Phase 3 Study of Capivasertib Plus Chemo/ADT in mCRPC to End After Recommendation From Data Monitoring Committee

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Credit: © Sebastian Kaulitzki
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The phase 3 CAPItello-280 trial (NCT05348577) evaluating capivasertib (Truqap) plus docetaxel and androgen deprivation therapy (ADT) vs placebo plus docetaxel and ADT for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) is being discontinued following a recommendation from the study’s independent data monitoring committee.1

The committee’s recommendation followed a review of data from a prespecified interim analysis for the study. Data demonstrated that the capivasertib combination was unlikely to meet the trial’s dual primary end points of radiographic progression-free survival (rPFS) and overall survival (OS).

Safety data for capivasertib were consistent with findings from previous clinical trials.

CAPItello-280 was a randomized, double-blind, placebo-controlled trial that enrolled patients at least 18 years of age with histologically confirmed prostate adenocarcinoma without predominant neuroendocrine or small cell cancers.2 Patients needed to have metastatic disease with at least 1 bone lesion and/or 1 soft tissue lesion, and they also were required to have mCRPC with progression despite receiving ADT. Prior treatment with a next-generation hormonal agent for at least 3 months and evidence of disease progression were also needed.

Other key inclusion criteria comprised an ECOG or WHO performance status of 0 or 1; a life expectancy of at least 12 weeks; a serum testosterone level of no more than 50 ng/dL; and ongoing treatment with ADT with an LHRH agonist, LHRH antagonist, or bilateral orchiectomy.

Investigators excluded patients with brain metastases or symptomatic spinal cord compression; a mean resting QTc of more than 470 msec over 3 consecutive electrocardiograms; clinically significant abnormalities of glucose metabolism; and inadequate bone marrow reserve or organ function.

Patients were randomly assigned to receive capivasertib at 320 mg twice per day on days 2 to 5, 9 to 12, and 16 to 19 of each 21-day cycle or placebo on the same schedule. Treatment with capivasertib or placebo continued until disease progression, unacceptable toxicity, or patient withdrawal. In both arms, patients received docetaxel at 75 mg/m2 once every 3 weeks for 6 to 10 cycles, along with ADT.

Beyond the dual primary end points of rPFS and OS, secondary end points included rPFS and OS in patients with PTEN-deficient and -proficient tumors; time to pain progression; time to first symptomatic skeletal event; time to deterioration of urinary symptoms; time to deterioration of physical functioning; and overall pain severity.

In November 2023, the FDA approved capivasertib in combination with fulvestrant (Faslodex) for the treatment of adult patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations, as detected by an FDA-approved test, following progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.3

Capivasertib is not approved by the FDA in any prostate cancer indications. Ongoing studies are further investigating the agent in other populations of patients with breast cancer and prostate cancer, including the phase 3 CAPItello-281 trial (NCT04493853).1 The study met its primary end point of improved rPFS with capivasertib plus abiraterone acetate (Zytiga) and ADT vs placebo plus abiraterone and ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer.4

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 teatment for metastatic castration resistant prostate cancer (mCRPC) (CAPItello280). ClinicalTrials.gov. Updated January 27, 2025. Accessed May 1, 2025. https://clinicaltrials.gov/study/NCT05348577
3. FDA approves capivasertib with fulvestrant for breast cancer. FDA. 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