REG - AstraZeneca PLC - FDA ODAC recommends Truqap in prostate cancer

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RNS Number : 6965C  AstraZeneca PLC  01 May 2026

01 May 2026

Truqap recommended by FDA Advisory Committee for PTEN-deficient metastatic
hormone-sensitive prostate cancer

ODAC overwhelming majority voted that Truqap plus abiraterone and ADT
demonstrated a favourable benefit risk profile for patients based on the
CAPItello-281 Phase III trial results

First and only targeted treatment combination to demonstrate benefit in this
subtype of prostate cancer addresses significant unmet patient need

The US Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee
(ODAC) has recognised a favourable benefit risk profile for AstraZeneca's
Truqap (capivasertib) in combination with abiraterone and androgen deprivation
therapy (ADT) for the treatment of patients with PTEN-deficient metastatic
hormone-sensitive prostate cancer (mHSPC), based on the CAPItello-281 Phase
III trial. The Committee voted 7 to 1, with 1 abstaining.

 

In August 2025, the FDA accepted the supplemental New Drug Application (sNDA)
for Truqap in combination with abiraterone and ADT based on positive results
from the CAPItello-281 Phase III trial, presented at the 2025 European Society
for Medical Oncology (ESMO) Congress and simultaneously published in Annals of
Oncology (https://www.annalsofoncology.org/) .(1)

 

Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute
and investigator for the trial, said: "Patients identified to have
PTEN-deficient metastatic hormone-sensitive prostate cancer have an aggressive
form of the disease and currently experience poor outcomes. Their disease
significantly impacts their quality of life and inevitably progresses to more
advanced stages that are associated with high mortality rates. In addition to
this poor prognosis, patients currently have limited treatment options, which
is why today's recommendation of the capivasertib combination is welcome news
for both patients and clinicians to address an urgent need for new treatments
that delay progression."

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "CAPItello-281 is the first pivotal trial to prospectively
define PTEN-deficient metastatic hormone-sensitive prostate cancer and its
severe course of disease. The Committee's recognition of the unmet need in
patients with PTEN-deficiency and of the benefit seen with the Truqap
combination verifies its potential to address this significant need and
optimise outcomes for patients. We are committed to working closely with the
FDA to bring the first and only targeted treatment option to the one in four
patients with this form of metastatic hormone-sensitive prostate cancer."

 

Results from the primary analysis of the CAPItello-281 Phase III trial showed
a statistically significant 19% reduction in the risk of radiographic disease
progression or death and a clinically meaningful improvement in median
radiographic progression-free survival (rPFS) of 7.5 months with the Truqap
combination versus treatment with abiraterone and ADT with placebo (based on a
hazard ratio  HR  of 0.81; 95% confidence interval  CI  0.66-0.98; p=0.034).
Median rPFS was 33.2 months for the Truqap combination versus 25.7 months for
the comparator arm.(1)

 

A consistent benefit was observed with the Truqap combination versus treatment
with abiraterone and ADT with placebo in key secondary endpoints of the trial,
including prolonged time to castration resistance (29.5 vs. 22.0 months [HR
0.77; 95% CI: 0.63-0.94]) and prostate-specific antigen (PSA) progression (HR
0.73; 95% CI: 0.52-1.01), and fewer and delayed events in terms of symptomatic
skeletal event-free survival (SSE-FS) (42.5 vs. 37.3 months [HR 0.82, 95% CI:
0.66-1.02]).(1)

 

Overall survival (OS) data were immature at the time of primary analysis;
however, subsequent interim results for OS numerically favoured the Truqap
combination versus the comparator arm. The trial will continue as planned to
further assess OS as a key secondary endpoint.

 

The safety profile of Truqap in combination with abiraterone and ADT in
CAPItello-281 was broadly consistent with the known profile of each medicine.
Consistent with the addition of a targeted treatment to background therapy,
Grade 3 or higher adverse events occurred in 67% of patients treated with the
Truqap combination versus 40.4% of patients treated with abiraterone and ADT
with placebo. The most common Grade 3 or higher adverse events in the Truqap
arm were rash (12.3%), hyperglycaemia (10.3%), hypokalaemia (8.7%), diarrhoea
(6.2%), hypertension (5.8%) and anaemia (5.2%).(1)

 

The ODAC provides the FDA with independent, expert advice and recommendations
on marketed and investigational medicines for use in the treatment of cancer.
The FDA will consider the feedback as it reviews the submission and is not
bound by the Committee's recommendation.

 

A regulatory application for Truqap in combination with abiraterone and ADT
for the treatment of PTEN-deficient mHSPC is under review in the EU based on
the CAPItello-281 Phase III trial.

 

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.(2) In the US, prostate
cancer is the most common cancer in men, with more than 300,000 new cases of
the disease diagnosed annually, and more than 36,000 deaths.(3)

 

Metastatic prostate cancer is associated with a significant mortality rate,
with only one third of patients surviving five years after diagnosis.(4)
Development of prostate cancer is often driven by male sex hormones called
androgens, including testosterone.(5)

 

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.(5,6) 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.(6,7) 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.(6-8)

 

Newly diagnosed mHSPC is an aggressive form of the disease associated with
poor outcomes and survival.(6,8) Globally, approximately 200,000 patients are
diagnosed with mHSPC each year, with 35,000 patients diagnosed with the
disease in the US.(9) One in four of these patients have PTEN-deficient
tumours.(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.(10,11)

 

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 in combination with Faslodex (fulvestrant) is approved in the US, EU,
Japan, China and a number of other countries for the treatment of adult
patients with HR-positive (or estrogen receptor-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-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 (https://www.astrazeneca.com/)

AstraZeneca (LSE/STO/NYSE: 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 (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
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.

 

References

1.   Fizazi K, et al. Capivasertib plus abiraterone in PTEN-deficient
metastatic hormone sensitive prostate cancer: CAPItello-281 phase III study.
Ann Oncol 2026; 37(1):53-68.

2.   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.

3.   American Cancer Society. Key Statistics for Prostate cancer. Available
at:
https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
(https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html)
. Accessed April 2026.

4.   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.

5.   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 April 2026.

6.   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 April 2026.

7.   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 April 2026.

8.   Hussain M, et al. Metastatic Hormone-Sensitive Prostate Cancer and
Combination Treatment Outcomes A Review. JAMA Oncol. 2024;10(6):807-820.

9.   Cerner CancerMPact database. Accessed April 2026.

10.  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.

11.  Gasmi A, et al. Overview of the Development and Use of Akt Inhibitors in
Prostate Cancer. J Clin Med. 2021;11(1):160.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

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