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 September 2023
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.
Dato-DXd improved PFS in breast cancer
This announcement contains inside information
22 September 2023
Datopotamab deruxtecan demonstrated statistically significant and
clinically meaningful progression-free survival benefit in patients
with HR-positive,
HER2-low or negative breast cancer in TROPION-Breast01 Phase III
trial
First Phase III results in breast cancer for
AstraZeneca
and Daiichi Sankyo's datopotamab deruxtecan
Plans for global regulatory submissions underway
Positive high-level results from the TROPION-Breast01 Phase III
trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a
statistically significant and clinically meaningful improvement for
the primary endpoint of progression-free survival (PFS) compared to
investigator's choice of chemotherapy in patients with inoperable
or metastatic hormone receptor (HR)-positive, HER2-low or negative
(IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated
with endocrine-based therapy and at least one systemic
therapy.
A trend in improvement for the dual primary endpoint of overall
survival (OS) was observed for datopotamab deruxtecan versus
chemotherapy. Data for OS were not mature at this interim analysis
and the trial will continue as planned to assess OS.
The safety profile of datopotamab deruxtecan was consistent with
previous clinical trials in breast cancer with no new safety
signals identified. All grade interstitial lung disease rates were
low.
Datopotamab deruxtecan is a specifically engineered TROP2-directed
DXd antibody drug conjugate (ADC) being jointly developed by
AstraZeneca and Daiichi Sankyo.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Today's TROPION-Breast01 news is a
significant development for patients with HR-positive, HER2-low or
negative metastatic breast cancer whose tumours have become
insensitive to endocrine therapy and who currently face poor
outcomes. We are encouraged by these positive
results."
Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo,
said: "The positive topline results from TROPION-Breast01
demonstrate the potential for datopotamab deruxtecan to become an
important treatment option for patients with HR-positive, HER2-low
or HER2-negative breast cancer in the second-line metastatic
setting. We look forward to realising the full potential of this
TROP2-directed antibody drug conjugate across breast cancer
subtypes through our ongoing Phase III programme, including two
trials in patients with triple-negative breast
cancer."
More than two million people worldwide are diagnosed with breast
cancer each year.1 HR-positive,
HER2-low or negative breast cancer is the most common subtype,
accounting for more than 65% of diagnosed cases.1,2 Standard
initial treatment for these patients is endocrine therapy but most
patients with advanced disease will develop resistance,
underscoring the need for additional options.3,4 TROP2
is a protein broadly expressed in HR-positive, HER2-low or negative
breast cancer.5,6
The data will be presented at a forthcoming medical meeting and
shared with health authorities.
AstraZeneca and Daiichi Sankyo have two additional Phase III trials
evaluating datopotamab deruxtecan in breast cancer.
TROPION-Breast02 is comparing datopotamab deruxtecan to
chemotherapy in patients with previously untreated locally
recurrent inoperable or metastatic triple negative breast cancer
(TNBC) who are not candidates for anti-PDL1 therapy.
TROPION-Breast03 is evaluating datopotamab deruxtecan with and
without Imfinzi (durvalumab) versus investigator's choice of
therapy in patients with Stage I-III TNBC with residual disease
after neoadjuvant therapy.
Notes
HR-positive breast cancer
Breast cancer is the most common cancer in the world and a leading
cause of cancer-related death.1 More
than two million breast cancer cases were diagnosed in 2020 with
nearly 685,000 deaths globally.1
Breast cancer is considered HR-positive, HER2-low or negative when
tumours test positive for oestrogen and/or progesterone hormone
receptors and negative or low for HER2 (measured as HER2 score of
IHC 0, IHC 1+ or IHC 2+/ISH-).2,7 HR-positive,
HER2-low or negative breast cancer is the most common subtype,
accounting for more than 65% of diagnosed cases.2 Approximately
30% of patients diagnosed with HR-positive, HER2-low or negative
metastatic breast cancer are expected to live five years after
their diagnosis.2
TROP2 is a protein broadly expressed in several solid tumours,
including HR positive, HER2-low or negative breast
cancer.5 TROP2
expression is associated with increased tumour progression and poor
survival in patients with breast cancer.5,6
TROPION-Breast01
TROPION-Breast01 is global, randomised, multicentre, open-label
Phase III trial evaluating the safety and efficacy of datopotamab
deruxtecan versus investigator's choice of single-agent
chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine)
in patients with inoperable or metastatic HR- positive, HER2-low or
negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have
previously progressed on or are not suitable for endocrine therapy
per investigator assessment.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed
by blinded independent central review (BICR) and OS. Key secondary
endpoints include objective response rate, duration of response,
investigator-assessed PFS, disease control rate and time to first
subsequent therapy.
TROPION-Breast01 enrolled more than 700 patients at sites in Asia,
Europe, North America, South America and Africa. For more
information visit ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational
TROP2-directed ADC. Designed using Daiichi Sankyo's proprietary DXd
ADC technology, datopotamab deruxtecan is one of five lead ADCs in
the oncology pipeline of Daiichi Sankyo, and one of the most
advanced programmes in AstraZeneca's ADC scientific platform.
Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1
monoclonal antibody, developed in collaboration with Sapporo
Medical University, attached to a number of topoisomerase I
inhibitor payloads (an exatecan derivative, DXd) via
tetrapeptide-based cleavable linkers.
A comprehensive development programme is underway globally with
more than 12 trials evaluating the efficacy and safety of
datopotamab deruxtecan across multiple tumours, including non-small
cell lung cancer, triple-negative breast cancer and hormone
receptor-positive, HER2-low or negative breast cancer. Beyond the
TROPION programme, datopotamab deruxtecan is also being evaluated
in novel combinations in several ongoing trials. AstraZeneca is
also researching a potential diagnostic test to help identify
patients most likely to benefit from treatment with datopotamab
deruxtecan.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu in March
2019 and datopotamab
deruxtecan in July
2020, except in Japan
where Daiichi Sankyo maintains exclusive rights for each ADC.
Daiichi Sankyo is responsible for the 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.
With Enhertu (trastuzumab deruxtecan), a HER2-directed
ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes
in previously treated HER2-positive and HER2-low metastatic breast
cancer and are exploring its potential in earlier lines of
treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve
outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the
HR-positive space with next-generation SERD and potential new
medicine camizestrant as well as a potential first-in-class AKT
kinase inhibitor, capivasertib. AstraZeneca is also collaborating
with Daiichi Sankyo to explore the potential of TROP2-directed ADC,
datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option
that has been studied in early and metastatic breast cancer
patients with an inherited BRCA mutation. AstraZeneca with MSD
(Merck & Co., Inc. in the US and Canada) continues to
research Lynparza in these settings and to explore its
potential in earlier disease.
To bring much-needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is evaluating the potential of datopotamab deruxtecan
alone and in combination with
immunotherapy Imfinzi,
capivasertib in combination with chemotherapy,
and Imfinzi in combination with other oncology
medicines, including Lynparza and Enhertu.
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 social media @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. National
Cancer Institute. Surveillance, Epidemiology and End Results
Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed September 2023.
3.
Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors
Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone
receptor-positive, HER2-negative metastatic breast cancer. J
Cancer. 2020; 10.7150/jca.48944.
4. Lloyd M R, et
al. Mechanisms of Resistance to
CDK4/6 Blockade in Advanced Hormone Receptor-positive,
HER2-negative Breast Cancer and Emerging Therapeutic
Opportunities. Clin Cancer Res. 2022;
28(5):821-30.
5. Goldenberg D, et al. The emergence
of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer
target. Oncotarget. 2018;9(48): 28989-29006.
6.
Vidula N, et al. Trophoblast Cell Surface Antigen 2 gene (TACSTD2)
expression in primary breast cancer. Breast Cancer Res Treat. 2022
Aug;194(3):569-575.
7. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
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 September 2023
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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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