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 September 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.
Final OS results reported for TROPION-Breast01
23 September 2024
Datopotamab deruxtecan final overall survival results reported
in
patients with metastatic HR-positive, HER2-low or negative breast
cancer in
TROPION-Breast01 Phase III trial
Survival results for AstraZeneca and Daiichi Sankyo's datopotamab
deruxtecan in TROPION-Breast01 did not achieve statistical
significance versus chemotherapy
Trial previously met the dual primary
endpoint of progression-free survival
High-level results from the TROPION-Breast01 Phase III trial of
datopotamab deruxtecan (Dato-DXd) compared to investigator's choice
of chemotherapy, which previously met the dual primary endpoint of
progression-free survival (PFS), did not achieve statistical
significance in the final overall survival (OS) analysis in
patients with inoperable or metastatic hormone receptor
(HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-)
breast cancer previously treated with endocrine-based therapy and
at least one systemic therapy.
This analysis follows the positive PFS results presented at
the 2023 European Society for Medical Oncology Congress which
showed datopotamab deruxtecan demonstrated a statistically
significant and clinically meaningful improvement in PFS. An
improvement in patient-reported outcomes was also
seen.1 The
PFS data and additional results for key secondary endpoints
were published this
month in the Journal of
Clinical Oncology.
The safety profile of datopotamab deruxtecan was consistent with
that observed in the previous analysis including lower rates of
Grade 3 or higher treatment-related adverse events compared to
chemotherapy, and no new safety concerns identified. All grade
interstitial lung disease (ILD) rates remained
low with
no new Grade 3 or higher ILD events observed.
With multiple antibody drug conjugates (ADCs) approved during the
course of the trial, including Enhertu (trastuzumab deruxtecan), subsequent
treatment following patients' disease progression or treatment
discontinuation is likely to have affected survival
results.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The metastatic HR-positive breast cancer
treatment landscape has advanced remarkably in the last several
years to the benefit of patients. Based on the TROPION-Breast01
results, there is evidence of the clinical value of datopotamab
deruxtecan in this setting. We will continue discussions with
regulatory authorities and apply insights from these results to our
clinical development programme for datopotamab deruxtecan in breast
cancer."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said:
"Datopotamab deruxtecan has previously shown a statistically
significant progression-free survival benefit in TROPION-Breast01,
a result supported by multiple meaningful secondary measures
including patient-reported outcomes. We are proud to have brought
forth a new standard of care for patients with metastatic breast
cancer with Enhertu and we remain committed to making
datopotamab deruxtecan another potential option for patients who
can benefit."
Datopotamab deruxtecan is a specifically engineered TROP2-directed
DXd ADC discovered by Daiichi Sankyo and being jointly developed by
AstraZeneca and Daiichi Sankyo.
The data will be presented at a forthcoming medical meeting and
shared with regulatory authorities currently reviewing applications
for this indication.
In addition to TROPION-Breast01, AstraZeneca and Daiichi Sankyo are
evaluating datopotamab deruxtecan alone and with immunotherapy as
treatment for patients with triple-negative or HR-low,
HER2-negative breast cancers in the TROPION-Breast02, TROPION-Breast03, TROPION-Breast04 and TROPION-Breast05 Phase
III trials.
Notes
HR-positive breast cancer
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.2 More
than two million breast cancer cases were diagnosed in 2022 with
more than 665,000 deaths globally.2 While
survival rates are high for those diagnosed with early breast
cancer, less than 35% of patients diagnosed with or who progress to
metastatic disease are expected to live five years following
diagnosis.3
Approximately 70% of diagnosed cases are considered what has been
historically called HR-positive, HER2-negative breast cancer
(measured as HER2 score of IHC 0, IHC 1+ or IHC
2+/ISH-).3 Endocrine
therapies are widely given consecutively in the early lines of
treatment for HR-positive metastatic breast cancer; however, after
two lines of treatment, further efficacy from endocrine therapy is
often limited.4 The
current standard of care following endocrine therapy is
chemotherapy, which is associated with poor response rates and
outcomes.4-7
TROP2 is a protein broadly expressed in HR-positive, HER2-negative
breast cancer and is associated with increased tumour progression
and poor survival.8,9
TROPION-Breast01
TROPION-Breast01 is a global, randomised, multicentre,
open-label Phase III trial evaluating the efficacy and safety of
datopotamab deruxtecan (6.0mg/kg) versus investigator's choice of
single-agent chemotherapy (eribulin, capecitabine, vinorelbine or
gemcitabine) in adult patients with unresectable or metastatic
HR-positive, HER2-low or 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.
Following disease progression or discontinuation of datopotamab
deruxtecan or chemotherapy, patients had the option to receive
subsequent treatment at the discretion of their physician.
Crossover between trial arms was not permitted.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed
by blinded independent central review 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. 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 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, 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.
Pernas S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy
in previously-treated inoperable or metastatic hormone
receptor-positive, HER2-negative (HR+/HER2-) breast cancer:
Patient-reported outcomes (PROs) from the TROPION-Breast01 study.
Presented at: ASCO Congress 2024; 31 May - 4 June, 2024; Chicago,
IL. Abstract 1006.
2.
Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries.
CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834.
3. National Cancer Institute.
Surveillance, Epidemiology and End Results Program. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed August 2024
4. Manohar P, et al. Updates in
endocrine therapy for metastatic breast
cancer. Cancer Biol
Med. 2022 Feb 15;
19(2):202-212.
5. Cortes J, et al. Eribulin
monotherapy versus treatment of physician's choice in patients with
metastatic breast cancer (EMBRACE): a phase 3 open-label randomised
study. Lancet. 2011;377:914-923.
6. Yuan P, et al. Eribulin mesilate
versus vinorelbine in women with locally recurrent or metastatic
breast cancer: A randomised clinical
trial. Eur
J Cancer.
2019;112:57-65.
7. Jerusalem G, et al. Everolimus Plus
Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen
Receptor-Positive, HER2-Negative Advanced Breast
Cancer. JAMA Oncol. 2018;4(10):1367-1374.
8.
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.
9. Vidula N, et al.
Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in
primary breast cancer. 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.
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AstraZeneca
PLC
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Date:
23 September 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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