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 July 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 significantly improved PFS in lung cancer
This announcement contains inside information
3 July 2023
Datopotamab deruxtecan met dual primary endpoint of
progression-free survival in patients with advanced non-small cell
lung cancer in TROPION-Lung01 Phase III trial
First Phase III results for AstraZeneca and Daiichi Sankyo's
TROP2-directed antibody drug conjugate demonstrated statistically
significant
improvement in progression-free survival vs. standard chemotherapy
in previously treated locally advanced or metastatic
disease
Trial will continue to assess the dual primary endpoint of overall
survival
Positive high-level results from the TROPION-Lung01 Phase III
trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a
statistically significant improvement for the dual primary endpoint
of progression-free survival (PFS) compared to docetaxel, the
current standard of care chemotherapy, in patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC) treated
with at least one prior therapy.
For the dual primary endpoint of overall survival (OS), the data
were not mature and an early trend was observed in favour of
datopotamab deruxtecan versus docetaxel that did not meet the
prespecified threshold for statistical significance at this interim
analysis. The trial will continue as planned to assess OS with
greater maturity. The investigators and participants will remain
blinded to the results.
The safety profile of datopotamab deruxtecan was consistent with
previous clinical trials with no new safety signals identified. All
grade interstitial lung disease was generally consistent with prior
clinical trials, with the majority being low grade. Some Grade 5
events were observed.
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: "With TROPION-Lung01, we met the dual primary
endpoint of progression-free survival, challenging the entrenched
standard of care in a previously treated and unselected patient
population that has long deserved an alternative to chemotherapy.
These first Phase III trial results from the datopotamab
deruxtecan clinical programme provide compelling evidence for the
potential role this TROP2-directed antibody drug conjugate can play
in treating patients with lung cancer."
Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo,
said: "We are encouraged by the statistically significant results
of the dual primary endpoint of progression-free survival seen with
datopotamab deruxtecan and look forward to the final overall
survival analysis. We plan to share these data with regulatory
authorities to discuss next steps."
More than one million people worldwide are diagnosed with advanced
NSCLC each
year.1,2 While
immunotherapy and targeted therapies have improved outcomes in the
1st-line metastatic 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 in the absence of other treatment
options and despite limited effectiveness and known side
effects.3-5 TROP2
is a protein highly expressed in a large majority of lung
cancers. There are currently no TROP2-directed ADCs approved for
the treatment of patients with lung cancer.6-8
TROPION-Lung01 enrolled patients with and without actionable
genomic alterations, such as EGFR and ALK. Patients with actionable
genomic alterations were previously treated with platinum-based
chemotherapy and an approved targeted therapy. Patients without
actionable genomic alterations were previously treated,
concurrently or sequentially, with platinum-based chemotherapy and
a PD-1 or PD-L1 inhibitor.
The data will be presented at a forthcoming medical meeting and
shared with health authorities.
Notes
Non-small cell lung cancer
More than one million people worldwide are diagnosed with advanced
NSCLC each
year.1,2 While
immunotherapy and targeted therapies have improved outcomes in the
1st-line metastatic 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 in the absence of other treatment
options and despite limited effectiveness and known side
effects.3-5
TROP2 is a protein highly expressed in a large majority of lung
cancers.6 There
are currently no TROP2-directed ADCs approved for the treatment of
patients with 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 (6.0 mg/kg) versus docetaxel (75 mg/m2)
in patients with locally advanced or metastatic NSCLC, with or
without actionable genomic alterations, treated with at least one
prior therapy. Patients without actionable genomic alterations were
previously treated, concurrently or sequentially, with
platinum-based chemotherapy and a prior PD-1 or PD-L1 inhibitor.
Patients with actionable genomic alterations were previously
treated with platinum-based chemotherapy and targeted therapy as
approved for their detected genomic alteration.
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 and disease control
rate as assessed by both BICR and an investigator, and
safety.
TROPION-Lung01 enrolled approximately 600 patients at sites 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 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, 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 TROP2-targetable tumours,
including NSCLC, 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.
In NSCLC, the TROPION-Lung07, TROPION-Lung08 and AVANZAR Phase III
trials are evaluating datopotamab deruxtecan and immune checkpoint
inhibitor combinations as potential 1st-line treatment options for
patients with advanced or metastatic disease, a strategy informed
by the results of two early trials. AstraZeneca is also researching
a potential diagnostic test to help identify patients most likely
to benefit from treatment with datopotamab deruxtecan.
AstraZeneca and 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 Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Siegel R, et al. Cancer
Statistics, 2021. CA
Cancer J Clin. 2021;71:7-33.
2. World Health
Organization. International Agency for Research on Cancer. Lung
Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed July 2023.
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.
2013;33(9):3831-3836.
6. 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.
7. 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.
8. 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 July 2023.
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:
03 July 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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