan, with the
DESTINY-Breast01 trial now reinforcing what earlier data have shown.
We believe this antibody drug conjugate has the potential to redefine
the treatment of patients with HER2-expressing cancers, and we are
eager to bring it as quickly as possible to patients with refractory
HER2-positive breast cancer who continue to have high unmet medical
need."

Antoine Yver, MD, MSc, Executive Vice President and Global Head,
Oncology Research and Development, Daiichi Sankyo, said: "These
results confirm our commitment to pursue accelerated regulatory
pathways in HER2-positive metastatic breast cancer with trastuzumab
deruxtecan. We are more dedicated than ever to our comprehensive and
ambitious development strategy evaluating the potential across a
spectrum of HER2-expressing cancers including breast, gastric, lung
and colorectal."

Trastuzumab deruxtecan has been granted US FDA Breakthrough Therapy
Designation and Fast Track Designation for HER2-positive patients in
the advanced or refractory breast cancer setting. A recent
publication
(https://www.astrazeneca.com/media-centre/medical-releases/astrazeneca-an...)
in The Lancet Oncology reported long-term Phase I safety and
preliminary efficacy results in HER2-positive metastatic breast
cancer. This potential new medicine is currently in development for
the treatment of multiple HER2-expressing cancers, including in
patients with HER2-low expression.

AstraZeneca and Daiichi Sankyo plan to present the data from
DESTINY-Breast01 at a forthcoming medical meeting.

About HER2

HER2 is a tyrosine kinase receptor growth-promoting protein found on
the surface of some cancer cells that is associated with aggressive
disease and poorer prognosis in breast cancer patients. To be
considered HER2-positive, tumour cancer cells are usually tested by
one of two methods: immunohistochemistry (IHC) or fluorescent in situ
hybridization (FISH). IHC test results are reported as: 0, IHC 1+,
IHC 2+, or IHC 3+. A finding of IHC 3+ and/or FISH amplification is
considered positive. There are currently no targeted therapies for
HER2-FISH-negative, IHC 2+ or IHC 1+ tumours.

Unmet need in HER2-positive breast cancer

Approximately one in five breast cancers are HER2-positive. Several
unmet treatment needs remain today in HER2-positive metastatic breast
cancer. Many HER2-positive breast cancers eventually advance to the
point where no currently-approved HER2-targeting medicine continues
to control the disease; after treatment with trastuzumab, pertuzumab,
and trastuzumab emtansine, optimal treatment is less-clearly defined
and choices may be limited.

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal Phase II, open-label, global,
multicentre, two-part trial evaluating the safety and efficacy of
trastuzumab deruxtecan in patients with HER2-positive unresectable
and/or metastatic breast cancer previously treated with trastuzumab
emtansine. The primary endpoint of the trial is objective response
rate. Secondary objectives include duration of response, disease
control rate, clinical benefit rate, progression-free survival and
overall survival.

The first part of the trial includes a pharmacokinetic stage and a
dose-finding stage to identify the recommended dose of trastuzumab
deruxtecan to be evaluated in the second part of the trial. The
second part enrolled patients into one of two cohorts: patients
resistant or refractory to trastuzumab emtansine (part 2a) and
patients who discontinued treatment with trastuzumab emtansine for
reasons other than resistant or refractory disease (part 2b).
Enrolment into DESTINY-Breast01 was completed in September 2018, with
253 patients at more than 100 sites across North America, Europe,
Japan and other countries in Asia.

The safety and tolerability profile of trastuzumab deruxtecan in
DESTINY-Breast01 was consistent with the recently-published
(https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30097-X/fulltext)
Phase I trial, in which the most common adverse events (?30%, any
grade) included nausea, decreased appetite, vomiting, alopecia,
fatigue, anaemia, diarrhoea, and constipation. Cases of drug-related
pneumonitis, including grade 5 events, have also been reported in the
clinical development programme.

About trastuzumab deruxtecan

Trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in the
US only) is the lead product in the investigational ADC franchise of
the Daiichi Sankyo Cancer Enterprise and the most-advanced programme
in AstraZeneca's ADC scientific platform. ADCs are targeted cancer
medicines that deliver cytotoxic agents to cancer cells via a linker
attached to a monoclonal antibody that binds to a specific target
expressed on cancer cells.

A broad and comprehensive development programme with trastuzumab
deruxtecan is underway in North America, Europe and Asia, including
five pivotal trials in HER2-expressing breast and gastric cancers,
including in breast cancer patients with HER2-low expression.
Trastuzumab deruxtecan is also in Phase II development for
HER2-expressing advanced colorectal cancer and metastatic
non-squamous HER2-overexpressing or HER2-mutated NSCLC, and Phase I
development in combination with nivolumab for HER2-expressing
metastatic breast and bladder cancers.

Trastuzumab deruxtecan was granted Breakthrough Therapy Designation in
2017 by the US FDA for the treatment of patients with HER2-positive,
locally-advanced or metastatic breast cancer who have been treated
with trastuzumab and pertuzumab and have disease progression after
trastuzumab emtansine. Fast Track Designation was also granted in the
US for the treatment of HER2-positive unresectable and/or metastatic
breast cancer in patients who have progressed after prior treatment
with HER2-targeted medicines, including trastuzumab emtansine.
Trastuzumab deruxtecan has received SAKIGAKE designation for the
treatment of HER2-positive advanced gastric or gastro-oesophageal
junction cancer by the Japan Ministry of Health, Labour and Welfare.

About the collaboration between AstraZeneca and Daiichi Sankyo

In March 2019, AstraZeneca and Daiichi Sankyo entered into a global
collaboration to jointly develop and commercialise trastuzumab
deruxtecan as a medicine worldwide, except in Japan where Daiichi
Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely
responsible for manufacturing and supply.

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 Oncology as a key growth driver for AstraZeneca
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 therapy areas - Oncology, Cardiovascular, Renal & Metabolism
and Respiratory. AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide. For
more information, please visit astrazeneca.com
(http://www.astrazeneca.com/) and follow us on Twitter @AstraZeneca
(https://twitter.com/AstraZeneca).

Media Relations
Gonzalo Viña +44 203 749 5916
Rob Skelding Oncology +44 203 749 5821
Rebecca Einhorn Oncology +1 301 518 4122
Matt Kent BioPharma +44 203 749 5906
Jennifer Hursit Other +44 203 749 5762
Christina Sweden +46 8 552 53 106
Malmberg
Hägerstrand
Michele US +1 302 885 2677
Meixell

Investor
Relations
Thomas Kudsk +44 203 749 5712
Larsen
Henry Wheeler Oncology +44 203 749 5797
Christer BioPharma (cardiovascular, metabolism) +44 203 749 5711
Gruvris
Nick S...

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