AstraZeneca has announced the discontinuation of its Phase 3 CAPItello-280 trial evaluating Truqap (capivasertib) in combination with docetaxel and androgen deprivation therapy (ADT) for patients with metastatic castration-resistant prostate cancer (mCRPC).
The decision follows a recommendation from the Independent Data Monitoring Committee (IDMC) after their review of a pre-specified interim analysis. The committee concluded that the Truqap combination was unlikely to meet the trial's dual primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus docetaxel and ADT.
According to AstraZeneca, the safety profile observed for Truqap in the CAPItello-280 trial was consistent with previous studies of the agent. The company stated it will work with investigators to ensure appropriate follow-up with the 1,033 patients enrolled in the global trial.
Trial Design and Background
The CAPItello-280 study was a double-blind, randomized Phase 3 trial that enrolled adult patients with histologically confirmed prostate adenocarcinoma and evidence of mCRPC. Participants were randomly assigned 1:1 to receive either capivasertib or matched placebo at 320 mg orally twice daily for 4 days on and 3 days off, plus docetaxel at 75 mg/m² intravenously on day 1 of each 21-day cycle for 6 to 10 cycles.
The trial was designed to validate results from the earlier Phase 2 ProCAID trial (NCT02121639), which had shown extended overall survival with capivasertib-based treatment, particularly in patients who had received prior androgen receptor-targeted (ARTA) therapy.
Dr. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, commented: "While we are disappointed by these results, the data from this trial will provide valuable insights to inform our ongoing research in prostate cancer treatments."
Unmet Need in Metastatic CRPC
Prostate cancer remains the second most prevalent cancer in men globally, with more than 1.4 million new cases and over 397,000 deaths reported in 2022. Metastatic prostate cancer is associated with poor outcomes, with only one-third of patients surviving five years after diagnosis.
Approximately 10-20% of men with advanced prostate cancer develop castration-resistant disease within five years. At least 84% of these patients have metastases at the time of CRPC diagnosis, and of those without metastases at diagnosis, 33% are likely to develop them within two years.
Docetaxel has been the standard frontline chemotherapy option for patients with mCRPC, including those who experience progression on ARTA agents. However, most patients develop resistance to chemotherapy, with median overall survival under three years in clinical trials, highlighting the significant unmet need for improved treatment options.
About Truqap (Capivasertib)
Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). It is administered at 400mg twice daily on an intermittent dosing schedule of four days on and three days off.
Despite this setback in prostate cancer, 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 hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations (PIK3CA, AKT1, or PTEN) following progression on endocrine-based regimens.
AstraZeneca continues to evaluate Truqap in other ongoing Phase 3 trials for breast and prostate cancers as part of its broader oncology portfolio.
Future Directions
While the CAPItello-280 trial did not meet its expected endpoints, AstraZeneca has indicated that data from the study will inform ongoing research efforts. The company maintains its commitment to addressing the significant unmet needs in prostate cancer treatment through continued investigation of novel therapeutic approaches.
For patients with mCRPC, the search for effective treatment combinations beyond current standards of care remains a critical area of clinical research, particularly for those who have progressed on existing therapies and have limited options.
