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 February 2025
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu recommended in EU in post-ET breast cancer
28 February 2025
Enhertu recommended
for approval in the EU by CHMP for patients with HER2-low or
HER2-ultralow metastatic breast cancer following at least one
endocrine therapy
Recommendation based on DESTINY-Breast06 Phase III trial
results which
showed Enhertu demonstrated superiority vs. chemotherapy with a
median progression-free survival of more than one
year
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab
deruxtecan) has
been recommended for approval in the European Union
(EU) as a monotherapy for the treatment
of adult patients with unresectable or metastatic hormone receptor
(HR)-positive, HER2-low or HER2-ultralow breast cancer who have
received at least one endocrine therapy in the metastatic
setting and
who are not considered suitable for endocrine therapy as the next
line of treatment.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) based its positive opinion on the
results from the DESTINY-Breast06 Phase III trial, which were
presented at the 2024 American Society of Clinical Oncology (ASCO)
Meeting and published in The
New England Journal of Medicine.
In the trial, Enhertu showed
a 38% reduction in the risk of disease progression or death versus
chemotherapy (hazard ratio [HR] 0.62; confidence interval [CI]
0.52-0.75; p<0.0001) in patients with chemotherapy-naïve
HR-positive, HER2-low metastatic breast cancer with a median
progression-free survival (PFS) of 13.2 months versus 8.1
months.
In the overall trial population (patients with HER2-low or
HER2-ultralow metastatic breast cancer), the median PFS was 13.2
months in patients randomised to Enhertu compared
to 8.1 months in those randomised to chemotherapy (HR 0.64; 95% CI
0.54-0.76; p<0.0001). In an exploratory analysis, results
were seen to be consistent between patients with HER2-low
expression and HER2-ultralow expression.
Susan Galbraith, Executive Vice President, Oncology Haematology
R&D, AstraZeneca, said: "Endocrine therapy is typically used in
the initial treatment of HR-positive metastatic breast cancer but
as the disease progresses the benefit of continued endocrine
therapy is limited, and subsequent standard-of-care chemotherapy is
associated with poor outcomes. Enhertu has
the potential to be the first HER2-directed treatment for patients
in the EU with HR-positive, HER2-low or HER2-ultralow metastatic
breast cancer directly following endocrine therapy, which would
mark an important shift in how patients in this setting are
treated."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said:
"Enhertu is
the first HER2-directed treatment and antibody drug conjugate to
show a progression-free survival of more than one year in patients
with HER2-low or HER2-ultralow metastatic breast cancer following
endocrine therapy. The CHMP recommendation is encouraging and
supports our goal of further developing and advancing the way
breast cancer is classified and treated."
HER2 status in the trial was confirmed by a central laboratory and
was performed on a tumour sample obtained at the time of initial
metastatic diagnosis or later. Approximately 85-90% of patients
with HR-positive, HER2-negative metastatic breast cancer were
determined to be HER2-low or HER2-ultralow.1
The safety profile of Enhertu in DESTINY-Breast06 was consistent with
previous clinical trials of Enhertu in
breast cancer 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.
Enhertu was
recently approved
in the US for patients with HR-positive,
HER2-low or HER2-ultralow metastatic breast cancer that has
progressed on one or more endocrine therapies in the metastatic
setting. In addition to the EU, regulatory applications are under
review in Japan and several other countries based on the
DESTINY-Breast06 results.
Enhertu is already
approved in more than 75 countries, including the EU, for patients
with HER2-low metastatic breast cancer who have received prior
chemotherapy 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.
Notes
Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.2 More
than two million breast cancer cases were diagnosed in 2022 with
more than 665,000 deaths globally.2 In
Europe, approximately 557,000 cases of breast cancer are diagnosed
annually.3 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.4
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including breast
cancer.5 Patients
with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are
classified as HER2-positive and treated with HER2-directed
therapies, representing approximately 15-20% of all breast
cancers.6 Historically,
tumours that were not classified as HER2-positive were classified
as HER2-negative.7
HR-positive, HER2-negative is the most common breast cancer
subtype, accounting for approximately 70% of all breast
cancers.4 Endocrine
therapies are widely given consecutively in the early lines of
treatment for HR-positive metastatic breast cancer. However, after
initial treatment, further efficacy from endocrine therapy is often
limited.8 The
current standard of care following endocrine therapy is
chemotherapy, which is associated with poor response rates and
outcomes.8-11
Despite being classified as HER2-negative, many of these tumours
may still carry some level of HER2 expression.7 In
the DESTINY-Breast06 trial, approximately 85-90% of patients with
HR-positive, HER2-negative metastatic breast cancer were determined
to be HER2-low or HER2-ultralow.1
Prior to the approval of Enhertu in HER2-low metastatic breast cancer based
on the DESTINY-Breast04 trial, there were no targeted therapies
specifically approved for patients with HER2-low expression. There
are no targeted therapies specifically approved in the EU for
patients with HER2-ultralow expression.12,13
DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III
trial evaluating the efficacy and safety of Enhertu (5.4mg/kg)
versus investigator's choice of chemotherapy (capecitabine,
paclitaxel or nab-paclitaxel) in patients with HR-positive,
HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane
staining) advanced or metastatic breast cancer. Patients in the
trial had no prior chemotherapy for advanced or metastatic disease
and received at least two lines of prior endocrine therapy in the
metastatic setting. Patients were also eligible if they had
received one prior line of endocrine therapy combined with a CDK4/6
inhibitor in the metastatic setting and experienced disease
progression within six months of starting 1st-line treatment or
received endocrine therapy as an adjuvant treatment and experienced
disease recurrence within 24 months.
The primary endpoint is PFS in the HR-positive, HER2-low patient
population as measured by blinded independent central review
(BICR). Key secondary endpoints include PFS by BICR in the overall
trial population (HER2-low and HER2-ultralow), overall survival
(OS) in the HER2-low patient population and OS in the overall trial
population. Other secondary endpoints include objective response
rate, duration of response, time to first subsequent treatment or
death, time to second subsequent treatment or death and
safety.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and
n=153 for HER2-ultralow) in Asia, Europe, Australia, 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 (5.4
mg/kg) is approved in the US for adult patients with unresectable
or metastatic HR-positive, HER2-low (IHC 1+ or
IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane
staining) breast cancer, as determined by an FDA-approved test,
that has 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, Russia, Israel and Brazil 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. Salgado RF, et al. LBA21 - Human
epidermal growth factor receptor 2 (HER2)-low and HER2-ultralow
status determination in tumors of patients (pts) with hormone
receptor-positive (HR+) metastatic breast cancer (mBC) in
DESTINY-Breast06 (DB-06). Annals of
Oncology. (2024) 35 (suppl_2):
1-72. 10.1016/annonc/annonc1623.
2. 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 Apr 4. doi:
10.3322/caac.21834.
3. WHO.
International Agency of Cancer Research. Cancer Today. Breast.
2022. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/20-breast-fact-sheet.pdf.
Accessed February 2025.
4. National Cancer Institute.
Surveillance, Epidemiology and End Results
Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed
February 2025.
5. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
6. Ahn S, et al. HER2 status in breast
cancer: changes in guidelines and complicating factors for
interpretation. J Pathol Transl
Med. 2020;54(1):34-44.
7. Sajjadi E, et al. Improving HER2
testing reproducibility in HER2-low breast
cancer. Cancer Drug
Resist. 2022;5(4):882-888.
8. Manohar P, et al. Updates in
endocrine therapy for metastatic breast
cancer. Cancer Biol
Med. 2022 Feb 15;
19(2):202-212.
9. Cortes J, et al. Eribulin
monotherapy versus treatment of physician's choice in patients with
metastatic breast cancer (EMBRACE): a phase 3 open-label randomised
study. Lancet. 2011;377:914-923.
10. Yuan P, et al. Eribulin mesilate versus
vinorelbine in women with locally recurrent or metastatic breast
cancer: A randomised clinical trial. Eur J
Cancer.
2019;112:57-65.
11. Jerusalem G, et al. Everolimus Plus
Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen
Receptor-Positive, HER2-Negative Advanced Breast
Cancer. JAMA Oncol. 2018;4(10):1367-1374.
12. Modi S, et al. Trastuzumab Deruxtecan in
Previously Treated HER2-Low Advanced Breast
Cancer. N Engl J
Med. 2022;387:9-20.
13. Bardia A, et al. Trastuzumab Deruxtecan
after Endocrine Therapy in Metastatic Breast
Cancer. N Eng J Med. 2024; 391:2110-2122.
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.
Date:
28 February 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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