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 December 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu granted BTD for post-neoadjuvant early BC
22 December 2025
Enhertu granted
Breakthrough Therapy Designation in the US as post-neoadjuvant
therapy for patients with HER2-positive early breast
cancer
Tenth Breakthrough Therapy Designation for AstraZeneca and Daiichi
Sankyo's Enhertu with the latest based on DESTINY-Breast05 Phase
III trial results
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been granted
Breakthrough Therapy Designation (BTD) in the US for adult patients
with HER2-positive early breast cancer with residual invasive
disease in the breast and/or axillary lymph nodes after neoadjuvant
treatment and high risk of disease recurrence.
The Food and Drug Administration (FDA) BTD accelerates the
development and regulatory review of potential new medicines
intended to treat a serious condition and address a significant
unmet medical need.
The FDA granted this BTD based on results from
the DESTINY-Breast05 Phase
III trial presented in a Presidential Symposium at the 2025
European Society for Medical Oncology (ESMO) Congress and
subsequently published in The
New England Journal of Medicine.
Susan Galbraith, Executive Vice President, Oncology Haematology
R&D, AstraZeneca, said: "For patients with residual disease
after neoadjuvant treatment, the post-neoadjuvant setting
represents a critical opportunity to reduce the risk of recurrence
and prevent progression to metastatic
disease. This Breakthrough
Therapy Designation highlights the impressive clinical benefit
of Enhertu over the current standard of care and
underscores its potential to become an important treatment option
in the post-neoadjuvant setting."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This
tenth Breakthrough Therapy Designation reinforces
how Enhertu continues to deliver transformational
results that advance the treatment of breast cancer. We look
forward to working with the FDA with the goal of
bringing Enhertu to the post-neoadjuvant setting of
HER2-positive early breast cancer, as DESTINY-Breast05 clearly
demonstrated that Enhertu may help halt invasive disease recurrence
over the current standard of care, resulting in potentially more
patients achieving a cure."
DESTINY-Breast05 is the second positive trial
of Enhertu in early breast cancer in 2025. The first
trial, DESTINY-Breast11, evaluating patients with high-risk
HER2-positive disease in the neoadjuvant setting, is currently
under review by the FDA.
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.
Notes
Post-neoadjuvant Treatment for HER2-Positive Early Breast
Cancer
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.1 More
than two million breast cancer cases were diagnosed in 2022, with
more than 665,000 deaths globally.1
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours including breast
cancer.2 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.2 Approximately
one in five cases of breast cancer are considered HER2
positive.3
For patients with HER2-positive early breast cancer, achieving
pathologic complete response (pCR) with neoadjuvant treatment is
the earliest indicator of improved long-term
survival.4 However,
approximately half of patients who receive neoadjuvant treatment do
not experience pCR, putting them at increased risk of disease
recurrence.5-9
Despite receiving additional treatment with T-DM1 for residual
disease in the post-neoadjuvant setting, approximately 20% of
patients still experience invasive disease or death, with no
reduction in the risk of central nervous system
recurrence.10-11 Once
patients are diagnosed with metastatic disease, the five-year
survival rate drops from nearly 90% to approximately
30%.12
Post-neoadjuvant therapy represents a key opportunity to minimise
the risk of recurrence and prevent progression to metastatic
disease for patients with residual disease. 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.13,14
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
emtansine (T-DM1) in patients with HER2-positive early breast
cancer with residual invasive disease in breast or axillary lymph
nodes following neoadjuvant therapy and a high risk of
recurrence. 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
invasive disease-free survival (IDFS). IDFS is defined as the time
from randomisation until first invasive local, axillary or distant
recurrence or death from any cause. The key secondary endpoint is
investigator-assessed disease-free survival. Other secondary
endpoints include overall survival, distant
recurrence-free interval, brain metastases-free interval and
safety.
DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe,
North America, Oceania 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) in combination
with pertuzumab is approved in the US as a 1st-line treatment for
adult patients with unresectable or metastatic HER2-positive (IHC
3+ or ISH+) breast cancer, as determined by an FDA-approved test
based on the results from the DESTINY-Breast09 trial.
Enhertu (5.4mg/kg) is approved in
more than 90 countries/regions worldwide for the treatment of adult
patients with unresectable or metastatic HER2-positive (IHC 3+ or
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 55 countries/regions worldwide 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 IHC 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 be contingent
upon verification and description of clinical benefit in a
confirmatory trial.
Enhertu (5.4mg/kg)
is approved in more than 10 countries/regions worldwide 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 as a monotherapy, in combination or
sequentially with other cancer medicines 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 patients with 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. 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; 74(3):229-263.
2. Cheng X. A comprehensive review of
HER2 in cancer biology and therapeutics. Genes. 2024;15(7):903.
3. 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.
4. Spring LM, et al. Pathological
complete response after neoadjuvant chemotherapy and impact on
breast cancer recurrence and survival: a comprehensive
meta-analysis. Clin Cancer
Res. 2020;26(12):2838-2284.
5. 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.
6. 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.
7. 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.
8. 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.
9.
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.
10. Geyer C, et al. Survival with
Trastuzumab Emtansine in Residual HER2-Positive Breast
Cancer. N Engl J
Med. 2025; 392:249-57.
11.
NCCN Clinical Practice Guidelines in Oncology. Breast Cancer.
Version 4.2025.
12. National Cancer Institute. SEER
Cancer Stat Facts: Female Breast Cancer. Available
at: https://seer.cancer.gov/statfacts/html/breast.html. Accessed
December 2025.
13. Von Minckwitz G, et al. Trastuzumab
emtansine for residual invasive HER2-positive breast
cancer. N Engl J
Med. 2019;
380(7):617-628.
14. Zaborowski AM, et al. Neoadjuvant
systemic therapy for breast cancer. Br J Surg. 2023; 110(7):765-772.
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.
Date: 22 December 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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