a4543j
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 April 2022
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
granted BTD for HER2-low breast cancer
27 April 2022 07:00 BST
Enhertu granted
Breakthrough Therapy Designation in the US for patients with
HER2-low metastatic breast cancer
Based on DESTINY-Breast04 results where AstraZeneca and Daiichi
Sankyo's Enhertu demonstrated a significant improvement in both
progression-free survival and overall survival
Enhertu has now been granted five Breakthrough Therapy
Designations, including three in breast cancer and one in both lung
and gastric cancers
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been granted
Breakthrough Therapy Designation (BTD) in the US for the treatment
of adult patients with unresectable or metastatic HER2-low
(IHC 1+ or IHC 2+/ISH-negative) breast cancer who have
received a prior systemic therapy in the metastatic setting or
developed disease recurrence during or within six months of
completing adjuvant chemotherapy. Patients with hormone receptor
(HR) positive breast cancer should additionally have received or be
ineligible for endocrine therapy.
Enhertu is a specifically
engineered HER2-directed antibody drug conjugate (ADC) being
jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.
The Food and Drug Administration's (FDA) BTD is designed to
accelerate the development and regulatory review of potential new
medicines that are intended to treat a serious condition and
address a significant unmet medical need. The new medicine needs to
have shown encouraging preliminary clinical results that
demonstrate substantial improvement on a clinically significant
endpoint over available medicines.
Up to half of all patients with breast cancer have tumours with a
HER2 immunohistochemistry (IHC) score of 1+, or 2+ in combination
with a negative in-situ hybridisation (ISH) test, a level of HER2
expression not currently eligible for HER2-targeted
therapy.1-4 Low
HER2 expression occurs in both HR-positive and HR-negative
disease.5
HER2 testing is routinely used to determine appropriate treatment
options for patients with metastatic breast cancer. Targeting the
lower range of expression in the HER2 spectrum may offer another
approach to delay disease progression and extend survival in
patients with metastatic breast cancer.6 Currently
chemotherapy remains the only treatment option for patients with
HR-positive tumours following progression on endocrine (hormone)
therapy.7 Few
targeted options are available for those who are
HR-negative.8
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca said: "Today's news is a significant validation of the
potential we see for the historic DESTINY-Breast04 trial to enable
a paradigm shift in how breast cancer is classified by targeting
the full spectrum of HER2 expression. Enhertu continues to show transformative potential,
and this milestone represents an important advance for patients
with HER2-low metastatic breast cancer who are in urgent need of
new treatment options and better outcomes."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo said:
"Historically, only patients with HER2-positive metastatic breast
cancer were shown to benefit from HER2-directed therapy.
DESTINY-Breast04, in which Enhertu showed a clinically meaningful survival
benefit in patients with HER2-low metastatic breast cancer, is
the first trial to demonstrate that selecting patients for
treatment based on low expression of HER2 has the potential to
change the diagnostic and treatment paradigms for these
patients. This Breakthrough Therapy Designation acknowledges
the potential of Enhertu to fulfil an unmet medical need and we look
forward to working closely with the FDA to bring the first
HER2-directed therapy to patients with metastatic breast cancer
whose tumours have lower levels of HER2
expression."
The FDA granted the BTD based on data from the pivotal
DESTINY-Breast04 Phase III trial which
reported positive high-level
results in
February 2022. In the trial, Enhertu 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 in all randomised
patients with HR-positive and HR-negative disease versus
physician's choice of chemotherapy, which is the current standard
of care. The safety profile of Enhertu was consistent with previous clinical trials
with no new safety concerns identified. The data will be presented
at an upcoming medical meeting.
This is the third BTD for Enhertu in breast cancer. Enhertu previously
received BTD's for the treatment of second-line HER2-positive
metastatic breast cancer in 2021 and later-line HER2-positive
metastatic breast cancer in 2017. Two additional BTD's
for Enhertu were granted in 2020 for HER2-mutant
metastatic non-small cell lung cancer (NSCLC) and HER2-positive
metastatic gastric cancer.
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 and in the
US.9,10 More
than two million cases of breast cancer were diagnosed in 2020
resulting in nearly 685,000 deaths globally.9 In
the US, more than 290,000 new cases are expected to be diagnosed in
2022, resulting in more than 43,000 deaths.11
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.12 HER2
expression is currently defined as either positive or negative, and
is determined by an IHC test which measures the amount of HER2
protein on a cancer cell, and/or an ISH test which counts the
copies of the HER2 gene in cancer cells.12,13 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-.12
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label,
registrational Phase III trial evaluating the efficacy and safety
of Enhertu (5.4mg/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 (HR-positive and HR-negative disease), OS in
patients with HR-positive disease and OS in all randomised patients
(HR-positive and HR-negative disease). 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 is also currently
under review in the US for the treatment of adult patients with
unresectable or metastatic non-small cell lung cancer (NSCLC) whose
tumours have a HER2 (ERBB2) mutation and who have received a prior
systemic therapy, and 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 (TSE: 4568) [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
that has been studied in HER2-negative early and 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, 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. 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.
2. Schalper K, et al. A retrospective population-based comparison
of HER2 immunohistochemistry and fluorescence in situ hybridization
in breast carcinomas. Arch Pathol Lab
Med. 2014;
138:213-219.
3. Schettini F, et al. Clinical, pathological, and PAM50 gene
expression features of HER2-low breast
cancer. npj Breast
Cancer. 2021; 7:1 ;
https://doi.org/10.1038/s41523-020-00208-2.
4. Denkert C, et al. Clinical and molecular characteristics of
HER2-low-positive breast cancer: pooled analysis of individual
patient data from four prospective, neoadjuvant clinical trials.
2021. Lancet
Oncol; 22:
1151-61.
5. 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.
6. Eiger D, et al. The Exciting New Field of HER2-Low Breast Cancer
Treatment. Cancers. 2021;
10.3390/cancers13051015.
7. Matutino A, et al. Hormone receptor-positive, HER2-negative
metastatic breast cancer: redrawing the
lines. Current
Oncology. 2018;
25(S1):S131-S141.
8. American Cancer Society. Breast Cancer Hormone Receptor Status.
Available at:
https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html.
Accessed April 2022.
9. 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.
10. CDC. United States Cancer Statistics: Data Visualizations.
Available at: https://gis.cdc.gov/Cancer/USCS/#/AtAGlance/. Last
accessed: April 2022.
11. American Cancer Society. Cancer Facts & Figures 2022.
Available at:
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html.
Last accessed: April 2022.
12. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
13. 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:
22 April 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|