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Phase 3 trial of capivasertib in mCRPC discontinued following IDMC recommendation
Key Takeaways
- The CAPItello-280 trial was terminated due to unlikely achievement of primary endpoints in metastatic castration-resistant prostate cancer.
- Capivasertib, an ATP-competitive AKT inhibitor, showed a consistent safety profile but is not approved for prostate cancer.
The committee determined that the study was unlikely to meet its dual primary end points of radiographic progression-free survival and overall survival.
The phase 3 CAPItello-280 trial (NCT05348577) has been discontinued following a recommendation from the Independent Data Monitoring Committee (IDMC), AstraZeneca announced in a news release.1
The safety profile for capivasertib was consistent with previous data.
The study was assessing the safety and efficacy of adding capivasertib (Truqap) to docetaxel and androgen deprivation therapy (ADT) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The IDMC recommendation was issued following a pre-specified interim analysis of the data, in which the committee determined that the study was unlikely to meet its dual primary end points of radiographic progression-free survival (rPFS) and overall survival (OS).
The safety profile for capivasertib was consistent with previously reported data, the company noted.
In total, the double-blind study enrolled 1,033 adult patients with mCRPC whose tumors had progressed on prior ADT. Patients in the study were randomly assigned 1:1 to receive capivasertib plus docetaxel and ADT or to placebo plus docetaxel and ADT.2
In addition to the dual primary end points of rPFS and OS, key secondary end points included time to pain progression and the time to first symptomatic skeletal-related event. The trial was also assessing rPFS and OS in patients stratified by PTEN status.
According to AstraZeneca, “The company will work with investigators to ensure the necessary follow up with patients. Data from the trial will inform ongoing research.”
Additional information on capivasertib
Capivasertib is a “first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all 3 AKT isoforms (AKT1/2/3),” according to the company.
The therapy is currently approved in combination with fulvestrant (Faslodex) in the US, as well as several other countries, for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with 1 or more biomarker alterations (PIK3CA, AKT1, or PTEN) following recurrence or progression on or after an endocrine-based regimen. This approval was granted based on results from the CAPItello-291 trial (NCT04305496), in which the combination extended PFS vs placebo plus fulvestrant.3
Capivasertib is not approved for any indication in prostate cancer.
In November 2024, AstraZeneca reported positive high-level results of the phase 3 CAPItello-281 trial (NCT04493853), assessing capivasertib in combination with abiraterone and ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer.4 Overall, the trial met its primary end point, showing that capivasertib plus abiraterone and ADT led to a statistically significant and clinically meaningful improvement in rPFS vs placebo plus abiraterone and ADT.
Although the OS data were immature at the time of data report, AstraZeneca noted a trend favoring the capivasertib arm. The study remains ongoing, with final completion expected in March 2027.5
REFERENCES
1. Update on CAPItello-280 Phase III trial of Truqap in metastatic castration-resistant prostate cancer. News release. AstraZeneca. April 29, 2025. Accessed May 1, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/update-on-capitello-280-phase-iii-trial.html
2. Study of capivasertib + docetaxel vs placebo + docetaxel as treatment for metastatic castration resistant prostate cancer (mCRPC) (CAPItello280). ClinicalTrials.gov. Last updated January 27, 2025. Accessed May 1, 2025. https://clinicaltrials.gov/study/NCT05348577
3. FDA approves capivasertib with fulvestrant for breast cancer. News release. US Food & Drug Administration. November 16, 2023. Accessed May 1, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer
4. Truqap combination in PTEN-deficient metastatic hormone-sensitive prostate cancer demonstrated statistically significant and clinically meaningful improvement in radiographic progression-free survival in CAPItello-281 Phase III trial. News release. AstraZeneca. November 25, 2024. Accessed May 1, 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/truqap-improved-rpfs-in-advanced-prostate-cancer.html
5. Capivasertib+abiraterone as treatment for patients with metastatic hormone-sensitive prostate cancer and PTEN deficiency (CAPItello-281). ClinicalTrials.gov. Last updated April 10, 2025. Accessed May 1, 2025. https://clinicaltrials.gov/study/NCT04493853
