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 April 2025
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu combination improved PFS in 1L HER2+ mBC
This announcement contains inside information
22 April 2025
Enhertu plus
pertuzumab demonstrated highly statistically significant and
clinically meaningful improvement in progression-free survival vs.
THP as 1st-line therapy for patients with HER2-positive metastatic
breast cancer
DESTINY-Breast09 Phase III trial of AstraZeneca and Daiichi
Sankyo's Enhertu is the first
trial in more than a decade to demonstrate superior efficacy across
a broad HER2-positive metastatic patient population versus current
1st-line standard of care
Positive high-level results from a planned interim analysis of the
DESTINY-Breast09 Phase III trial showed Enhertu (trastuzumab deruxtecan) in combination with
pertuzumab demonstrated a highly statistically significant and
clinically meaningful improvement in progression-free survival
(PFS) compared to a taxane, trastuzumab and pertuzumab (THP) as a
1st-line treatment for patients with HER2-positive metastatic
breast cancer.
The PFS improvement was seen across all pre-specified patient
subgroups with Enhertu in combination with pertuzumab. The key
secondary endpoint of overall survival (OS) was not mature at the
time of this planned interim analysis; however, interim OS data
showed an early trend favouring the Enhertu combination compared
with THP.
The second arm assessing Enhertu monotherapy versus THP remains blinded to
patients and investigators and will continue to the final PFS
analysis.
HER2-positive metastatic breast cancer is an aggressive disease
driven by overexpression or amplification of HER2 affecting 15-20%
of patients with metastatic breast cancer.1 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.2-4 Further,
approximately one in three patients never go on to receive
treatment following 1st-line therapy due to disease progression or
death.5,6
Susan Galbraith, Executive Vice President, Oncology Haematology
R&D, AstraZeneca, said: "This is the first trial in more than a
decade to demonstrate superior efficacy across a broad
HER2-positive metastatic breast cancer patient population compared
to the current 1st-line standard of care. This is a significant
milestone for patients and sets the foundation
for Enhertu in combination with pertuzumab as an
important treatment option in the first-line HER2-positive
setting."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The
results from DESTINY-Breast09 reinforce the importance of
effectively targeting HER2 to achieve durable disease control early
in the treatment of HER2-positive metastatic breast cancer.
Building on the positive results seen with Enhertu in the second-line setting, these new
findings suggest that starting treatment
with Enhertu in combination with pertuzumab at the time
of metastatic diagnosis delays disease progression, postponing the
time until additional treatment may be needed."
The safety profile of Enhertu in combination with pertuzumab was
consistent with the known profiles of each individual
therapy.
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 the combination arm of DESTINY-Breast09 will be
presented at an upcoming medical meeting and shared with
regulatory authorities.
Enhertu is already
approved in more than 75 countries as 2nd-line treatment for
patients with HER2-positive breast cancer based on the results from
the DESTINY-Breast03 trial.
Notes
HER2-positive metastatic breast cancer
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.7 More
than two million breast
cancer cases were diagnosed in 2022, with more than 665,000 deaths
globally.7 While
survival rates are high for those diagnosed with early breast
cancer, only about 30% of patients diagnosed with or who progress
to metastatic disease are expected to live five years following
diagnosis.8
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including breast
cancer.9 HER2
protein overexpression may occur as a result of HER2 gene
amplification and is often associated with aggressive disease in
breast cancer.1 Approximately
one in five cases of breast cancer are considered
HER2-positive.10
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.2-4 Further,
approximately one in three patients never go on to receive
treatment following 1st-line therapy due to disease progression or
death.5,6
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 (a taxane [docetaxel or
paclitaxel], trastuzumab and pertuzumab) as a 1st-line treatment in
patients with HER2-positive metastatic breast
cancer.
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), hormone receptor (HR)
status and PIK3CA mutation status.
The primary endpoint of DESTINY-Breast09 is PFS as assessed by
blinded independent central review in both
the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints
include investigator-assessed PFS, overall survival, objective
response rate, duration of response, investigator-assessed time to
second progression or death, patient-reported tolerability,
pharmacokinetics and safety.
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 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 may be
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 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 TROP-2-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
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. 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.
2. 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 3
study. Lancet
Oncol. 2020;21(4):519-530.
3. 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 Can
Res. 2013;19(18).
4. 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.
5.
Hall P, 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.
6. Hartkopt 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.
7. 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.
8. National Cancer Institute.
SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html Accessed
April 2025.
9. Iqbal N, et al. Human Epidermal Growth
Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int.
2014;852748.
10. 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.
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:
22 April 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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