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 May 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 improved OS in nonsquamous lung cancer
This announcement contains inside information
27 May 2024
Datopotamab deruxtecan showed clinically meaningful overall
survival
improvement vs. chemotherapy in patients with advanced
nonsquamous
non-small cell lung cancer in TROPION-Lung01 Phase III
trial
In the overall trial population, survival results numerically
favoured AstraZeneca and
Daiichi Sankyo's datopotamab deruxtecan but did not reach
statistical significance
TROPION-Lung01 previously met the dual primary
endpoint
of progression-free survival in the overall trial
population
Results support applications currently under review by
regulatory authorities globally including in the US and
EU
High-level overall survival (OS) results from
the TROPION-Lung01 Phase
III trial, which previously met the dual primary endpoint of
progression-free survival (PFS), numerically favoured datopotamab
deruxtecan (Dato-DXd) compared to docetaxel in the overall trial
population of patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) treated with at least one prior
line of therapy. Survival results did not reach statistical
significance in the overall trial population. In the prespecified
subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan
showed a clinically meaningful improvement in OS compared to
docetaxel, the current standard-of-care
chemotherapy.
The final analysis of OS builds on the positive progression-free
survival (PFS) results presented at
the 2023 European Society for Medical Oncology Congress which
showed datopotamab deruxtecan demonstrated a statistically
significant improvement in PFS in the overall trial population and
a clinically meaningful PFS benefit in patients with nonsquamous
NSCLC. In TROPION-Lung01, patient enrolment by tumour histology was
balanced across treatment arms and consistent with real-world
incidence with approximately 75% of patients having nonsquamous
NSCLC.1,2
The safety profile of datopotamab deruxtecan in TROPION-Lung01 was
consistent with the previous analysis including fewer dose
reductions or discontinuations due to adverse events compared to
docetaxel, and no new safety concerns identified. No new
interstitial lung disease events of any grade were adjudicated as
drug-related.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Datopotamab
deruxtecan is the only investigational therapy to show a clinically
meaningful survival improvement in patients with previously treated
nonsquamous non-small cell lung cancer versus docetaxel, which has
long been unsurpassed in this post-targeted treatment and
post-immunotherapy setting. These results reinforce the potential
for datopotamab deruxtecan to replace conventional chemotherapy in
this late-line setting and underscore our confidence in ongoing
trials evaluating this therapy in first-line lung
cancer."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo,
said: "The
improvement in overall survival seen with datopotamab deruxtecan
coupled with the previously reported clinically meaningful
progression-free survival, more than doubling of overall response
and prolonged duration of response compared to docetaxel suggest
that this TROP2-directed antibody drug conjugate could potentially
become an important new treatment for patients with nonsquamous
non-small cell lung cancer in this advanced setting. These data
will support our ongoing discussions with regulatory authorities
globally to potentially bring datopotamab deruxtecan to patients as
quickly as possible and mark another step forward in creating new
standards of care for patients with cancer."
Datopotamab deruxtecan is a specifically engineered TROP2-directed
DXd antibody drug conjugate discovered by Daiichi Sankyo and being
jointly developed by AstraZeneca and Daiichi Sankyo.
The data will be presented at a forthcoming medical meeting and
will support regulatory applications currently under review
globally, including in the US and EU for the treatment of adult
patients with locally advanced or metastatic nonsquamous NSCLC who
have received prior systemic therapy.
Notes
Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in
2022.3 NSCLC
is the most common type of lung cancer, accounting for about 80% of
cases.4 Approximately
75% and 25% of NSCLC tumours are of nonsquamous or squamous
histology, respectively.1 While
immunotherapy and targeted therapies have improved outcomes in the
1st-line setting, most patients eventually experience disease
progression and receive chemotherapy.5-7 For
decades, chemotherapy has been the last treatment available for
patients with advanced NSCLC, despite limited effectiveness and
known side effects.5-7
TROP2 is a protein broadly expressed in the majority of NSCLC
tumours.8 There
is currently no TROP2-directed ADC approved for the treatment of
lung cancer.9,10
TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label
Phase III trial evaluating the efficacy and safety of datopotamab
deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2)
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 platinum-based
chemotherapy and an approved targeted therapy. 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 PFS as assessed by
blinded independent central review (BICR) and OS. Key secondary
endpoints include investigator-assessed PFS, objective response
rate, duration of response, time to response, disease control rate
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.
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 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 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 (trastuzumab deruxtecan) 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 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. National Cancer
Institute. SEER Cancer Statistics Factsheets: Lung
and Bronchus Cancer, 1975-2017. Accessed
May 2024.
2. Ahn M-J, et al. Datopotamab deruxtecan (Dato-DXd) vs doxetaxel
in previously treated advanced/metastatic (adv/met) non-small cell
lung cancer (NSCLC): results of the randomized phase 3 study
TROPION-Lung01. Presented at: ESMO Congress 2023, 20-24 October
2023; Madrid, Spain. LBA12.
3. 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 May 2024.
4. Cancer.net. Lung
Cancer - Non-Small Cell: Statistics. Available
at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer.
Accessed May 2024.
5. Chen
R, et
al.
Emerging therapeutic agents for advanced non-small cell lung
cancer. J
Hematol Oncol.
2020;13(1):58.
6. 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.
7. Pircher,
A, et
al. Docetaxel in the Treatment
of Non-small Cell Lung Cancer (NSCLC) - An Observational Study
Focusing on Symptom Improvement. Anticancer
Research.
2013;33(9):3831-3836.
8. 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.
9. 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.
10. 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
May 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:
28 May 2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|
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