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 November 2023
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.Truqap approved in US for HR+ breast cancer
17
November 2023
Truqap (capivasertib)
plus Faslodex approved
in the US for patients with advanced HR-positive
breast
cancer
First-in-class AKT inhibitor has potential to reshape treatment for
breast cancer patients with specific biomarker alterations (PIK3CA,
AKT1 or PTEN)
Approval based on CAPItello-291 results which showed this
combination reduced the risk of disease progression or death by 50%
vs. Faslodex alone in the biomarker-altered population
AstraZeneca's Truqap (capivasertib)
in combination with Faslodex (fulvestrant) has
been approved in the US for the treatment of adult patients
with hormone receptor (HR)-positive, HER2-negative locally advanced
or metastatic breast cancer with one or more biomarker alterations
(PIK3CA, AKT1 or PTEN). Eligible patients will have progressed on
at least one endocrine-based regimen in the metastatic setting or
experienced recurrence on or within 12 months of completing
adjuvant therapy.
The approval by the Food and Drug Administration (FDA) was based on
the results from the CAPItello-291 Phase
III trial published earlier this year
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 pathway biomarker
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).
Breast
cancer is the most common cancer and one of the leading causes of
cancer-related death worldwide.2 HR-positive
breast cancer (expressing
estrogen or progesterone receptors, or
both), is the most common
subtype, with more than 65% of tumours considered HR-positive and
HER2-low or HER2-negative.3 Collectively,
mutations in PIK3CA, AKT1 and alterations in PTEN occur
frequently, affecting up to 50% of patients with advanced
HR-positive breast cancer.4-6 Endocrine
therapies are widely used in this setting, but many patients
develop resistance to 1st-line cyclin-dependent kinase (CDK)
4/6 inhibitors and estrogen receptor-targeting therapies,
underscoring the need for additional endocrine therapy-based
options.7
Komal
Jhaveri, MD, Medical Oncologist, Memorial Sloan Kettering Cancer
Center (MSK), US, said: "Patients with advanced HR-positive breast
cancer typically experience tumour progression or resistance with
widely used first-line endocrine therapies and there is an urgent
need to extend the effectiveness of these approaches. The
combination of capivasertib and
fulvestrant, a first-of-its-kind combination, provides a
much-needed new treatment option for up to half of patients in this
setting with these specific biomarkers, offering the potential to
delay disease progression and provide more time with their disease
under control."
Dave
Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "The rapid US approval of Truqap reinforces the
important role of the PI3K/AKT pathway in HR-positive breast cancer
and the critical need to test patients at the time of diagnosis, as
up to fifty per cent have tumours with these alterations. As a
first-in-class medicine, this approval provides a critical new
option for patients in the US with this specific type of disease
and we look forward to bringing Truqap to the many breast cancer
patients who can benefit across the globe."
In
the CAPItello-291 trial, the safety profile
of Truqap plus Faslodex was similar to that
observed in previous trials evaluating this
combination.1
Concurrently
with this approval, the FDA also approved a companion diagnostic
test to detect relevant alterations (PIK3CA, AKT1 and
PTEN).
The US
regulatory submission was granted Priority
Review and reviewed under Project Orbis, which provides
a framework for concurrent submission and review of oncology
medicines among participating international partners. As part of
Project Orbis, Truqap plus Faslodex is also under
review by regulatory authorities in Australia, Brazil,
Canada, Israel, Singapore, Switzerland and the UK.
Regulatory
applications for Truqap in
combination with Faslodex are
also currently under review in China, the European Union, Japan and
several other countries.
Financial considerations
Following
this approval in the US, Astex Therapeutics is eligible to receive
a milestone payment from AstraZeneca on first commercial sale of
the drug in the US as well as royalties on future sales in line
with the agreement between the two companies.
Notes
HR-positive breast cancer
Breast
cancer is the most common cancer and one of the leading causes of
cancer-related death worldwide.2 More than two
million patients were diagnosed with breast cancer in 2020, with
nearly 685,000 deaths globally.2 In the US, more
than 290,000 patients are expected to be diagnosed in 2023, with
more than 43,000 deaths.8
HR-positive
breast cancer (expressing
estrogen or progesterone receptors, or
both), is the most common subtype
of breast cancer with more than 65% of tumours considered
HR-positive and HER2-low or HER2-negative.3 Collectively,
mutations in PIK3CA, AKT1 and alterations in
PTEN occur frequently, affecting up to 50% of patients with
advanced HR-positive breast cancer.4-6
The growth of HR-positive breast cancer cells is often driven by
estrogen receptors (ER), andendocrine therapies that target
ER-driven disease are widely used as first-line treatment in the
advanced setting, and often paired with CDK4/6
inhibitors.7,9,10 However,
resistance to CDK4/6 inhibitors and current endocrine therapies
develops in many patients with advanced disease.9 Once
this occurs, treatment options are limited - with chemotherapy
being the current standard of care - and survival rates are low with 30%
of patients anticipated to live beyond five years after
diagnosis.3,9,11
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, 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 (capivasertib) 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 currently being evaluated in Phase III trials
for the treatment of multiple subtypes of breast cancer and in
other tumour types either as monotherapy or 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. Sung H, et al. Global Cancer Statistics 2020:
GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36
Cancers in 185 Countries. CA Cancer J
Clin. 2021;
10.3322/caac.21660.
3. National Cancer Institute. Surveillance,
Epidemiology and End Results Program. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed
November 2023.
4. 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.
5. 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.
6. Millis S Z, et al. Landscape of
phosphatidylinositol-3-kinase pathway alterations across 19784
diverse solid tumors. JAMA
Oncol. 2016;2(12):1565-73.
7. 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.
8. American Cancer Society. Key
Statistics for Breast Cancer. Available at: https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html.
Accessed November 2023.
9. 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.
10. 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.
11. 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
November 2023.
Dr. Jhaveri has financial interests related to
AstraZeneca.
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:
17 November 2023
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|
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