a2559c
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 February 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
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Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu improves PFS and OS in HER2-low BC
This announcement contains inside information
21 February 2022 07:00 GMT
Enhertu significantly improved both progression-free
and overall survival in DESTINY-Breast04 trial in patients with
HER2-low metastatic breast cancer
First HER2-low metastatic breast cancer Phase III results for
AstraZeneca and Daiichi Sankyo's Enhertu offer potential to
redefine how the disease is classified and treated
Positive high-level results from the pivotal DESTINY-Breast04 Phase
III trial showed Enhertu (trastuzumab
deruxtecan) demonstrated a statistically significant and clinically
meaningful improvement in both progression-free survival (PFS) and
overall survival (OS) in patients with HER2-low unresectable and/or
metastatic breast cancer regardless of hormone receptor (HR) status
versus physician's choice of chemotherapy.
Enhertu is a HER2-directed
antibody drug conjugate (ADC) being jointly developed by
AstraZeneca and Daiichi Sankyo.
All patients in the trial received a HER2 test, and the results
were centrally confirmed. HER2-low status was defined as an
immunohistochemistry (IHC) score of 1+ or IHC 2+ with a negative
in-situ hybridisation (ISH) score.
Up to 55% of all patients with breast cancer have tumours with a
HER2 IHC score of 1+, or 2+ in combination with a negative ISH
test, a level of HER2 expression not currently eligible for
HER2-targeted therapy.1,2 HER2-low
expression occurs in both HR-positive and HR-negative
disease.3
HER2 testing is well established to determine an appropriate
treatment strategy in metastatic breast cancer. Targeting the lower
range of HER2 expression may offer another approach to delay
disease progression and extend survival in patients with
metastatic breast cancer.4 Currently,
chemotherapy remains the only treatment option both for patients
with HR-positive tumours following progression on endocrine
(hormone) therapy, and for those who are
HR-negative.5
DESTINY-Breast04 met its primary endpoint,
where Enhertu demonstrated superior PFS in previously
treated patients with HR-positive HER2-low metastatic breast cancer
compared to the standard-of-care chemotherapy. The trial met the
key secondary endpoint of PFS in patients with HER2-low metastatic
breast cancer regardless of HR status (HR-positive or HR-negative).
The trial also met the key secondary endpoints of OS in patients
with HR-positive disease and in patients regardless of HR status at
interim analysis.
The safety profile of Enhertu was consistent with previous clinical
trials, with no new safety concerns identified. Overall
interstitial lung disease (ILD) rates were consistent with that
observed in late-line HER2-positive breast cancer trials
of Enhertu, with a lower rate of Grade 5 ILD observed as
determined by an independent adjudication
committee.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca said: "Today's historic news from DESTINY-Breast04
could reshape how breast cancer is classified and treated. A
HER2-directed therapy has never-before shown a benefit in patients
with HER2-low metastatic breast cancer. These results
for Enhertu are a huge step forward and could
potentially expand our ability to target the full spectrum of HER2
expression, validating the need to change the way we categorise and
treat breast cancer."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo said:
"Enhertu continues to redefine the treatment of
HER2-targetable cancers. DESTINY-Breast04 is the first ever Phase
III trial of a HER2-directed therapy in patients with HER2-low
metastatic breast cancer to show statistically significant and
clinically meaningful benefit in progression-free and overall
survival compared to standard treatment. We look forward to sharing
the detailed findings of DESTINY-Breast04 with the medical
community and initiating discussions with regulatory agencies
globally with the goal of bringing Enhertu to patients with metastatic breast cancer
previously considered to be
HER2-negative."
The data will be presented at a forthcoming medical meeting and
shared with global health authorities.
Enhertu (5.4mg/kg) is
approved in more than 40 countries 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
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.
Notes
Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading
causes of cancer-related deaths worldwide.6 More
than two million cases of breast cancer were diagnosed in 2020
resulting in nearly 685,000 deaths globally.6
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, and is one of many biomarkers
expressed in breast cancer tumours.7 HER2
expression is currently defined as either positive or negative, and
is determined by an IHC test which measures the amount of HER2
protein in a cancer cell, and/or an ISH test which counts the
copies of the HER2 gene in cancer cells.7,8 HER2-positive
cancers are defined as IHC 3+ or IHC 2+/ISH+, and HER2-negative
cancers are currently defined as IHC 0, IHC 1+ or IHC
2+/ISH-.7
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label,
registrational Phase III trial evaluating the efficacy and safety
of Enhertu (5.4
mg/kg) versus physician's choice of chemotherapy (capecitabine,
eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients
with HR-positive (n=480) or HR-negative (n=60) HER2-low
unresectable and/or metastatic breast cancer previously treated
with one or two prior lines of chemotherapy. Patients were
randomised 2:1 to receive either Enhertu or
chemotherapy.
The primary endpoint of DESTINY-Breast04 is PFS in patients with
HR-positive disease based on blinded independent central review
(BICR). Key secondary endpoints include PFS based on BICR in all
randomised patients (regardless of HR status), OS in patients with
HR-positive disease and OS in all randomised patients (regardless
of HR status). Other secondary endpoints include PFS based on BICR
and investigator assessment, duration of response based on BICR and
safety.
DESTINY-Breast04 enrolled approximately 540 patients at multiple
sites in Asia, Europe and North 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 more than 40 countries 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
based on the results from the DESTINY-Breast01
trial.
Enhertu (6.4mg/kg) is
approved in several countries for the treatment of adult patients
with locally advanced or metastatic HER2-positive gastric or
gastroesophageal junction (GEJ) 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.
Regulatory applications for Enhertu are currently under review in Europe, Japan,
the US and several other countries for the treatment of adult
patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2-based regimen based on
the results from the DESTINY-Breast03 trial.
Enhertu also is currently
under review in Europe for the treatment of adult patients with
locally advanced or metastatic HER2-positive gastric or GEJ
adenocarcinoma who have received a prior anti-HER2 based regimen
based on the DESTINY-Gastric01 and DESTINY-Gastric02
trials.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (referred to as 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
selective oestrogen receptor degrader (SERD) and potential new
medicine camizestrant.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option
for metastatic breast cancer patients with an inherited BRCA
mutation. Lynparza has also demonstrated a statistically
significant and clinically meaningful improvement in invasive
disease-free survival versus placebo in the adjuvant treatment of
patients with germline BRCA-mutated HER2-negative early breast
cancer. 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, 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, evaluating 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. Tarantino P, et al. HER2-Low Breast Cancer: Pathological and
Clinical Landscape. J Clin
Oncol. 2020;38(17):1951-1962.
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. Miglietta F, et al. Evolution of HER2-low expression from
primary to recurrent breast cancer. NPJ Breast Cancer. 2021; 7:137;
10.1038/s41523-021-00343-4.
4. Eiger D, et al. The Exciting New Field of HER2-Low Breast
Cancer Treatment. Cancers. 2021;
10.3390/cancers13051015.
5. Matutino A, et al. Hormone receptor-positive, HER2-negative
metastatic breast cancer: redrawing the lines. Current Oncology.
2018; 25(S1):S131-S141.
6. 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.
7. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
8. Wolff A, et al. Human Epidermal Growth Factor Receptor 2 Testing
in Breast Cancer: American Society of Clinical Oncology/College of
American Pathologists Clinical Practice Guideline Focused
Update. Arch Pathol Lab
Med. 2018; 142 (11):
1364-1382.
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:
21 February 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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