Blueprint
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 January
2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
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to the Commission pursuant to Rule 12g3-2(b) under the Securities
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Phase II DESTINY-Gastric01 trial of
Enhertu versus chemotherapy
met primary endpoint
27 January 2020 07:00 GMT
Phase II DESTINY-Gastric01 trial
of Enhertu versus
chemotherapy met primary endpoint
Trial met primary endpoint of objective response rate and key
secondary
endpoint of overall survival in patients with previously treated
HER2-positive metastatic gastric cancer
High-level results from the positive registrational Phase II trial
DESTINY-Gastric01 showed AstraZeneca's and Daiichi Sankyo Company,
Limited (Daiichi Sankyo)'s Enhertu (trastuzumab deruxtecan), achieved a
statistically significant and clinically meaningful improvement in
objective response rate (ORR) and overall survival (OS) in patients
with HER2-positive unresectable or metastatic gastric or
gastroesophageal junction cancer that had progressed following two
or more treatment regimens including trastuzumab and
chemotherapy.
The trial met its primary endpoint of an improvement in ORR, as
assessed by an independent review committee, in patients treated
with Enhertu compared to investigator's choice of
chemotherapy (irinotecan or paclitaxel
monotherapy). Enhertu also showed a statistically significant and
clinically meaningful improvement in OS, a key secondary
endpoint.
José Baselga, Executive Vice President, Oncology R&D,
said: "Gastric cancer is usually diagnosed in the advanced stage
and patients face markedly high mortality rates, making the need
for new therapies especially urgent. Given the previous results
seen in our HER2-positive development programme and now in
HER2-positive metastatic gastric cancer, we believe this
antibody drug conjugate has the potential to redefine the
treatment of patients with HER2-expressing cancers."
Gilles Gallant, Senior Vice President, Global Head, Oncology
Development, Oncology R&D, Daiichi Sankyo, said: "We are
excited to report positive top-line results from this trial. Our
development plan remains on track in gastric cancer, including an
initial regulatory application in Japan where gastric cancer is
highly prevalent, and where SAKIGAKE designation has been granted
for this indication. We are strongly committed to bringing this
therapy as rapidly as possible to patients in need."
The overall safety and tolerability profile
of Enhertu in DESTINY-Gastric01 was consistent with
that seen in the published Phase I trial in which the most common
adverse events (≥30 percent, any grade) were haematologic and
gastrointestinal including neutrophil count decrease, anaemia,
nausea and decreased appetite. There were cases of
treatment-related interstitial lung disease (ILD) and pneumonitis,
the majority of which were Grade 1 and 2 with two Grade 3 and one
Grade 4. No ILD-related deaths (Grade 5) occurred in gastric
patients in the Phase I trial or in the DESTINY-Gastric01
trial.
These results confirm activity seen in the
non-randomised Phase I trial of Enhertu in patients with HER2-positive advanced
gastric cancer published in The
Lancet Oncology.1 Data
from DESTINY-Gastric01 will be presented at a forthcoming medical
meeting.
In addition to the planned discussion with the Japan Ministry of
Health, Labour and Welfare (MHLW), both companies plan to discuss
the data with other health authorities. Enhertu recently received Accelerated Approval
in the US for
HER2-positive unresectable or metastatic breast cancer following
two or more prior anti-HER2 based treatment regimens and additional
global regulatory submissions in HER2-positive metastatic breast
cancer are underway.
Enhertu is being jointly
developed and commercialised worldwide with AstraZeneca except in
Japan where Daiichi Sankyo maintains exclusive
rights.
HER2
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours including
gastric, breast and lung cancers. HER2 overexpression is often
associated with aggressive disease and poorer
prognosis.2 When
a patient is diagnosed with gastric cancer, guidelines recommend
evaluating HER2-expression levels by an immunohistochemistry (IHC)
test.3 A
finding of IHC 3+ is considered positive. A result of IHC 2+ is
considered equivocal, in which case an additional testing method of
in situ hybridisation (ISH) is recommended to confirm HER2
status.
Gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the third leading cause of cancer mortality; there were
approximately one million new cases reported in 2018 and 783,000
deaths.4 Incidence
rates for gastric cancer are markedly higher in eastern Asia, where
approximately half of all cases occur.4 South
Korea and Japan have the first and third highest incidence rates of
gastric cancer worldwide, respectively; in 2018, the
age-standardised rate in Japan was 27.5 per 100,000 and in South
Korea it was 39.6 per 100,000.5
Approximately one in five gastric cancers are HER2
positive.6 Gastric
cancer is usually diagnosed in the advanced stage, but even when
diagnosed in earlier stages of the disease the survival rate
remains modest.7 Recommended
1st-line treatment for HER2-positive advanced or metastatic gastric
cancer is combination chemotherapy plus trastuzumab, an anti-HER2
medicine, which has been shown to improve survival outcomes when
added to chemotherapy.8 For
gastric cancer that progresses on trastuzumab, there are no other
approved HER2-targeting medicines and subsequent treatment options
are limited.9
DESTINY-Gastric01
DESTINY-Gastric01 is a registrational Phase II, open-label,
multi-centre trial assessing the safety and efficacy
of Enhertu in 189 patients from Japan and South Korea
with HER2-expressing advanced gastric cancer or gastroesophageal
junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have
progressed on two or more prior treatment regimens including
fluoropyrimidine (5-FU) and platinum chemotherapy and trastuzumab.
Patients were randomised 2:1 to receive Enhertu or investigator's choice of chemotherapy
(paclitaxel or irinotecan monotherapy). Patients were treated
with Enhertu 6.4mg/kg once every three weeks or
chemotherapy given on the same schedule. The primary endpoint
of the trial is ORR. Secondary endpoints include OS,
progression-free survival, duration of response, disease control
rate and time to treatment failure as well as pharmacokinetic and
safety endpoints.
Enhertu
Enhertu (fam-trastuzumab
deruxtecan-nxki in the US only; trastuzumab deruxtecan outside the
US) is a HER2-directed antibody drug conjugate (ADC) and is the
lead product in the 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 chemotherapy ("payload") to cancer cells via a
linker attached to a monoclonal antibody that binds to a specific
target expressed on cancer cells.
Enhertu clinical
development
A comprehensive development programme is underway globally with
five registrational trials in HER2-expressing metastatic breast and
gastric cancers including a trial in patients with metastatic
breast cancer and low levels of HER2 expression. Phase II trials
are underway for HER2-expressing advanced colorectal cancer, as
well as metastatic non-squamous HER2-overexpressing or HER2-mutated
non-small cell lung cancer. Trials in combination with other
anticancer treatments, such as immunotherapy, are also
underway.
Collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global
collaboration to jointly develop and
commercialise Enhertu worldwide, except in Japan where Daiichi
Sankyo maintains exclusive rights. Daiichi Sankyo is solely
responsible for manufacturing and supply.
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, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
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.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) 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 and Metabolism, and Respiratory.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Media
Relations
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Viña
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Skelding
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Oncology
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+44 203
749 5821
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Rebecca
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+1 301
518 4122
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749 5906
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References
1. Shitara
K et al. Lancet Oncol. 2019; S1470-2045
(19):30088-9.
2.
Iqbal and Iqbal. Mol Biol Int. 2014; 2014: 852748.
3.
NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20,
2019: GAST-B 3.
4.
Bray F et al. GLOBOCAN CA CANCER J CLIN
2018;68:394-424.
5. World Cancer
Research Fund International. Stomach Cancer Statistics. 2018.
Accessed 25 January 2020: https://www.wcrf.org/dietandcancer/cancer-trends/stomach-cancer-statistics.
6. American Cancer Society.
Tests for Stomach Cancer. 2017. Accessed 25 January
2020: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.
7.
Curea et al. Cancer Biotherapy & Radiopharmaceuticals. 2017;32
(10): Review.
8.
NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20,
2019: MS-22.
9.
NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20,
2019: MS-36.
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:
27 January
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|