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 December 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.
Dato-DXd NSQ NSCLC application withdrawn in EU
24 December 2024
Datopotamab deruxtecan application in the EU for patients with
advanced
nonsquamous non-small cell
lung cancer voluntarily withdrawn
AstraZeneca and Daiichi Sankyo have voluntarily withdrawn the
marketing authorisation application (MAA) in the EU for datopotamab
deruxtecan (Dato-DXd) for the treatment of adult patients with
locally advanced or metastatic nonsquamous non-small cell lung
cancer (NSCLC) based on the TROPION-Lung01 Phase
III trial.
The decision to withdraw the MAA was informed by feedback from the
Committee for Medicinal Products for Human Use of the European
Medicines Agency (EMA). AstraZeneca and Daiichi
Sankyo will continue to work to bring datopotamab deruxtecan
to patients with lung cancer in the EU who can benefit and are
committed to unlocking the potential of this medicine in lung
cancer through our robust clinical development programme which
includes seven pivotal trials in various lung cancer
settings.
AstraZeneca and Daiichi Sankyo's application in the EU for
datopotamab deruxtecan for the treatment of hormone receptor
(HR)-positive, HER2-negative metastatic breast cancer based on
the TROPION-Breast01 Phase
III trial remains under review.
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.
Notes
Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in
2022.1 In
Europe, nearly half a million lung cancer cases were diagnosed in
2022.1 Lung
cancer is broadly split into small or non-small cell lung cancer,
the latter accounting for about 80% of cases.2
While immunotherapy and targeted therapies have improved outcomes
in the 1st-line setting, most patients eventually experience
disease progression and receive chemotherapy.3-5 For
decades, chemotherapy has been the last treatment available for
patients with advanced NSCLC, despite limited effectiveness and
known side effects.3-5
TROP2 is a protein broadly expressed in the majority of NSCLC
tumours.6 There
is currently no TROP2-directed ADC approved for the treatment of
lung cancer.7,8
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 adult 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 an
approved targeted therapy and platinum-based chemotherapy. Patients
without known actionable genomic alterations were previously
treated, concurrently 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, duration of
response, time to response, and disease control rate as assessed by
both BICR and investigator, and safety.
TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe,
North America, Oceania and South America. For more information
visit ClinicalTrials.gov.
Primary results from TROPION-Lung01, as presented at
the European Society for Medical Oncology 2023 Congress, showed
datopotamab deruxtecan demonstrated a statistically significant
improvement in PFS over docetaxel. OS results
were presented at
the IASLC 2024 World
Conference on Lung Cancer hosted by the International Association
for the Study of Lung Cancer and simultaneously published in
the Journal of Clinical
Oncology in September
2024.
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.
Datopotamab deruxtecan has been granted Breakthrough
Therapy Designation by the US Food and Drug Administration for the
treatment of adult patients with locally advanced or metastatic
epidermal growth factor receptor-mutated (EGFRm) NSCLC with disease progression on or after
treatment with an EGFR-tyrosine kinase inhibitor and platinum-based
chemotherapy. AstraZeneca and Daiichi Sankyo have submitted a
Biologics License Application for datopotamab deruxtecan for this
potential indication.
Datopotamab deruxtecan clinical development programme
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. The programme includes seven Phase III trials in
lung cancer and five Phase III trials in breast cancer evaluating
datopotamab deruxtecan as a monotherapy and in combination with
other anticancer treatments in various settings.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu (trastuzumab deruxtecan)
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 lung cancer
AstraZeneca is working to bring patients with lung cancer closer to
cure through the detection and treatment of early-stage disease,
while also pushing the boundaries of science to improve outcomes in
the resistant and advanced settings. By defining new therapeutic
targets and investigating innovative approaches, the Company aims
to match medicines to the patients who can benefit
most.
The Company's comprehensive portfolio includes leading lung cancer
medicines and the next wave of innovations,
including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu and datopotamab deruxtecan in collaboration
with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with
HUTCHMED; as well as a pipeline of potential new medicines and
combinations across diverse mechanisms of
action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a
global coalition working to accelerate innovation and deliver
meaningful improvements for people with lung cancer, including and
beyond treatment.
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's innovative
medicines are sold in more than 125 countries and 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: Lung. Available
at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed December 2024.
2. American
Cancer Society. Key Statistics for Lung Cancer. Available
at: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer.
Accessed December 2024.
3. Chen
R, et al. Emerging therapeutic agents for advanced non-small cell
lung cancer. J Hematol 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. Mito
R, et al. Clinical impact of TROP2 in non-small cell lung cancers
and its correlationn with abnormal p53 nuclear
accumulation. Pathol Int.
2020;70(5):287-294.
7. 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 December 2024.
8. 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.
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.
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AstraZeneca
PLC
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Date:
24 December 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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