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 2024
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 improved PFS in HER2-low and ultralow
29 April 2024
Enhertu demonstrated
statistically significant and clinically meaningful improvement in
progression-free survival in HR-positive, HER2-low metastatic
breast cancer following one or more lines of endocrine therapy in
DESTINY-Breast06 Phase III trial
AstraZeneca and Daiichi Sankyo's Enhertu
also demonstrated a clinically
meaningful progression-free survival
improvement
in patients with HER2-ultralow expression
Positive high-level results from the DESTINY-Breast06 Phase III
trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a
statistically significant and clinically meaningful
improvement in progression-free survival (PFS) compared to
standard-of-care chemotherapy in the primary trial population of
patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic
breast cancer following one or more lines of endocrine
therapy.
A statistically significant and clinically meaningful improvement
in PFS was also observed in the overall trial population (patients
with HER2-low and HER2-ultralow [defined as IHC 0 with membrane
staining; IHC >0<1+] metastatic breast cancer). A
prespecified subgroup analysis showed the clinically
meaningful improvement was consistent between patients with
HER2-low and HER2-ultralow expression.
Overall survival (OS) data were not mature at the time of the
analysis; however, Enhertu showed an early trend towards an OS
improvement versus standard-of-care chemotherapy in patients with
HER2-low metastatic breast cancer and in the overall trial
population. The trial will continue as planned to further assess OS
and other secondary endpoints.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "DESTINY-Breast06 shows
that Enhertu could become a new standard of care for
patients with HER2-low and HER2-ultralow metastatic breast cancer
following one or more lines of endocrine therapy. These data
underscore the potential for treatment
with Enhertu across
the spectrum of HR-positive breast cancer, further redefining the
treatment of metastatic breast cancer."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The
topline results from DESTINY-Breast06 highlight the importance of
continuing to challenge current treatment paradigms and
established breast cancer classifications to evolve how we
treat patients with HR-positive, HER2-expressing metastatic breast
cancer. Building on the practice-changing data seen in
DESTINY-Breast04, these results reinforce the potential for use
of Enhertu earlier in the treatment landscape and
in an even broader patient population."
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.
It is estimated that approximately 60-65% of HR-positive,
HER2-negative breast cancers are HER2-low and potentially an
additional 25% may be HER2-ultralow.1,2 Endocrine
therapies are widely used in the early lines of treatment
for HR-positive metastatic breast cancer; however after two
lines of treatment, further efficacy from endocrine therapy is
often limited.3 The current
standard of care following endocrine therapy is chemotherapy, which
is associated with poor response rates and
outcomes.3-6
The safety profile of Enhertu was consistent with previous breast cancer
clinical trials with no new safety signals
identified.
The data will be presented at a forthcoming medical meeting and
shared with global regulatory authorities.
Notes
DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III
trial evaluating the efficacy and safety
of Enhertu (5.4
mg/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 (defined
as IHC 0 with membrane staining; IHC >0<1+) advanced or
metastatic breast cancer. Patients in the trial had no prior
chemotherapy for advanced or metastatic disease and
either experienced disease progression within 6 months of
starting 1st-line treatment with an endocrine therapy combined with
a CDK4/6 inhibitor or received at least two previous
lines of endocrine therapies in the metastatic
setting.
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 OS in patients with
HER2-low expression and PFS by BICR and OS in the overall trial
population (HER2-low and HER2-ultralow). 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. Analysis of the HER2-ultralow
subgroup was not powered to demonstrate statistical
significance.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and
n=153 for HER2-ultralow) at multiple sites in Asia, Europe, North
America and South America. For more information about the trial,
visit ClinicalTrials.gov.
Breast cancer and HER2 expression
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 approximately 30% of patients who are diagnosed with
or progress to metastatic disease are expected to live five years
after their diagnosis.8
HR-positive, HER2-negative is the most common breast cancer
subtype, accounting for approximately 70% of all breast
cancers.8 HER2
is a tyrosine kinase receptor growth-promoting protein expressed on
the surface of many types of tumours, including breast
cancer.9 Patients
with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are
classified as HER2-positive and treated with HER2-targeted
therapies, representing approximately 15-20% of all breast
cancers.10 Historically,
tumours that were not classified as HER2-positive were classified
as HER2-negative; however, many of these tumours still carry some
level of HER2 expression.11 It
is estimated that approximately 60-65% of HR-positive,
HER2-negative breast cancers are HER2-low and potentially an
additional 25% may be HER2-ultralow.1,2
Prior to the approval of Enhertu in HER2-low metastatic breast cancer post
chemotherapy based on the DESTINY-Breast04 trial, there were no
targeted therapies approved specifically for patients with HER2-low
expression.12 There
are no targeted therapies specifically approved for patients with
HER2-ultralow expression.
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 (5.4
mg/kg) is approved in more than 60 countries for the treatment
of adult patients with unresectable or metastatic HER2-positive
(IHC 3+ or 2+/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 (5.4 mg/kg) is
approved in more than 60 countries for the treatment of adult
patients with unresectable or metastatic HER2-low (IHC 1+ or
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 more than 35 countries for the treatment of
adult patients with unresectable or metastatic 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 trial.
Continued approval in the US for this indication may be contingent
upon verification and description of clinical benefit in a
confirmatory trial.
Enhertu (6.4 mg/kg) is
approved in more than 40 countries 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 and/or DESTINY-Gastric02 trials.
Enhertu (5.4 mg/kg) is
approved in the US for the treatment of adult patients with
unresectable or metastatic HER2-positive (IHC 3+) solid tumours who
have received prior systemic treatment and who have no satisfactory
alternative treatment options based on results from
the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
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 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 datopotamab
deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge, and redefine, 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 (trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are
aiming to improve outcomes in previously treated HER2-positive and
HER2-low 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 and Zoladex (goserelin) and aims to reshape the
HR-positive space with first-in-class AKT
inhibitor, Truqap, and next-generation SERD and potential new
medicine camizestrant. AstraZeneca is also collaborating with
Daiichi Sankyo to explore the potential of TROP2-directed ADC,
datopotamab deruxtecan, in this setting.
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.
To bring much-needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is evaluating the potential of datopotamab deruxtecan
alone and in combination with
immunotherapy Imfinzi (durvalumab), Truqap in
combination with chemotherapy, and Imfinzi in combination with other oncology
medicines, including Lynparza and Enhertu.
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 operates in over
100 countries and its innovative medicines are 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. Denkert C, et al. Clinical and
molecular characteristics of HER2-low-positive breast cancer:
pooled analysis of individual patient data from four prospective,
neoadjuvant clinical trials. Lancet
Oncol. 2021
Aug;22(8):1151-1161.
2. Chen Z, et al. Is HER2
ultra-low breast cancer different from HER2 null
or HER2 low breast cancer? A study of 1363
patients. Breast Cancer Res
Treat. 2023
Nov;202(2):313-323.
3. Manohar P, et al. Updates in
endocrine therapy for metastatic breast
cancer. Cancer Biol
Med. 2022 Feb 15;
19(2):202-212.
4. 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.
5. 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.
6. 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.
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 Apr 4. doi:
10.3322/caac.21834.
8. National Cancer Institute.
Surveillance, Epidemiology and End Results Program. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed April 2024
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. 2020;54(1):34-44.
11. Sajjadi E, et al. Improving HER2 testing
reproducibility in HER2-low breast cancer. Cancer Drug
Resist. 2022;5(4):882-888.
12. Modi S, et al. Trastuzumab Deruxtecan in
Previously Treated HER2-Low Advanced Breast
Cancer. N Engl J
Med. 2022;387:9-20.
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:
29 April 2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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