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 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu improved IDFS in early BC in DB-05
29 September 2025
Enhertu demonstrated
highly statistically significant and clinically meaningful
improvement in invasive disease-free survival vs. T-DM1 in
DESTINY-Breast05 Phase III trial in patients with high-risk early
breast cancer following neoadjuvant therapy
Second positive Phase III trial of AstraZeneca and Daiichi Sankyo's
Enhertu in HER2-positive early breast cancer reinforces its
potential to become a foundational treatment option in
curative-intent setting
Results from the DESTINY-Breast05 and DESTINY-Breast11
trials
will be presented at ESMO 2025 in a Presidential
Symposium
Positive high-level results from a planned interim analysis of the
DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a
highly statistically significant and clinically meaningful
improvement in invasive disease-free survival (IDFS) versus
trastuzumab emtansine (T-DM1) in patients with HER2-positive early
breast cancer with residual invasive disease in the breast or
axillary lymph nodes after neoadjuvant treatment and a high risk of
disease recurrence. This is the second positive Phase III trial
of Enhertu in the HER2-positive early breast cancer
setting following positive results from
the DESTINY-Breast11 Phase
III neoadjuvant trial earlier this year.
Overall survival (OS) was not mature at the time of this planned
interim analysis and will be assessed at a subsequent
analysis.
Currently, approximately half of patients with HER2-positive early
breast cancer have residual disease following neoadjuvant
treatment, putting them at an increased risk of disease
recurrence.1-7 Despite
receiving additional treatment in the post-neoadjuvant setting with
current standards of care, some patients still ultimately
experience tumour progression to metastatic
disease.8-10 New
treatment options are needed in the early breast cancer setting to
help reduce the likelihood of disease progression and improve
long-term outcomes for more patients.10-11
Susan Galbraith, Executive Vice President, Oncology
Haematology R&D, AstraZeneca, said: "This landmark trial is the
first to directly compare Enhertu and T-DM1 in early breast cancer, and the
results clearly show that Enhertu delivers superior outcomes, indicating that
it may be a better option for patients with high-risk HER2-positive
disease in the post-neoadjuvant setting. These results from
DESTINY-Breast05, coupled with DESTINY-Breast11, underscore our
commitment to moving Enhertu into early-stage HER2-positive breast cancer
where patients can achieve sustained long-term outcomes, increasing
the opportunity for cure."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "In
patients with early breast cancer with residual disease following
neoadjuvant treatment, it is critical to optimise treatment as this
represents the last opportunity to prevent progression to
metastatic disease. The results of DESTINY-Breast05 demonstrate
that treatment with Enhertu following surgery increases the length of
time patients are able to live free of invasive disease compared to
the existing standard of care, potentially offering patients with
HER2-positive early breast cancer a new treatment approach in this
curative-intent setting."
The safety profile of Enhertu observed in DESTINY-Breast05 was consistent
with its known profile with no new safety concerns
identified.
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.
Data from DESTINY-Breast05 (Abstract #LBA1) and DESTINY-Breast11
(Abstract #291O) will be presented during Presidential Symposium
1 on 18 October at the
upcoming European Society for Medical Oncology (ESMO) Congress
2025. The DESTINY-Breast05 data will also be shared with global
regulatory authorities.
DESTINY-Breast05 was conducted in collaboration with the National
Surgical Adjuvant Breast and Bowel Project Foundation (NSABP), the
German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische
Onkologie (AGO-B) and SOLTI Breast Cancer Research
Group.
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.12 More
than two million breast
cancer cases were diagnosed in 2022, with more than 665,000 deaths
globally.12
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours including breast
cancer.13 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.14 Approximately
one in five cases of breast cancer are considered
HER2-positive.15
Currently, approximately half of patients with HER2-positive early
breast cancer have residual disease following neoadjuvant
treatment, putting them at an increased risk of disease
recurrence.1-7 Despite
receiving additional treatment in the post-neoadjuvant setting,
some patients still ultimately experience tumour progression to
metastatic disease.8-10 Once
patients are diagnosed with metastatic disease, the five-year
survival rate drops from nearly 90 percent to approximately 30
percent.16 New
treatment options are needed in the early breast cancer setting to
help reduce the likelihood of disease progression in order to
improve long-term outcomes for more patients.10-11
DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label,
Phase III trial evaluating the efficacy and safety
of Enhertu (5.4 mg/kg) versus trastuzumab ematansine
(T-DM1) in patients with HER2-positive primary breast cancer that
are at high risk of recurrence and have residual invasive disease
in breast or axillary lymph nodes following neoadjuvant therapy.
High risk of recurrence was defined as presentation with inoperable
cancer (prior to neoadjuvant therapy) or pathologically positive
axillary lymph nodes following neoadjuvant
therapy.
The primary endpoint of DESTINY-Breast05 is investigator-assessed
IDFS. IDFS is defined as the time from randomisation until first
occurrence of invasive breast cancer recurrence, distant
recurrence, or death from any cause. The key secondary
endpoint is investigator-assessed disease-free survival. Other
secondary endpoints include OS, distant recurrence-free interval,
brain metastases-free interval and safety.
DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, Oceania,
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 85 countries/regions 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 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 85 countries/regions 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 45 countries/regions 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 60 countries/regions 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 may be
contingent upon verification and description of clinical benefit in
a confirmatory trial.
Enhertu (6.4mg/kg) is
approved in more than 70 countries/regions 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 may by contingent
upon verification and description of clinical benefit in a
confirmatory trial.
Enhertu (5.4mg/kg) is
approved in more than 10 countries/regions 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
efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Continued approval for this indication may be 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 monotherapy across multiple HER2-targetable
cancers. Trials in combination with other
anti-cancer treatments, such as immunotherapy, also are
underway.
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. 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
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Gianni L, et al. Efficacy and
safety of neoadjuvant pertuzumab and trastuzumab in women with
locally advanced, inflammatory, or early HER2-positive breast
cancer (NeoSphere): a randomised multicentre, open-label, phase 2
trial. Lancet
Oncol. 2012;13(1):25-32.
2. Schneeweiss A, et al. Pertuzumab
plus trastuzumab in combination with standard neoadjuvant
anthracycline-containing and anthracycline-free chemotherapy
regimens in patients with HER2-positive early breast cancer: a
randomized phase II cardiac safety study
(TRYPHAENA). Annals of
Oncol. 2013;
24:2278-2284.
3. Swain S, 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. Annals of
Oncology. 2018;
29:646-653.
4. Hurvitz S, et al. Neoadjuvant
Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth
Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From
the Phase III KRISTINE Study. J Clin
Oncol. 2019;
37:2206-2216.
5. Huober J, et al. Atezolizumab With
Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy
and Chemotherapy in Human Epidermal Growth Factor Receptor
2-Positive Early Breast Cancer: Primary Results of the Randomized
Phase III IMpassion050 Trial. J Clin
Oncol. 2022;
40:2946-2956.
6. Masuda N, et al. A randomized,
3-arm, neoadjuvant, phase 2 study comparing
docetaxel + carboplatin + trastuzumab + pertuzumab
(TCbHP), TCbHP followed by trastuzumab emtansine and pertuzumab
(T-DM1+P), and T-DM1+P in HER2-positive primary breast
cancer. Breast Cancer Res
Treat. 2020;
180:135-146.
7.
Gao H, et al. De-escalated neoadjuvant taxane plus trastuzumab and
pertuzumab with or without carboplatin in HER2-positive early
breast cancer (neoCARHP): A multicentre, open-label, randomised,
phase 3 trial. Presented ASCO Annual Meeting 2025.
8. Von Minckwitz G, et
al. Trastuzumab Emtansine for
Residual Invasive HER2-Positive Breast
Cancer. N Engl J
Med.
2019;380(7):617-628
9. Geyer C, et al. Survival with
Trastuzumab Emtansine in Residual HER2-Positive Breast
Cancer. N Engl J
Med. 2025;
392:249-57.
10.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer.
Version 4.2025.
11. Zaborowski AM, et al. Neoadjuvant
systemic therapy for breast cancer. Br J Surg. 2023;110(7):765-772.
12. 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.
13. Cheng X. A comprehensive review of HER2
in cancer biology and therapeutics. Genes. 2024;15(7):903.
14. 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.
15. Ahn S, et al. HER2 status in breast
cancer: changes in guidelines and complicating factors for
interpretation. J Pathol Transl
Med.
2019;54(1):34-44.
16.
National Cancer Institute. SEER Cancer Stat Facts: Female Breast
Cancer Subtypes. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed September 2025
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: 29 September 2025
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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