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 2024
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 improved rPFS in advanced prostate cancer
25 November 2024
Truqap combination in PTEN-deficient
metastatic hormone-sensitive
prostate cancer demonstrated statistically significant and
clinically meaningful improvement in radiographic progression-free
survival
in
CAPItello-281 Phase III trial
First and only AKT inhibitor combination to
demonstrate
benefit in this specific subtype of prostate cancer
Positive
high-level results from the CAPItello-281 Phase III trial showed
that AstraZeneca's Truqap (capivasertib) in
combination with abiraterone and androgen deprivation therapy (ADT)
demonstrated a statistically significant and clinically meaningful
improvement in the primary endpoint of radiographic
progression-free survival (rPFS) versus abiraterone and ADT with
placebo in patients with PTEN-deficient de
novo metastatic
hormone-sensitive prostate cancer (mHSPC).
Overall
survival (OS) data were immature at the time of this analysis;
however, the Truqap combination showed an early
trend towards an OS improvement versus abiraterone and ADT
with placebo. The trial will continue as planned to further
assess OS as a key secondary endpoint.
Prostate
cancer is the second most prevalent cancer in men and the fifth
leading cause of male cancer death globally.1 Only one third
of patients with metastatic prostate cancer survive five years
after diagnosis.2 Newly diagnosed
mHSPC is an aggressive form of the disease associated with poor
outcomes and survival.3,4 Approximately
200,000 patients are diagnosed with mHSPC each year, and one
in four have PTEN-deficient tumours.5 Patients with a
tumour biomarker of PTEN deficiency have a particularly poor
prognosis.6
Karim Fizazi, MD, PhD, Institut Gustave Roussy, and University of
Paris Saclay in Villejuif, France, and principal investigator for
the trial said: "Patients with this aggressive form of prostate
cancer with tumour PTEN deficiency currently face a particularly
poor prognosis, and there is an urgent need for new treatments that
improve upon current therapies. The results seen
with capivasertib in combination with
abiraterone-prednisone and androgen deprivation therapy in the
CAPItello-281 trial represent a step forward for these
patients."
Susan
Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "These
results show for the first time, that adding an AKT inhibitor to a
standard-of-care therapy can provide benefit to patients with a
biomarker of PTEN-deficient metastatic hormone-sensitive prostate
cancer. By targeting a key driver of the disease, we have been able
to improve upon current therapies and demonstrate the potential
role of this combination in an area of critical unmet need. It will
be important to see greater maturity in key secondary endpoints
including overall survival."
The safety profile of Truqap in
combination with abiraterone and ADT in CAPItello-281 was broadly
consistent with the known profile of each
medicine.
Data will be presented at a forthcoming medical meeting and shared
with global regulatory authorities.
Notes
Prostate cancer
Prostate
cancer is the second most prevalent cancer in men and the fifth
leading cause of male cancer death globally, with an incidence of
more than 1.4 million and approximately 397,000 deaths in
2022.1
Metastatic
prostate cancer is associated with a significant mortality rate,
with only one third of patients surviving five years after
diagnosis.2 Development of
prostate cancer is often driven by male sex hormones called
androgens, including testosterone.7
Metastatic hormone-sensitive prostate cancer
In
patients with mHSPC, also known as metastatic castration-sensitive
prostate cancer (mCSPC), prostate cancer cells need high levels of
androgens to drive cancer growth.4,7 Hormone
therapies, such as ADT, are widely used to block the action of male
sex hormones and lower the levels of androgens in the
body.4,8 However,
resistance to these therapies is common and there is a need to
extend their use to delay disease progression and castration
resistance, where the prostate cancer grows and spreads to other
parts of the body despite the use of these therapies.3,4,8
In
patients with de
novo mHSPC, the cancer has spread to distant parts of
the body at the time of first diagnosis.9
PTEN-loss
or deficiency fuels the growth of cancer cells, leading to
dysregulation of the PI3K/AKT pathway, and is associated with poor
outcomes in patients with prostate cancer.6,10
CAPItello-281
CAPItello-281 is a Phase III, double-blind, randomised trial
evaluating the efficacy and safety of Truqap in
combination with abiraterone and ADT versus abiraterone and ADT in
combination with placebo in the treatment of patients with
PTEN-deficient de
novo mHSPC.
The global trial enrolled 1,012 adult patients with histologically
confirmed de
novo hormone-sensitive prostate
adenocarcinoma and PTEN deficiency as confirmed by central testing.
The primary endpoint of the CAPItello-281 trial is rPFS as assessed
by investigator, with OS as a secondary
endpoint.
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 the US, EU, Japan and several
other countries for the treatment of adult patients with
HR-positive (or ER-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 also approved in
Australia for the treatment of adult patients with HR-positive,
HER2-negative locally advanced or metastatic breast cancer
following recurrence or progression on or after an endocrine based
regimen based on these trial results.
Truqap is currently being evaluated in Phase III trials
for the treatment of breast cancer (CAPItello-292) and prostate
cancer (CAPItello-280 and CAPItello-281) in combination with
established treatments.
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).
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. 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.
2. Chowdhury S, et al. Real-World Outcomes in
First-Line Treatment of Metastatic Castration-Resistant Prostate
Cancer: The Prostate Cancer Registry. Target
Oncol.
2020;15(3):301-315.
3.
Hussain M, et al. Metastatic Hormone-Sensitive Prostate Cancer and
Combination Treatment Outcomes A Review. JAMA Oncol.
2024;10(6):807-820.
4. American Society of Clinical
Oncology Educational Book. Metastatic Hormone-Sensitive Prostate
Cancer: Toward an Era of Adaptive and Personalized Treatment.
Available at: https://ascopubs.org/doi/pdf/10.1200/EDBK_390166.
Accessed November 2024.
5.
Cerner CancerMPact database. Accessed November 2024.
6. Cuzick J et al. Prognostic value of PTEN loss in
men with conservatively managed localised prostate
cancer. Br J
Cancer. 2013;108(12):2582-2589.
7. National Cancer Institute. Hormone
Therapy for Prostate Cancer Fact Sheet. Available
at: https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet.
Accessed November 2024.
8. Cancer Research UK. Hormone therapy for
metastatic prostate cancer. Available at: https://www.cancerresearchuk.org/about-cancer/prostate-cancer/metastatic-cancer/treatment/hormone-therapy-for-metastatic-prostate-cancer. Accessed
November 2024.
9. McManus H et al. The Past, Present, and Future of
Treatment Intensification for Metastatic Hormone-Sensitive Prostate
Cancer. J Clin
Oncol 2023;
41:3576-3579.
10. Gasmi A et al. Overview of the Development and
Use of Akt Inhibitors in Prostate Cancer. J Clin Med. 2021;11(1):160.
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:
25 November 2024
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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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