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 2025
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu improved pCR in early-stage breast cancer
07 May 2025
Enhertu followed
by THP before surgery showed statistically significant and
clinically meaningful improvement in pathologic complete response
in patients with high-risk HER2-positive early-stage breast cancer
in DESTINY-Breast11 Phase III trial
AstraZeneca and Daiichi Sankyo's Enhertu followed by
THP
showed an improved safety profile vs. standard of care
First Phase III trial to demonstrate benefit of Enhertu in early
breast cancer
Positive high-level results from the DESTINY-Breast11 Phase III
trial showed Enhertu (trastuzumab deruxtecan) followed by
paclitaxel, trastuzumab and pertuzumab (THP) demonstrated a
statistically significant and clinically meaningful improvement in
pathologic complete response (pCR) rate versus standard of care
(dose-dense doxorubicin and cyclophosphamide followed by THP
[ddAC-THP]) when used in the neoadjuvant setting (before surgery)
in patients with high-risk, locally advanced HER2-positive
early-stage breast cancer. Pathologic complete response is defined
as no evidence of invasive cancer cells in the removed breast
tissue and lymph nodes following treatment.
The secondary endpoint of event-free survival (EFS) was not mature
at the time of analysis; however, EFS data showed an early positive
trend favouring Enhertu followed by THP compared to standard of
care. The trial will continue to follow EFS.
Approximately one in three patients with early-stage breast cancer
are considered high risk, as they are more likely to experience
disease recurrence and have a poor prognosis.1,2 Achieving
pCR in early-stage HER2-positive breast cancer is associated with
improved long-term outcomes.2,3 The
current standard of care in many regions of the world in this
neoadjuvant setting involves combination chemotherapy
regimens.2 These
regimens often include anthracyclines, which can be challenging for
patients to tolerate and may result in long-term cardiovascular
side effects.4 Further,
nearly half of patients who receive neoadjuvant treatment do not
achieve pCR, reinforcing the need for new treatment
options.2,3
Susan Galbraith, Executive Vice President, Oncology Haematology
R&D, AstraZeneca, said: "The clinically meaningful improvement
in pathologic complete response and the safety data seen in
DESTINY-Breast11 highlight the potential
of Enhertu to
challenge the current standard of care in early-stage HER2-positive
breast cancer. Enhertu is already an important treatment option in
the metastatic setting, and these data have the potential to allow
this medicine to move into early stages of disease where cure is
possible."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "There
are still many patients with early-stage breast cancer who do not
achieve a pathologic complete response with treatment in the
neoadjuvant setting, increasing the risk of disease recurrence.
These topline results from DESTINY-Breast11 demonstrate
that Enhertu followed by THP could offer patients with
HER2-positive breast cancer a promising new treatment approach
prior to surgery, setting more patients on a path towards a
potential cure."
Enhertu followed by THP
showed an improved safety profile compared to ddAC-THP. The safety
profiles of Enhertu and THP were consistent with the known
profiles of each individual medicine with no new safety concerns
identified. Rates of interstitial lung disease were similar across
the Enhertu followed by THP and the ddAC-THP arms as
determined by an independent adjudication
committee.
Following a recommendation by the Independent Data Monitoring
Committee, patient enrolment in a third arm of the trial
evaluating Enhertu alone was closed after a previous interim
efficacy assessment of the trial arms.
Data from DESTINY-Breast11 will be presented at an upcoming medical
meeting and shared with regulatory authorities.
Enhertu is a specifically
engineered HER2-directed DXd antibody drug conjugate (ADC)
discovered by Daiichi Sankyo and being jointly developed and
commercialised by AstraZeneca and Daiichi
Sankyo.
Enhertu has demonstrated
improved outcomes in six Phase III breast cancer trials across
different subtypes and stages of disease, including the recently
announced DESTINY-Breast09 Phase
III trial in the 1st-line HER2-positive metastatic
setting. Enhertu is also being studied in several ongoing
breast cancer trials including the DESTINY-Breast05 Phase III trial
which is evaluating Enhertu in the high-risk adjuvant early
HER2-positive setting.
Notes
HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.5 More
than two million breast
cancer cases were diagnosed in 2022, with more than 665,000 deaths
globally.5
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours including breast
cancer.6 HER2
protein overexpression may occur as a result of HER2 gene
amplification and is often associated with aggressive disease and
poor prognosis in breast cancer.7 Approximately
one in five cases of breast cancer are considered
HER2-positive.8
DESTINY-Breast11
DESTINY-Breast11 is a global, multicentre, randomised,
open-label, Phase III trial evaluating the efficacy and safety of
neoadjuvant Enhertu (5.4mg/kg) monotherapy
or Enhertu followed by THP vs. the standard of care
regimen in patients with high-risk (lymph node positive [N1-3] or
primary tumour stage T3-4), locally advanced or inflammatory
HER2-positive early-stage breast cancer.
Patients were randomised 1:1:1 to receive either eight cycles
of Enhertu monotherapy; four cycles
of Enhertu followed by four cycles of THP; or four
cycles of ddAC (dose-dense doxorubicin and cyclophosphamide)
followed by four cycles of THP.
The primary endpoint of DESTINY-Breast11 is pCR (absence of
invasive disease in the breast and lymph nodes). Secondary
endpoints include EFS, invasive disease-free survival, overall
survival and safety.
DESTINY-Breast11 enrolled 927 patients across multiple
sites in Asia, Europe, North America and South
America. For more information about the trial,
visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed
ADC. Designed using Daiichi Sankyo's proprietary DXd ADC
Technology, Enhertu is the lead ADC in the oncology portfolio of
Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC
scientific platform. Enhertu consists of a HER2 monoclonal antibody
attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable
linkers.
Enhertu (5.4mg/kg) is
approved in more than 75 countries worldwide for the treatment of
adult patients with unresectable or metastatic HER2-positive
(immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+)
breast cancer who have received a (or one or more) prior
anti-HER2-based regimen, either in the metastatic setting or in the
neoadjuvant or adjuvant setting, and have developed disease
recurrence during or within six months of completing therapy based
on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is
approved in more than 75 countries worldwide for the treatment of
adult patients with unresectable or metastatic HER2-low (IHC 1+ or
IHC 2+/ ISH-) breast cancer who have received a prior systemic
therapy in the metastatic setting or developed disease recurrence
during or within six months of completing adjuvant chemotherapy
based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is
approved in more than 30 countries for the treatment of adult
patients with unresectable or metastatic hormone receptor
(HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow
(IHC 0 with membrane staining) breast cancer, as determined by a
locally or regionally approved test, that have progressed on one or
more endocrine therapies in the metastatic setting based on the
results from the DESTINY-Breast06 trial.
Enhertu (5.4mg/kg) is
approved in more than 50 countries worldwide for the treatment of
adult patients with unresectable or metastatic non-small cell lung
cancer (NSCLC) whose tumours have
activating HER2 (ERBB2) mutations, as detected by a locally or
regionally approved test, and who have received a prior systemic
therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials.
Continued approval in China and the US for this indication is
contingent upon verification and description of clinical benefit in
a confirmatory trial.
Enhertu (6.4mg/kg) is
approved in more than 65 countries worldwide for the treatment of
adult patients with locally advanced or metastatic HER2-positive
(IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based regimen
based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials.
Continued approval in China for this indication will depend on
whether a randomised controlled confirmatory clinical trial can
demonstrate clinical benefit in this
population.
Enhertu (5.4mg/kg) is
approved in the US and other countries for the treatment of adult
patients with unresectable or metastatic HER2-positive (IHC 3+)
solid tumours who have received prior systemic treatment and have
no satisfactory alternative treatment options based on the results
from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Continued approval for this indication in the US is contingent upon
verification and description of clinical benefit in a confirmatory
trial.
Enhertu development programme
A comprehensive global clinical development programme is underway
evaluating the efficacy and safety of Enhertu as monotherapy or in combination or
sequentially with other anti-cancer therapies across multiple
HER2-targetable cancers.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu in March
2019 and Datroway (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 Datroway.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is challenging, and redefining, 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, AstraZeneca and Daiichi Sankyo are aiming to
improve outcomes in previously treated HER2-positive, HER2-low and
HER2-ultralow 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 (fulvestrant) and Zoladex (goserelin)
and aims to reshape the HR-positive space with first-in-class AKT
inhibitor, Truqap (capivasertib),
the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and
next-generation oral SERD and potential new medicine
camizestrant.
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. AstraZeneca is also exploring the
potential of saruparib, a potent and
selective inhibitor of PARP1, in combination with
camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced
breast cancer.
To bring much-needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is collaborating with Daiichi Sankyo to
evaluate the potential of Datroway alone and in combination with
immunotherapy Imfinzi (durvalumab).
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
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References
1.
National Cancer Institute. SEER Cancer Stat Facts: Female Breast
Cancer Subtypes. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed May 2025.
2. Spring LM, et al. Pathologic
Complete Response after Neoadjuvant Chemotherapy and Impact on
Breast Cancer Recurrence and Survival: A Comprehensive
Meta-analysis. Clin Cancer
Res. 2020; 26(12):
2838-2848.
3. Antonini M, et al. Pathologic
Complete Response and Breast Cancer Survival Post-Neoadjuvant
Chemotherapy: A Systematic Review and Meta-Analysis of Real-World
Data. Heliyon. 2025;ePub ahead of print:
e43069
4. Swain SM, et al. Pertuzumab,
trastuzumab, and standard anthracycline- and taxane-based
chemotherapy for the neoadjuvant treatment of patients with
HER2-positive localized breast cancer (BERENICE): a phase II,
open-label, multicenter, multinational cardiac safety
study. Ann Oncol. 2018;29(3):646-653
5. 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;10.3322/caac.21834.
6. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
7. Tarantino P, et al. ESMO expert
consensus statements (ECS) on the definition, diagnosis, and
management of HER2-low breast cancer. J An
Onc.
2023;34(8):645-659.
8. Ahn S, et al. HER2 status in breast
cancer: changes in guidelines and complicating factors for
interpretation. J Pathol Transl
Med.
2019;54(1):34
Matthew Bowden
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:
07 May 2025
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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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