astrazenecaplc3089m
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
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United
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Truqap recommended for EU breast cancer approval
29 April 2024
Truqap plus Faslodex recommended
for approval in the EU by CHMP for
patients with advanced ER-positive
breast
cancer
Recommendation based on CAPItello-291 results which showed the
Truqap combination reduced the risk of disease
progression or death by 50%
vs. Faslodex standard of care in a biomarker-altered
population
AstraZeneca's Truqap (capivasertib)
in combination with Faslodex (fulvestrant) has
been recommended for
approval in the European Union (EU) for the
treatment of
adult patients with estrogen receptor (ER)-positive, HER2-negative
locally advanced or metastatic breast cancer with one or more
PIK3CA, AKT1, or PTEN-alterations following
recurrence or progression on or after an endocrine-based
regimen.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) based its positive opinion
on the
results from the CAPItello-291 Phase
III trial published
in The
New England Journal of Medicine.1
In the trial, Truqap in
combination with Faslodex reduced
the risk of disease progression or death by 50%
versus Faslodex alone
in patients with tumours harbouring PI3K, AKT or PTEN
alterations (based on hazard ratio of 0.50,
95% confidence interval 0.38-0.65; p=<0.001; median
progression-free survival (PFS) 7.3 versus 3.1
months).1
In Europe, breast cancer remains the leading cause of cancer death,
with more than 140,000 deaths in 2022 and more than 550,000 new
patients diagnosed in the same year.2 HR-positive
breast cancer (expressing
estrogen or progesterone receptors, or
both), is the most common subtype of
breast cancer with 70% of tumours considered HR-positive and
HER2-low or HER2-negative.3 More
than 97% of HR-positive breast cancer
tumours are ER-positive.4,5 Collectively,
mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently,
affecting approximately 50% of patients with advanced HR-positive
breast cancer.6-8 HR-positive
breast cancer progression is often driven by estrogen receptors,
and endocrine therapies that target ER-driven disease are widely
used as 1st-line treatment in the advanced setting, and often
paired with CDK4/6 inhibitors.9-11 However,
resistance to these therapies develops in many patients with
advanced disease, and alternative approaches are needed to extend
the effectiveness of endocrine-based therapies.10
Mafalda Oliveira, MD, PhD, Senior Consultant at
the Department of Medical Oncology,
Vall d'Hebron University Hospital, and Senior Clinical Investigator
of the Vall d'Hebron Institute of Oncology's (VHIO) Breast Cancer
Group in Barcelona, Spain, said: "There is an urgent need to extend
the effectiveness of widely used endocrine therapies in patients
with advanced ER-positive breast cancer to delay disease
progression or resistance. With this combination
demonstrating a fifty per cent reduction in disease progression or
death in patients with tumours harbouring PIK3CA, AKT1, or
PTEN-alterations in the CAPItello-291 trial, this positive
recommendation marks an important step in providing a much-needed
new treatment option for approximately half of patients in this
setting with these specific tumour biomarkers."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Today's news reinforces the practice-changing
potential of Truqap in
combination with Faslodex to
extend the effectiveness of endocrine-based treatment approaches
for patients who experience tumour progression on, or resistance to
widely used endocrine-based therapies. This
recommendation recognises
the high unmet need in this biomarker-specific patient population,
and if approved, patients in Europe with
this specific type of disease may
be able to benefit from this first-in-class
treatment option."
In the CAPItello-291 trial, the safety profile
of Truqap plus Faslodex was
similar to that observed in previous trials evaluating this
combination.1
Regulatory applications are currently under review in China and
several other countries, and similar indications
for Truqap in
combination with Faslodex are
already approved in Japan,
the US and
several other countries based on results from the CAPItello-291
trial.
Notes
HR-positive breast cancer
In Europe, breast cancer remains the leading cause of cancer death,
with more than 140,000 deaths in 2022 and more than 550,000 new
patients diagnosed in the same year.2
HR-positive breast cancer (expressing
estrogen or progesterone receptors, or
both), is the most common subtype of
breast cancer with 70% of tumours considered HR-positive and
HER2-low or HER2-negative.3
HR-positive breast cancer progression is often driven by estrogen
receptors, and endocrine therapies that target ER-driven disease
are widely used as 1st-line treatment in the advanced setting, and
often paired with CDK4/6 inhibitors.9-11 However,
resistance to CDK4/6 inhibitors and current endocrine therapies
develops in many patients with advanced disease.10 Once
this occurs, treatment options are limited - with chemotherapy
being the current standard of care - and survival rates are low with
approximately 35% of patients anticipated to live beyond five years
after diagnosis.3,10,12
The optimisation of endocrine therapy and overcoming
resistance to enable patients to continue benefiting from these
treatments, as well as identifying new therapies for those who are
less likely to benefit, are active areas of focus for breast cancer
research.
CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial
evaluating the efficacy of Truqap in
combination with Faslodex versus
placebo plus Faslodex for
the treatment of locally advanced (inoperable) or metastatic
HR-positive (ER-positive and ER-positive, progesterone
receptor-positive), HER2-low or negative (immunohistochemistry
(IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative)
breast cancer.
The global trial enrolled 708 adult patients with histologically
confirmed HR-positive, HER2-low or negative breast cancer whose
disease has recurred or progressed during or after aromatase
inhibitor therapy, with or without a CDK4/6 inhibitor, and up to
one line of chemotherapy for advanced disease. The trial has dual
primary endpoints of PFS in the overall patient population and in a
population of patients whose tumours have qualifying alterations in
the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial,
approximately 40% of tumours had these alterations and
approximately 70% of patients received a prior CDK4/6
inhibitor.
Truqap
Truqap is a first-in-class, potent,
adenosine triphosphate (ATP)-competitive inhibitor of all three AKT
isoforms (AKT1/2/3). Truqap 400mg
is administered twice daily according to an intermittent dosing
schedule of four days on and three days off. This was chosen in
early phase trials based on tolerability and the degree of target
inhibition.
Truqap is approved in Japan, the US and
several other countries for the treatment of adult patients with
HR-positive, HER2-negative locally advanced or metastatic breast
cancer with one or more biomarker alterations (PIK3CA, AKT1 or
PTEN) following recurrence or progression on or after an
endocrine-based regimen based on the results from the CAPItello-291
trial.
Truqap is currently being evaluated in
Phase III trials for the treatment of multiple subtypes of breast
cancer and in other tumour types in combination with established
treatments. The ongoing clinical research programme is focused on
tumours reliant on signalling via the PI3K/AKT pathway, and in
tumours harbouring biomarker alterations in this
pathway.
Truqap was discovered by AstraZeneca
subsequent to a collaboration with Astex Therapeutics (and its
collaboration with the Institute of Cancer Research and Cancer
Research Technology Limited).
Faslodex
Faslodex is an endocrine therapy indicated
for the treatment of estrogen receptor-positive, locally advanced
or metastatic breast cancer in postmenopausal women not previously
treated with endocrine therapy, or with disease relapse on or after
adjuvant anti-estrogen therapy, or disease progression on
anti-estrogen therapy.
In the US, EU and Japan,
Faslodex is also approved in combination
with CDK4/6 inhibitors for the treatment of women with HR-positive,
HER2-negative advanced or metastatic breast cancer, whose cancer
has progressed after endocrine medicine.
Faslodex represents a hormonal treatment
approach that helps to slow tumour growth by blocking and degrading
the estrogen receptor - a key driver of disease
progression.
Faslodex is approved as monotherapy or in
combination with medicines from various drug classes including
CDK4/6, PI3K and AKT inhibitors for the treatment of patients with
HR-positive advanced breast cancer and is being evaluated in
combination with medicines from other drug
classes.
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. Turner
N, et al. Capivasertib in Hormone Receptor-Positive Advanced Breast
Cancer. NEJM.
2023; 388:2058-70.
2. World Health
Organization. GLOBOCAN Europe Fact Sheet. Available
at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf.
Accessed April 2024.
3. National
Cancer Institute. Surveillance, Epidemiology and End Results
Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed April 2024.
4.
Bae S, et al. Poor
prognosis of single hormone receptor positive breast cancer:
similar outcome as triple-negative breast
cancer. BMC
Cancer. 2015;
15:138.
5.
Cserni G, et al.
Estrogen Receptor Negative and Progesterone Receptor Positive
Breast Carcinomas-How Frequent are they? Pathol.
Oncol. Res. 2011;
17:663-668.
6. Howell
S J, et al. Fulvestrant plus capivasertib versus placebo after
relapse or progression on an aromatase inhibitor in metastatic,
oestrogen receptor-positive, HER2-negative breast cancer
(FAKTION). J
Clin Oncol. 2022;
23:851-64.
7. Hortobagyi
G N, et al. Correlative
Analysis of Genetic Alterations and Everolimus Benefit in Hormone
Receptor-Positive, Human Epidermal Growth Factor Receptor
2-Negative Advanced Breast Cancer: Results From
BOLERO-2. J
Clin Oncol. 2016;
34:419-26.
8. Millis
S Z, et al. Landscape of phosphatidylinositol-3-kinase pathway
alterations across 19784 diverse solid
tumors. JAMA
Oncol. 2016;2(12):1565-73.
9.
Lin M, et al.
Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine
Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive,
HER2-negative metastatic breast cancer. J
Cancer. 2020;
10.7150/jca.48944.
10. Lloyd
M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced
Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging
Therapeutic Opportunities. Clin
Cancer Res. 2022;
28(5):821-30.
11. Scabia V, et al. Estrogen receptor positive breast
cancers have patient specific hormone sensitivities and rely on
progesterone receptor. Nat
Commun. 2022;
10.1038/s41467-022-30898-0.
12. National Comprehensive Cancer Network. Clinical Practice
Guidelines in Oncology (NCCN Guidelines). Available
at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. Accessed
April 2024
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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