FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of May
2019
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Trastuzumab
deruxtecan demonstrated clinically
8 May 2019 07:00
BST
Trastuzumab deruxtecan demonstrated clinically-meaningful response
in
patients with refractory HER2-positive metastatic breast cancer, a
population with high unmet need
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 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 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 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 and
follow us on Twitter@AstraZeneca.
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Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
08 May
2019
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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