REG - AstraZeneca PLC - Capivasertib Phase III trial met primary endpoints

AstraZenecaAnnouncement

26/10/2022 07:17

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20221026:nRSZ1531Ea&default-theme=true

RNS Number : 1531E  AstraZeneca PLC  26 October 2022

26 October 2022 07:00 BST

 

Capivasertib plus Faslodex significantly improved progression-free survival
vs. Faslodex in CAPItello-291 Phase III trial in advanced HR-positive breast
cancer

 

Capivasertib, a potential first-in-class AKT inhibitor, combined with Faslodex
could become a new option for patients in this setting regardless of biomarker
status

 

Positive high-level results from the CAPItello-291 Phase III trial showed that
AstraZeneca's capivasertib in combination with Faslodex (fulvestrant)
demonstrated a statistically significant and clinically meaningful improvement
in progression-free survival (PFS) versus placebo plus Faslodex in patients
with hormone receptor (HR)-positive, human epidermal growth factor receptor 2
(HER2)-low or negative locally advanced or metastatic breast cancer, following
recurrence or progression on or after endocrine therapy (with or without a
CDK4/6 inhibitor).

 

The trial met both primary endpoints, improving PFS in the overall patient
population and in a prespecified biomarker subgroup of patients whose tumours
had qualifying alterations in the PIK3CA, AKT1 or PTEN genes. Although the
overall survival (OS) data were immature at the time of the analysis, early
data are encouraging. The trial will continue to assess OS as a key secondary
endpoint.

 

The safety profile of capivasertib plus Faslodex was similar to that observed
in previous trials evaluating this combination.

 

Breast cancer is the most common cancer worldwide, with an estimated 2.3
million patients diagnosed in 2020.(1) Approximately 70% of breast cancer
tumours are considered HR-positive and HER2-low or negative.(2) Endocrine
therapies are widely used for the treatment of HR-positive breast cancer, but
many patients with advanced disease develop resistance to 1st-line CDK4/6
inhibitors and estrogen receptor-targeting therapies, underscoring the need
for additional options.(3)

 

Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of
Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London,
UK, and principal investigator in the CAPItello-291 Phase III trial, said:
"The CAPItello-291 Phase III trial results show capivasertib offers a
clinically meaningful improvement in progression free survival for patients
with HR-positive breast cancer. This potential new medicine could give people
more time with their cancer under control, which is a priority for patients
and their families."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "These exciting data in an all-comers population indicate that
capivasertib could become a new first-in-class treatment option for patients
with HR-positive breast cancer. These patients often experience tumour
progression on, or resistance to, available endocrine therapies for advanced
disease and urgently need new therapies that extend the effectiveness of
endocrine-based treatment approaches."

 

The data will be presented at a forthcoming medical meeting and shared with
global health authorities.

 

AstraZeneca has a comprehensive portfolio of approved and potential new
medicines in development for patients with breast cancer. In addition to these
results, the Company is also announcing today results from the SERENA-2 Phase
II trial (https://www.astrazeneca.com/media-centre/press-releases.html) of
camizestrant, the next-generation oral selective estrogen receptor degrader
(ngSERD) in advanced estrogen receptor (ER)-positive breast cancer.

 

Notes

 

HR-positive breast cancer

HR-positive breast cancer (expressing estrogen or progesterone receptors, or
both), is the most common subtype of breast cancer, and the growth of
HR-positive breast cancer cells is often driven by ER.(2,4,5) Endocrine
therapies that target ER-driven disease are widely used as 1st-line treatment
for this form of breast cancer in the advanced setting, and often paired with
cyclin-dependent kinase (CDK) 4/6 inhibitors. However, resistance to CDK4/6
inhibitors and current endocrine therapies develops in many patients with
advanced disease and treatment options are limited.(3) Optimising endocrine
therapy and overcoming resistance for patients with ER-driven disease at all
stages of treatment are active areas of focus for breast cancer research.

 

CAPItello-291

CAPItello-291 is a Phase III, double-blind, randomised trial that is part of a
larger clinical programme focused on capivasertib, an investigational AKT
(serine/threonine kinase) inhibitor. CAPItello-291 is evaluating the efficacy
of capivasertib in combination with Faslodex versus placebo plus Faslodex for
the treatment of locally advanced (inoperable) or metastatic HR-positive,
HER2-low or 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 subgroup of patients whose tumours have qualifying alterations in the
PIK3CA, AKT1 or PTEN genes. In the trial, approximately 40% of tumours had
PI3K/AKT/PTEN alterations.

 

Capivasertib

Capivasertib is an investigational oral treatment currently in Phase III
trials for the treatment of multiple subtypes of breast cancer, prostate
cancer and a Phase II trial for haematologic malignancies. A potent, selective
adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms
(AKT1/2/3), capivasertib is being evaluated in combination with existing
therapies in tumours harbouring alterations in the PI3K/AKT/PTEN pathway, and
in tumours reliant on signalling via this pathway for survival. Capivasertib
is dosed according to an intermittent schedule, which consists of four days on
and three days off. This was chosen in early phase trials based on
tolerability and the degree of target inhibition.

 

The capivasertib clinical research programme is investigating the safety and
efficacy of capivasertib when used in combination with established treatment
regimens.

 

Capivasertib 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 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 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 (fulvestrant) and Zoladex (goserelin) and
aims to reshape the HR-positive space with ngSERD and potential new medicine
camizestrant as well as a potential first-in-class AKT kinase inhibitor,
capivasertib. 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 metastatic breast cancer patients
with an inherited BRCA mutation and are exploring new opportunities to treat
these patients earlier in their disease.

 

To bring much-needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is testing
immunotherapy Imfinzi (durvalumab) in combination with other oncology
medicines, including Lynparza and Enhertu, evaluating the potential of
capivasertib in combination with chemotherapy, and datopotamab deruxtecan.

 

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 (http://www.astrazeneca.com/)  and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts
For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1. 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.

2. National Cancer Institute. Surveillance, Epidemiology and End Results
Program. Available at
https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(https://seer.cancer.gov/statfacts/html/breast-subtypes.html) Accessed October
2022.

3. 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.

4.(   ) Bae SY, et al. Poor prognosis of single hormone receptor- positive
breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer.
2015; 10.1186/s12885-015-1121-4.

5.  Lumachi F, et al. Current medical treatment of estrogen receptor-positive
breast cancer. World J Biol Chem. 2015; 10.4331/wjbc.v6.i3.231.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCEQLBLLBLEFBL