REG - AstraZeneca PLC - Truqap improved rPFS in advanced prostate cancer

AstraZenecaAnnouncement

25/11/2024 07:00

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RNS Number : 4103N  AstraZeneca PLC  25 November 2024

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
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Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
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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
(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
(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
(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

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