AstraZeneca has announced positive high-level results of Truqap (capivasertib) from the CAPItello-281 Phase 3 trial in PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC) patients.
Truqap was evaluated in combination with abiraterone and androgen deprivation therapy (ADT).
Capivasertib is an ATP-competitive inhibitor targeting all three AKT isoforms (AKT1/2/3). It was discovered by AstraZeneca through a collaboration with Astex Therapeutics.
The CAPItello-281 study is a double-blind, randomised trial. It assessed the efficacy and safety of Truqap combined with abiraterone and ADT versus abiraterone, ADT, and placebo.
The global trial enrolled 1,012 adult patients with confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency.
The primary endpoint of the trial is radiographic progression-free survival (rPFS), with overall survival (OS) as a secondary endpoint.
According to the results, the combination of Truqap, abiraterone, and ADT significantly improved rPFS in patients with PTEN-deficient de novo mHSPC.
This outcome is clinically meaningful when compared to abiraterone and ADT with placebo.
OS data were not fully mature at the time of analysis. However, the capivasertib combination showed an early trend toward improved OS compared to abiraterone and ADT with placebo.
The trial will continue as planned to further evaluate OS.
The safety profile of Truqap, combined with abiraterone and ADT in CAPItello-281, was consistent with the known profiles of each individual therapy.
AstraZeneca said that data from the trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.
AstraZeneca oncology research and development (R&D) executive vice president Susan Galbraith 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.”
The ATP-competitive inhibitor is already approved in the US, EU, Japan, and other countries to treat adult patients with HR-positive (or ER-positive) and HER2-negative locally advanced or metastatic breast cancer with biomarker alterations, following recurrence or progression after endocrine therapy. It is also approved in Australia for similar indications.
In July 2024, AstraZeneca secured the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) approval for Truqap to treat advanced breast cancer.
Truqap is currently being evaluated in the Phase 3 CAPItello-292 trial for breast cancer and in the CAPItello-280 and CAPItello-281 trials for prostate cancer.
