REG - AstraZeneca PLC - Update on CAPItello-290 Phase III trial

AstraZenecaAnnouncement

18/06/2024 07:00

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RNS Number : 8458S  AstraZeneca PLC  18 June 2024

18 June 2024

 

Update on the CAPItello-290 Phase III trial for Truqap plus chemotherapy

in advanced or metastatic triple-negative breast cancer

 

The CAPItello-290 Phase III trial for Truqap (capivasertib) in combination
with paclitaxel in patients with locally advanced (inoperable) or metastatic
triple-negative breast cancer (TNBC) did not meet the dual primary endpoints
of improvement in overall survival (OS) versus paclitaxel in combination with
placebo in either the overall trial population or in a subgroup of patients
with tumours harbouring specific biomarker alterations (PIK3CA, AKT1 or PTEN).

 

Breast cancer is the second most common cancer and one of the leading causes
of cancer-related deaths worldwide.(1) While some breast cancers may test
positive for estrogen receptors, progesterone receptors or overexpression of
human epidermal growth factor receptor 2 (HER2), TNBC is defined as negative
for all three.(2) In the 1st-line setting, approximately 59,000 patients with
TNBC are treated with a medicine.(3) Collectively, mutations in PIK3CA, AKT1
and alterations in PTEN affect approximately 35% of patients with TNBC.(4)

 

Peter Schmid, MD, Barts Cancer Institute, London, UK, and principal
investigator for the trial said: "Despite modest advances, triple-negative
breast cancer remains one of the most challenging forms of disease to treat
due to the lack of known actionable biomarker targets, and chemotherapy-based
regimens continue to be the mainstay of treatment. While the CAPItello-290
trial results have not shown what we hoped, they provide important information
to further understand this aggressive form of breast cancer where patients are
in urgent need of new treatments."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "We are committed to advancing science for patients in some of the most
challenging cancers, including this heterogeneous subtype of breast cancer.
While we are disappointed in the CAPItello-290 outcome, these results will
further our understanding of the role of the PI3K/AKT pathway in breast cancer
as we continue our clinical research across the Truqap clinical development
programme and across our pipeline."

 

The safety profile of Truqap in combination with paclitaxel in CAPItello-290
was broadly consistent with the known safety profile of each medicine with no
new safety concerns identified. Data will be shared in due course.

 

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.

 

Notes

 

Triple-negative breast cancer

1st-line treatment for advanced or metastatic TNBC usually consists of
chemotherapy alone or in combination with an immunotherapy - options generally
associated with response rates between 30 to 50%.(2,5,6) Among patients with
tumours that do respond to initial treatment, disease progression is common
and rapid, often occurring within two years.(2,6-8) The average overall
survival of patients living with advanced or metastatic TNBC is 12 to 18
months, with only about 14% of patients living five years following
diagnosis.(9,10)

 

CAPItello-290

CAPItello-290 is a Phase III, double-blind, randomised trial evaluating the
efficacy and safety of Truqap in combination with paclitaxel versus placebo
in combination with paclitaxel in the 1st-line treatment of patients with
locally advanced (inoperable) or metastatic TNBC.

 

The global trial enrolled 923 adult patients with histologically confirmed
locally advanced or metastatic TNBC. The trial has dual primary endpoints of
OS 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).

 

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, Japan 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 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 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), 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 (http://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/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.   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.   O'Reilly D, et al. Overview of recent advances in metastatic triple
negative breast cancer. World J Clin Oncol. 2021; 12(3):164-182.

3.   Cerner CancerMPact database. Accessed May 2024.

4.   Cocco S, et al. Biomarkers in Triple-Negative Breast Cancer:
State-of-the-Art and Future Perspectives. Int J Mol Sci. 2020; 21(13): 4579.

5.   Bergin A, et al. Triple-negative breast cancer: recent treatment
advances. F1000Res. 2019; 8:10.12688/f1000research.18888.1.

6.   Zhang Y, et al. Genomic features of rapid versus late relapse in triple
negative breast cancer. BMC Cancer. 2021; 21(568).

7.   Cortes J, et al. Pembrolizumab plus Chemotherapy in Advanced Triple
-Negative Breast

Cancer. N Engl J Med. 2022; 387:217-226. 10.1056/NEJMoa2202809.

8.   Emans L, et al. Atezolizumab and nab-Paclitaxel in Advanced
Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study.
J Natl Cancer Inst. 2021; 113(8): Djab004.

9.   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 June
2024.

10.  Sharma P, et al. Biology and Management of Patients with Triple-Negative
Breast Cancer. Oncologist. 2016; 21(9);1050-62.
10.1634/theoncologist.2016-0067.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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