a9023i
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 2024
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.
FDA accepts Dato-DXd BLA for breast cancer
2 April
2024
Datopotamab deruxtecan Biologics License Application accepted in
the US for patients with previously treated metastatic HR-positive,
HER2-negative breast cancer
Application based on results from the TROPION-Breast01 Phase III
trial
Additional BLA under review in the US for AstraZeneca and Daiichi
Sankyo's datopotamab deruxtecan for patients with advanced
nonsquamous non-small cell lung cancer
AstraZeneca and Daiichi Sankyo's Biologics License Application
(BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in
the US for the treatment of adult patients with unresectable or
metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0,
IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior
systemic therapy for unresectable or metastatic disease. The
Prescription Drug User Fee Act date, the US Food and Drug
Administration (FDA) action date for its regulatory decision, is
during the first quarter of 2025.
The BLA is based on results from the pivotal
TROPION-Breast01 Phase III trial in which datopotamab deruxtecan
demonstrated a statistically significant and clinically meaningful
improvement for the dual primary endpoint of progression-free
survival (PFS) compared to investigator's choice of chemotherapy in
patients with unresectable or metastatic HR-positive, HER2-negative
breast cancer previously treated with endocrine-based therapy and
at least one systemic therapy. For the dual primary endpoint of
overall survival (OS), interim results numerically favoured
datopotamab deruxtecan over chemotherapy but were not mature at the
time of data cut-off. The trial is ongoing and OS will be assessed
at future analyses.
Datopotamab deruxtecan is a specifically engineered TROP2-directed
DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and
being jointly developed by AstraZeneca and Daiichi
Sankyo.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Despite marked progress in the treatment of
HR-positive, HER2-negative breast cancer, most patients with
advanced disease develop endocrine resistance and face the prospect
of one or several lines of chemotherapy. If approved, datopotamab
deruxtecan has the potential to provide these patients an
efficacious and better tolerated alternative to conventional
chemotherapy."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The
FDA's acceptance of the BLA brings us closer to providing patients
with previously treated HR-positive, HER2-negative breast cancer an
alternative option to conventional chemotherapy earlier in the
metastatic setting. Following our recently accepted application for
advanced nonsquamous non-small cell lung cancer in the US, along
with additional regulatory reviews underway in China, the EU, Japan
and other regions, we are working swiftly to bring datopotamab
deruxtecan as a potential new treatment option to patients around
the world."
Results from TROPION-Breast01 were
presented during a Presidential Symposium at the 2023 European
Society for Medical Oncology Congress and in an oral presentation
at the 2023 San Antonio Breast Cancer
Symposium.
The safety profile of datopotamab deruxtecan was consistent with
that observed in other ongoing trials with no new safety concerns
identified.
An additional BLA for datopotamab deruxtecan based on results from
the pivotal TROPION-Lung01 Phase III trial is under review in the
US for the treatment of adult patients with locally advanced
or metastatic nonsquamous non-small cell lung cancer (NSCLC) who
have received prior systemic therapy. Additional regulatory
submissions for datopotamab deruxtecan in lung and breast cancer
are underway globally.
Notes
HR-positive breast cancer
More than 275,000 breast cancer cases were diagnosed in the US in
2022.1 HR-positive,
HER2-negative breast cancer is the most common subtype, accounting
for more than 65% of diagnosed cases.2 Breast
cancer is considered HR-positive, HER2-negative when tumours test
positive for oestrogen and/or progesterone hormone receptors and
negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC
2+/ISH-).2,3 Standard
initial treatment for this subtype of breast cancer is endocrine
therapy but most patients with advanced disease will develop
resistance, underscoring the need for additional
options.4,5
TROP2 is a protein broadly expressed in HR-positive, HER2-negative
breast cancer and is associated with increased tumour progression
and poor survival.6,7
TROPION-Breast01
TROPION-Breast01 is a global, randomised, multicentre, open-label
Phase III trial evaluating the efficacy and safety of datopotamab
deruxtecan versus investigator's choice of single-agent
chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine)
in patients with unresectable or metastatic HR-positive,
HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have
progressed on and are not suitable for endocrine therapy per
investigator assessment and have received at least one additional
systemic therapy for unresectable or metastatic
disease.
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, time to first
subsequent therapy and safety. TROPION-Breast01 enrolled more than
700 patients in Africa, Asia, Europe, North America and South
America. 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 six DXd 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 humanised 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 global clinical development programme is underway
with more than 20 trials evaluating the efficacy and safety of
datopotamab deruxtecan across multiple cancers, including NSCLC,
triple-negative breast cancer (TNBC) and HR-positive, HER2-negative
breast cancer.
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 and Zoladex (goserelin)
and aims to reshape the HR-positive space with first-in-class AKT
inhibitor, Truqap, and next-generation SERD and potential new
medicine camizestrant. 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) continue to
research Lynparza in these settings and to explore its
potential in earlier disease.
To bring much-needed treatment options to patients
with TNBC, an aggressive form of breast cancer,
AstraZeneca is evaluating the potential of datopotamab deruxtecan
alone and in combination with
immunotherapy Imfinzi (durvalumab), Truqap 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, Respiratory &
Immunology and Vaccines & Immune Therapies. 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. World Health Organization. Global
Cancer Observatory: United States of America. Available
at: https://gco.iarc.who.int/media/globocan/factsheets/populations/840-united-states-of-america-fact-sheet.pdf.
Accessed April 2024.
2. National Cancer
Institute. SEER cancer stat facts: female breast cancer subtypes.
Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed April 2024.
3. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
4. 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.
5. Lloyd MR, 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.
6. 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.
7. Vidula N, et al. Sacituzumab
govitecan: Antibody-drug conjugate in triple negative breast cancer
and other solid tumours. Breast Cancer Res
Treat. 2022 Aug;194(3):
569-575.
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: 2
April 2024
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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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