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 March 2024
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
EMA validates Dato-DXd MAAs for NSQ NSCLC and BC
4 March 2024
Two datopotamab deruxtecan applications validated in the EU
for
patients with advanced nonsquamous non-small cell lung
cancer or HR-positive, HER2-negative breast cancer
Parallel applications based on TROPION-Lung01 and TROPION-Breast01
Phase III trial results demonstrating AstraZeneca and Daiichi
Sankyo's datopotamab deruxtecan significantly improved
progression-free survival vs. chemotherapy in two types of
cancer
The European Medicines Agency (EMA) has validated two marketing
authorisation applications (MAAs) for AstraZeneca and Daiichi
Sankyo's datopotamab deruxtecan (Dato-DXd) in two types of cancer.
One MAA is for the treatment of adult patients with locally
advanced or metastatic nonsquamous non-small cell lung cancer
(NSCLC) who require systemic therapy following prior treatment. The
other MAA is 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 progressed on and are
not suitable for endocrine therapy and received at least one
additional systemic therapy.
The validations confirm the completion of the applications and
commence the scientific review process by the EMA's Committee for
Medicinal Products for Human Use. The applications are based on
data from the pivotal TROPION-Lung01 and TROPION-Breast01 Phase
III trials presented during two Presidential Symposia at the 2023
European Society for Medical Oncology Congress.
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: "Our ambition is for datopotamab deruxtecan to
improve upon and replace conventional chemotherapy in the treatment
of multiple cancer types. Today's dual validation of our
applications in lung and breast cancers brings this potential
medicine a meaningful step closer to redefining treatment
expectations for patients with two of the most common cancers in
Europe."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The
EMA validation is an important first step toward bringing this
TROP2-directed antibody drug conjugate to eligible patients in
Europe with nonsquamous lung cancer and HR-positive, HER2-negative
breast cancer. This news builds on our recent regulatory progress
in the US, where our lung cancer application has been accepted and
our breast cancer application is underway, underscoring our
commitment to changing the standard of care by developing new
medicines to help as many patients worldwide as
possible."
Additional regulatory submissions for datopotamab deruxtecan in
lung cancer and breast cancer are underway in the US and
globally.
Notes
Advanced non-small cell lung cancer
Nearly 500,000 lung cancer cases were diagnosed in Europe in
2022.1 NSCLC
is the most common type of lung cancer, accounting for about 80% of
cases.1 Approximately
70% and 30% of NSCLC tumours are of nonsquamous or squamous
histology, respectively.2 While
immunotherapy and targeted therapies have improved outcomes in the
first-line setting, most patients eventually experience disease
progression and receive chemotherapy.3,4,5 For
decades, chemotherapy has been the last treatment available for
patients with advanced NSCLC, despite limited effectiveness and
known side effects.3,4,5
HR-positive breast cancer
More than 500,000 breast cancer cases were diagnosed in Europe in
2022.6 HR-positive,
HER2-negative breast cancer is the most common subtype, accounting
for more than 65% of diagnosed cases.7 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-).7,8 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.9,10
TROP2
TROP2 is a protein broadly expressed in several solid tumours,
including the majority of NSCLC and HR-positive, HER2-negative
breast cancer cases.11,12 High
TROP2 expression is associated with increased tumour progression
and poor survival.12,13 There
is currently no TROP2-directed ADC approved for the treatment of
lung cancer.14,15
TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label
Phase III trial evaluating the efficacy and safety of datopotamab
deruxtecan versus docetaxel in patients with locally advanced or
metastatic NSCLC with and without actionable genomic alterations
who require systemic therapy following prior treatment. Patients
with actionable genomic alterations were previously treated with
platinum-based chemotherapy and an approved targeted therapy.
Patients without known actionable genomic alterations were
previously treated, either in combination or sequentially, with
platinum-based chemotherapy and a PD-1 or PD-L1
inhibitor.
The dual primary endpoints of TROPION-Lung01 are progression-free
survival (PFS) as assessed by blinded independent central review
(BICR) and overall survival (OS). Key secondary endpoints include
investigator-assessed PFS, objective response rate (ORR), duration
of response (DoR), time to response, disease control rate (DCR) as
assessed by both BICR and investigator, and safety. TROPION-Lung01
enrolled approximately 600 patients in Asia, Europe, North America
and South America. For more information
visit ClinicalTrials.gov.
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 BICR and OS. Key secondary endpoints include ORR, DoR,
investigator-assessed PFS, DCR, 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 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 called TROPION is underway
globally with more than 14 trials evaluating the efficacy and
safety of datopotamab deruxtecan across multiple cancers, including
NSCLC, triple-negative breast cancer and HR-positive, HER2-negative
breast cancer. Beyond the TROPION programme, datopotamab deruxtecan
also is being evaluated in novel combinations in several ongoing
trials.
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 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. Cancer.net. Lung Cancer - Non-Small
Cell: Statistics. Available at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed March 2024.
2. National Cancer Institute. SEER
Cancer Statistics Factsheets: Lung and Bronchus Cancer, 2015.
Available at: https://seer.cancer.gov/archive/csr/1975_2012/results_merged/sect_15_lung_bronchus.pdf.
Accessed March 2024.
3. Chen R, et al. Emerging therapeutic
agents for advanced non-small cell lung
cancer. J Hemal
Oncol.
2020;13(1):58.
4. Majeed U, et al. Targeted therapy
in advanced non-small cell lung cancer: current advances and future
trends. J Hematol
Oncol.
2021;14(1):108.
5. Pircher A, et al. Docetaxel in the
treatment of non-small cell lung cancer (NSCLC) - an observational
study focusing on symptom improvement. Anticancer
Research. 2020;70(5):
287-294.
6. Globocan 2022. Europe. Available
at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf.
Accessed March 2024.
7. National Cancer Institute. SEER
cancer stat facts: female breast cancer subtypes. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed March 2024.
8. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
9. 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.
10. 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.
11. 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.
12. Mito R, et al. Clinical impact of TROP2
in non-small lung cancers and its correlation with abnormal p53
nuclear accumulation. Pathol Int. 2020;70(5): 287-294.
13. 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.
14. Rodríguez-Abreau D, et al.
Pemetrexed plus platinum with or without pembrolizumab in patients
with previously untreated metastatic nonsquamous NSCLC:
protocol-specified final analysis from
KEYNOTE-189. Ann Onc. 2021 Jul:32(7): 881-895.
15. American Cancer Society. Targeted Drug
Therapy for Non-Small Cell Lung Cancer. Available
at: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html.
Accessed March 2024.
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:
04 March 2024
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
|
AstraZeneca (PK) (USOTC:AZNCF)
Historical Stock Chart
From Dec 2024 to Jan 2025
AstraZeneca (PK) (USOTC:AZNCF)
Historical Stock Chart
From Jan 2024 to Jan 2025
