AstraZeneca discontinues Phase 3 trial of Truqap in metastatic castration-resistant prostate cancer
Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics.
AstraZeneca has announced the discontinuation of the CAPItello-280 Phase III trial evaluating the efficacy and safety of Truqap (capivasertib) in combination with docetaxel and androgen-deprivation therapy (ADT) compared to docetaxel and ADT with placebo in patients with metastatic castration-resistant prostate cancer (mCRPC).
This decision is based on the recommendation of the Independent Data Monitoring Committee (IDMC) following their review of data from a pre-specified interim analysis, which concluded that the Truqap combination was unlikely to meet the dual primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) versus the comparator arm upon trial completion. The safety profile for Truqap was consistent with previous trials.
"The Company will work with investigators to ensure the necessary follow up with patients. Data from the trial will inform ongoing research," AstraZeneca stated in a release.
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 over 397,000 deaths in 2022.
Metastatic prostate cancer is associated with a significant mortality rate, with only one third of patients surviving five years after diagnosis. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.
CAPItello-280 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of Truqap in combination with docetaxel and ADT compared to docetaxel and ADT in combination with placebo in patients with mCRPC.
The global trial enrolled 1,033 adult patients with histologically confirmed prostate adenocarcinoma with evidence of mCRPC with progression of disease despite ADT. The dual primary endpoints of the CAPItello-280 trial are rPFS as assessed by investigator and OS in the overall trial population. Key secondary endpoints include OS and rPFS as assessed by investigator in patients with mCRPC and PTEN-deficient tumours, OS and rPFS as assessed by investigator in patients with mCRPC and PTEN-proficient tumours, time to pain progression (TTPP) in the overall trial population and time to first symptomatic skeletal-related event (SSRE) in the overall trial population.
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 several 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 being evaluated in ongoing Phase III trials for the treatment of breast and prostate cancers.
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).
