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 2026
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in EU for 1L HER2-positive mBC
01 September 2026
Enhertu plus
pertuzumab approved in the EU as first new regimen in more than a
decade for the 1st-line treatment of patients with HER2-positive
metastatic breast cancer
Based on DESTINY-Breast09 Phase III trial which showed AstraZeneca
and Daiichi Sankyo's Enhertu plus pertuzumab reduced the risk of
disease progression or death by 44% vs. THP with median
progression-free survival exceeding three years
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) in combination
with pertuzumab has been approved in the European Union (EU) for
the 1st-line treatment of adult patients with unresectable or
metastatic HER2-positive breast cancer.
The approval by the European Commission follows
the positive
opinion of the Committee
for Medicinal Products for Human Use of the European Medicines
Agency and is based on results from the DESTINY-Breast09 Phase
III trial presented at the 2025 American Society of Clinical
Oncology Annual Meeting and subsequently published
in The
New England Journal of Medicine.1
Cristina Saura, MD, PhD, Vall d'Hebron University Hospital and Vall
d'Hebron Institute of Oncology (VHIO), Barcelona, steering
committee member and investigator for the DESTINY-Breast09 trial,
said: "For patients diagnosed with HER2-positive metastatic breast
cancer, maintaining disease control for as long as possible in the
first-line setting is a critical treatment goal. The combination of
trastuzumab deruxtecan and pertuzumab represents a significant
therapeutic advance, with progression-free survival exceeding three
years compared to approximately two years with the current standard
of care, and has the potential to become the new first-line
standard of care."
Dave Fredrickson, Executive Vice President, Oncology Haematology
Business Unit, AstraZeneca, said: "This approval
brings Enhertu to patients in the EU earlier in the course
of their metastatic disease and sets a new benchmark for
progression-free survival in the first-line setting. HER2-positive
metastatic breast cancer is an aggressive disease, so to give
patients the best chance of improving long-term outcomes, it is
critical to initiate effective HER2-directed therapy early and
continue treatment for as long as patients
benefit."
Ken Keller, Global Head of Oncology Business, and President and
CEO, Daiichi Sankyo, Inc., said: "This milestone marks the second
new indication for Enhertu in the EU in just two months following the
recent tumour agnostic approval, underscoring our goal to
bring this medicine to more eligible patients as quickly as
possible. This approval of Enhertu in combination with pertuzumab has the
potential to reshape clinical practice in the first-line treatment
setting for patients with HER2-positive metastatic breast
cancer."
In DESTINY-Breast09, Enhertu in combination with pertuzumab reduced the
risk of disease progression or death by 44% versus a taxane,
trastuzumab and pertuzumab (THP) (based on a hazard ratio of 0.56;
95% confidence interval [CI] 0.44-0.71; p<0.00001) in patients
with HER2-positive metastatic breast cancer who had not received
prior chemotherapy or HER2-targeted therapy or had received
neoadjuvant or adjuvant HER2-targeted therapy more than six months
before the diagnosis of advanced or metastatic disease. Median
progression-free survival (PFS) was 40.7 months
with Enhertu in combination with pertuzumab compared to
26.9 months with THP as assessed by blinded independent central
review (BICR).
The safety profile of Enhertu plus pertuzumab was consistent with the
known profiles of each individual treatment with no new safety
concerns identified.
Based on the results of DESTINY-Breast09, Enhertu in combination with pertuzumab has been
included in the ESMO Clinical Practice Guidelines as a Category IA
1st-line treatment option for patients with metastatic
HER2-positive breast cancer, regardless of hormone receptor (HR)
status.2
Enhertu is also under
review in the EU for patients with HER2-positive breast cancer who
have residual invasive disease after neoadjuvant HER2-targeted
treatment based on data from the DESTINY-Breast05 trial.
Enhertu is a specifically
engineered HER2-directed DXd antibody drug conjugate (ADC)
discovered by Daiichi Sankyo (TSE: 4568) and being jointly
developed and commercialised by AstraZeneca and Daiichi
Sankyo.
Financial considerations
Following this approval in the EU, an amount of $100 million is due
from AstraZeneca to Daiichi Sankyo as a milestone payment for the
1st-line unresectable or metastatic HER2-positive breast cancer
indication. Sales of Enhertu in most EU territories are recognised by
Daiichi Sankyo. For further details on the financial arrangements,
please consult the collaboration agreement
from March
2019.
Notes
HER2-positive metastatic breast cancer
Breast cancer is the most common cancer in women worldwide and the
leading cause of cancer-related death among
women.3 Approximately,
2.4 million breast cancer cases were diagnosed in 2024, with more
than 690,000 deaths globally.3 In
Europe, approximately 540,000 cases of breast cancer were diagnosed
in 2024, with more than 140,000 deaths.4 While
survival rates are high for those diagnosed with early breast
cancer, only about 30% of patients diagnosed with or whose disease
has progressed to metastatic disease are expected to live five
years following diagnosis.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.6 Approximately
one in five cases of breast cancer is considered
HER2-positive.7
HER2-positive metastatic breast cancer is an aggressive disease
driven by overexpression or amplification of HER2 that affects 15%
to 20% of patients with metastatic breast
cancer.7 While
HER2-targeted therapies have improved outcomes, prognosis remains
poor with most patients experiencing disease progression within two
years of 1st-line treatment with THP, which has been the standard
of care for more than a decade.8,9,10 Further,
approximately one in three patients do not receive any treatment
following 1st-line therapy due to disease progression or
death.11,12
DESTINY-Breast09
DESTINY-Breast09 is a global, multicentre, randomised, open-label,
Phase III trial evaluating the efficacy and safety
of Enhertu (5.4mg/kg) either alone or in combination
with pertuzumab versus standard of care THP as 1st-line treatment
in patients with HER2-positive metastatic breast cancer who had not
received prior chemotherapy or HER2-targeted therapy or had
received neoadjuvant or adjuvant HER2-targeted therapy more than
six months before the diagnosis of advanced or metastatic
disease.
Patients were randomised 1:1:1 to receive
either Enhertu monotherapy with a pertuzumab matching
placebo; Enhertu in combination with pertuzumab; or THP.
Randomisation was stratified by prior treatment
(de
novo metastatic disease
versus progression from early-stage disease), HR status
and PIK3CA mutation status.
The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR
in both the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints
include investigator-assessed PFS, overall survival, overall
response rate, duration of response, pharmacokinetics and safety.
The investigational arm assessing Enhertu monotherapy versus THP remains blinded to
patients and investigators and will continue to the final PFS
analysis.
DESTINY-Breast09 enrolled 1,157 patients across multiple sites in
Africa, 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 the proprietary DXd ADC Technology
of Daiichi Sankyo, 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)
followed by THP is approved in China, India, Singapore, Brazil
and the US as a neoadjuvant treatment for adult patients with
HER2-positive (IHC 3+ or ISH+) Stage II or Stage III breast cancer
based on the results from the DESTINY-Breast11 trial.
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 Brazil, India and the US for the adjuvant treatment for
adult patients with HER2-positive breast cancer who have residual
invasive disease following neoadjuvant trastuzumab (with
or without pertuzumab) and taxane-based treatment based on
the DESTINY-Breast05 trial.
Enhertu (5.4mg/kg) in
combination with pertuzumab is approved in more than 40
countries/regions worldwide as a 1st-line treatment for adult
patients with unresectable or metastatic HER2-positive (IHC 3+ or
ISH+) breast cancer, as determined by a locally or regionally
approved test, based on the results from
the DESTINY-Breast09 trial.
Enhertu (5.4mg/kg) is
approved in more than 100 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 75 countries/regions worldwide for the
treatment of adult patients with unresectable or metastatic hormone
receptor 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, who 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 100 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 80 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 90 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-Gastric04 trials.
Enhertu (5.4mg/kg) is
approved in more than 45 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, DESTINY-CRC02 and/or HERALD trials.
Continued approval in the US for this indication may be contingent
upon verification and description of clinical benefit in a
confirmatory trial.
Enhertu clinical 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 previously treated HER2-positive, HER2-low and
HER2-ultralow metastatic breast cancer, and expanding 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 TROP-2-directed
ADC, Datroway and next-generation oral
SERD, Etcamah (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 Etcamah 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/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Disease, 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. Tolaney SM, et al. Trastuzumab
Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast
Cancer. N Engl J
Med.
2026;394:551-562.
2. de Azambuja E, et
al. Metastatic breast cancer: ESMO Clinical Practice Guideline
for diagnosis, treatment and follow-up. Ann Oncol. 2026;37(9):1203-1219.
3. World Health Organization. Global
Status Report on Cancer 2026. Available
at: https://www.who.int/publications/i/item/9789240123977.
Accessed August 2026.
4. World Health Organization.
Breast Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/20-breast-fact-sheet.pdf.
Accessed August 2026.
5. National Cancer Institute. SEER
Cancer Stat Facts: Female Breast Cancer Subtypes. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed August 2026.
6. Cheng X. A comprehensive
review of HER2 in cancer biology and
therapeutics. Genes (Basel). 2024;15(7):903.
7. Tarantino P, et al. ESMO
expert consensus statements (ECS) on the definition, diagnosis, and
management of HER2-low breast cancer. Ann Oncol. 2023;34(8):645-659.
8. Swain SM, et al. Pertuzumab,
trastuzumab, and docetaxel for HER2-positive metastatic breast
cancer (CLEOPATRA): end-of-study results from a double-blind,
randomised, placebo-controlled, Phase III
study. Lancet
Oncol.
2020;21(4):519-530.
9. Blumenthal G, et
al. First FDA Approval of Dual Anti-HER2 Regimen: Pertuzumab
in Combination with Trastuzumab and Docetaxel for HER2-Positive
Metastatic Breast Cancer. Clin Cancer
Res.
2013;19(18):4911-4916.
10. Tripathy D, et al. De Novo
Versus Recurrent HER2-Positive Metastatic Breast Cancer: Patient
Characteristics, Treatment, and Survival from the SystHERs
Registry. Oncologist. 2020;25(2):e214-e222.
11. Hall
PS, et al. Attrition rates from first- to third-line therapy in
HER2+ metastatic breast cancer in Europe. Presented at SABCS Annual
Meeting 2023. Poster #PO3-16-11.
12. Hartkopf AD, et al. Attrition
in the First Three Therapy Lines in Patients with Advanced Breast
Cancer in the German Real-World PRAEGNANT
Registry. Geburtshilfe
Frauenheilkd. 2024;84(5):459-469.
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:
01 September 2026
|
|
By: /s/
Matthew Bowden
|
|
|
Name:
Matthew Bowden
|
|
|
Title:
Company Secretary
|
