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 August 2021
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.
Enhertu
head-to-head trial meets primary endpoint
9 August 2021 07:00 BST
Enhertu significantly
improved progression-free survival
in DESTINY-Breast03 head-to-head
trial vs. trastuzumab emtansine (T-DM1) in patients with
HER2-positive metastatic breast cancer
IDMC recommended unblinding based on primary efficacy
endpoint demonstrating superiority; results also indicate
strong trend toward improved overall survival
Plans for global regulatory submissions underway
Positive high-level results from the head-to-head DESTINY-Breast03
Phase III trial showed that Enhertu (trastuzumab deruxtecan), the AstraZeneca
and Daiichi Sankyo Company, Limited (Daiichi Sankyo) HER2-directed
antibody drug conjugate (ADC), demonstrated superiority over
trastuzumab emtansine (T-DM1).
At a planned interim analysis, the Independent Data Monitoring
Committee (IDMC) concluded that DESTINY-Breast03 met the primary
endpoint of progression-free survival (PFS) showing a
highly statistically significant and clinically meaningful
improvement for patients with HER2-positive, unresectable
and/or metastatic breast cancer previously treated with trastuzumab
and a taxane.
In DESTINY-Breast03, Enhertu also showed a strong trend toward improved
overall survival (OS) compared to T-DM1 in a key secondary
endpoint, although the OS data are still immature. The safety
profile of Enhertu was consistent with previous clinical
trials, with no new safety concerns identified and no Grade 4 or 5
treatment-related interstitial lung disease
events.
Susan Galbraith, Executive Vice President, Oncology R&D, said:
"There is a continued need for new options and better outcomes for
patients with HER2-positive metastatic breast cancer who often
experience disease progression after initial treatment with
available standards of care. These transformative progression-free
survival results demonstrate the superiority
of Enhertu compared to T-DM1, and the encouraging
safety data may open future opportunities to bring this benefit to
patients in earlier treatment settings."
Ken Takeshita, Global Head, Research and Development, Daiichi
Sankyo, said: "DESTINY-Breast03 is the first global Phase III
head-to-head trial of Enhertu against an active control and supports the
potential of this medicine to become the new standard of care for
patients with HER2-positive metastatic breast cancer following
initial treatment with trastuzumab and a taxane. We believe
this highly sophisticated and specifically engineered ADC is
fulfilling its promise to reshape the treatment of HER2-positive
metastatic breast cancer, with the goal to move into earlier lines
of treatment for HER2-positive breast cancer and many other
HER2-expressing tumour types across our broad clinical trial
programme."
The data will be presented at an upcoming medical meeting and
shared with health authorities.
Enhertu is approved for
the treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received two or more prior
anti-HER2-based regimens in the metastatic setting in the US,
Japan, the EU and several other countries based on the results from
the DESTINY-Breast01 trial.
Enhertu is being further
assessed in a comprehensive clinical development
programme evaluating efficacy and safety across multiple
HER2-targetable cancers, including breast, gastric, lung and
colorectal cancers.
HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the
leading causes of cancer-related deaths in women
worldwide.1 More
than two million patients with breast cancer were diagnosed in
2020, resulting in nearly 685,000 deaths
globally.1 Approximately
one in five patients with breast cancer are considered
HER2-positive.2
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including
breast, gastric, lung and colorectal cancers.3 HER2
protein overexpression may occur as a result of HER2 gene
amplification and is often associated with aggressive disease and a
poor prognosis in breast cancer.4
Despite initial treatment with trastuzumab and a taxane, patients
with HER2-positive metastatic breast cancer will often experience
disease progression.5 More
effective options are needed to further delay progression and
extend survival.5-7
DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label,
registrational Phase III trial evaluating the safety and efficacy
of Enhertu (5.4mg/kg) versus T-DM1 in patients with
HER2-positive unresectable and/or metastatic breast cancer
previously treated with trastuzumab and a taxane. The primary
efficacy endpoint of DESTINY-Breast03 is PFS based on blinded
independent central review. Secondary efficacy endpoints include
OS, objective response rate, duration of response, clinical benefit
rate, PFS based on investigator assessment and
safety.
DESTINY-Breast03 enrolled approximately 500 patients at
multiple sites in Asia, Europe, North America, Oceania and South
America. For more information about the trial,
visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed
ADC. Designed using Daiichi Sankyo's proprietary DXd ADC
technology, Enhertu is the lead ADC in the oncology portfolio of
Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC
scientific platform. Enhertu consists of a HER2 monoclonal antibody
attached to a topoisomerase I inhibitor payload, an exatecan
derivative, via a stable tetrapeptide-based cleavable
linker.
Enhertu (5.4mg/kg) is
approved in Canada, the EU, Israel, Japan, the UK and the US for
the treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received two or more prior
anti-HER2-based regimens in the metastatic setting based on the
results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is also
approved in Israel, Japan and the US for the treatment of adult
patients with locally advanced or metastatic HER2-positive gastric
or gastroesophageal junction adenocarcinoma who have received a
prior trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 trial.
Enhertu development programme
A comprehensive development programme is underway globally,
evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal cancers.
Trials in combination with other anticancer treatments, such as
immunotherapy, are also underway.
Enhertu was highlighted in
the Clinical Cancer Advances 2021 report as one of two significant
advancements in the "ASCO Clinical Advance of the Year: Molecular
Profiling Driving Progress in GI Cancers," based on data from both
the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of
the targeted therapy advances of the year in non-small cell lung
cancer (NSCLC), based on the interim results of the HER2-mutated
cohort of the DESTINY-Lung01 trial.
In May 2020, Enhertu also received Breakthrough Therapy
Designation for the treatment of patients with metastatic NSCLC
whose tumours have a HER2-mutation and with disease progression on
or after platinum-based therapy.
Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration
to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and
datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July
2020, except in Japan where Daiichi Sankyo maintains exclusive
rights. Daiichi Sankyo is responsible for manufacturing and supply
of Enhertu and datopotamab
deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge, and redefine, the current
clinical paradigm for how breast cancer is classified and treated
to deliver even more effective treatments to patients in need -
with the bold ambition to one day eliminate breast cancer as a
cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising
compounds in development that leverage different mechanisms of
action to address the biologically diverse breast cancer tumour
environment. AstraZeneca aims to continue to transform outcomes for
HR-positive breast cancer with foundational
medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral
SERD and potential new medicine AZD9833.
PARP inhibitor, Lynparza (olaparib) is a targeted treatment option
for metastatic breast cancer patients with an inherited BRCA
mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and
Canada) continue to research Lynparza in metastatic breast cancer patients with an
inherited BRCA mutation and are exploring new opportunities to
treat these patients earlier in their disease.
Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated
HER2-positive metastatic breast cancer, AstraZeneca and Daiichi
Sankyo are exploring its potential in earlier lines of treatment
and in new breast cancer settings. To bring much needed treatment
options to patients with triple-negative breast cancer, an
aggressive form of breast cancer, AstraZeneca is testing
immunotherapy Imfinzi (durvalumab) in combination with other
oncology medicines, including Lynparza and Enhertu, investigating the potential of AKT kinase
inhibitor, capivasertib, in combination with chemotherapy, and
collaborating with Daiichi Sankyo to explore the potential of
TROP2-directed ADC, datopotamab deruxtecan.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition
to provide cures for cancer in every form, following the science to
understand cancer and all its complexities to discover, develop and
deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It
is through persistent innovation that AstraZeneca has built one of
the most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, 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.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1.
Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in
185 Countries. CA Cancer J
Clin. 2021;
10.3322/caac.21660.
2.
Ahn S, et al. HER2 status in breast cancer: changes in
guidelines and complicating factors for
interpretation. J Pathol Transl
Med. 2020; 54(1):
34-44.
3.
Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
4.
Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report
from the Lung Cancer Mutation Consortium. Cancer. 2017;1;123(21):4099-4105.
5.
Barok M, et al. Trastuzumab emtansine: mechanism of action and
drug resistance. Breast Cancer
Res. 2014;
16(2):209.
6.
Mounsey L, et al. Changing Natural History of HER2-Positive Breast
Cancer Metastatic to the Brain in the Era of New Targeted
Therapies. Clin Breast
Cancer. 2018;
18(1):29-37.
7.
Martinez-S Sáez O, et al. Current and Future Management of HER2-Positive
Metastatic Breast Cancer. JCO Oncol
Pract. 2021.
10.1200/OP.21.00172.
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: 9
August 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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