CAPItello-280 Phase III Trial Update: Truqap in Metastatic Castration-Resistant Prostate Cancer

AstraZeneca has announced the discontinuation of the CAPItello-280 Phase III trial, which was assessing the effectiveness and safety of Truqap (capivasertib) when combined with docetaxel and androgen-deprivation therapy (ADT) in comparison to a placebo with docetaxel and ADT in patients suffering from metastatic castration-resistant prostate cancer (mCRPC). This decision followed the recommendation from the Independent Data Monitoring Committee (IDMC) after a pre-specified interim analysis suggested that the Truqap combination was unlikely to achieve its dual primary objectives of improving radiographic progression-free survival (rPFS) and overall survival (OS) against the comparator arm upon the trial's conclusion. The safety profile of Truqap remained consistent with previous investigations. AstraZeneca plans to collaborate with trial investigators to ensure follow-up with patients, and the data gathered will support ongoing research efforts.

Prostate cancer stands as the second most common cancer among men and is the fifth leading cause of male cancer death worldwide. In 2022, the incidence exceeded 1.4 million cases with over 397,000 deaths. Metastatic prostate cancer is associated with a high mortality rate, with only about one-third of patients surviving beyond five years post-diagnosis. The disease's progression is often fueled by male sex hormones, including testosterone.

Within five years, approximately 10-20% of men with advanced prostate cancer may develop castration-resistant prostate cancer, where the cancer continues to grow and spread despite androgen-deprivation therapy aimed at blocking male sex hormones. At the point of diagnosis with castration-resistant prostate cancer, at least 84% of these individuals will have metastases, and among those without metastases at diagnosis, about 33% may develop metastases within two years. Although there have been advancements in treatments for mCRPC with taxanes and novel hormonal agents, a significant unmet medical need remains for this patient population.

The CAPItello-280 trial was a global, double-blind, randomized study involving 1,033 adult participants with histologically confirmed prostate adenocarcinoma and mCRPC, whose disease advanced despite ADT. It focused on dual primary endpoints: rPFS and OS in the overall trial population. Secondary endpoints included OS and rPFS in mCRPC patients with PTEN-deficient and PTEN-proficient tumors, time to pain progression, and time to the first symptomatic skeletal-related event.

Truqap, a first-in-class ATP-competitive inhibitor targeting all three AKT isoforms, is administered at a dosage of 400mg twice daily on a schedule of four days on, three days off. This regimen was chosen during early trials based on tolerability and target inhibition levels. Truqap, in combination with Faslodex (fulvestrant), has received approval in several countries, including the US, EU, Japan, and China, for treating HR-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations. This approval is supported by results from the CAPItello-291 trial. Further evaluations of Truqap are underway in Phase III trials targeting both breast and prostate cancers.

AstraZeneca, a leader in oncology, continues to strive for breakthroughs in cancer treatment with the aim of eradicating cancer as a cause of death. Based in Cambridge, UK, AstraZeneca is a global biopharmaceutical company engaged in the discovery, development, and commercialization of prescription medicines across various fields, including oncology. Its innovative medicines are available in over 125 countries, impacting millions of patients worldwide.