Investigators Discontinue Trial Assessing Capivasertib in Metastatic CRPC

The safety profile of capivasertib in the phase 3 CAPItello-280 trial (NCT05348577) was comparable with prior reports of the agent.

Developer AstraZeneca has announced the discontinuation of the phase 3 CAPItello-280 trial (NCT05348577) evaluating capivasertib (Truqap) plus docetaxel and androgen deprivation therapy (ADT) among patients with metastatic castration-resistant prostate cancer (CRPC), according to a press release from the developer.¹

The trial’s discontinuation followed a recommendation from an independent data monitoring committee. Based on an evaluation of data from a prespecified interim analysis, the committee determined that capivasertib plus docetaxel/ADT was unlikely to reach the trial’s primary end points of radiographic progression-free survival (rPFS) and overall survival (OS) vs placebo plus docetaxel/ADT. The safety profile of capivasertib in CAPItello-280 was comparable with prior reports of the agent.

Developers will collaborate with trial investigators to facilitate follow-up assessments with patients.

Investigators of the double-blind, randomized phase 3 CAPItello-280 trial previously highlighted the study’s design as part of a trials in progress poster session at the 2023 ASCO Genitourinary Cancers Symposium.²

According to the study investigators, docetaxel was the standard frontline chemotherapy option for those with metastatic CRPC, which included patients who experienced progression on androgen receptor–targeted (ARTA) agents. They noted, however, that most patients may develop resistance to chemotherapy and that the median OS across this population was under 3 years in clinical trials. Based on this background, investigators described a need to improve survival in metastatic CRPC while exploring docetaxel-based combinations as a new approach to treatment.

Furthermore, investigators highlighted prior findings from the phase 2 ProCAID trial (NCT02121639) evaluating capivasertib/docetaxel vs placebo/docetaxel among 150 patients with metastatic CRPC. Data from the ProCAID trial showed that composite PFS outcomes were similar between the treatment groups, although capivasertib-based treatment extended OS; follow-up analysis indicated a sustained OS benefit in patients who received prior ARTA therapy.

Given this context, investigators conducted the phase 3 CAPItello-280 trial to validate the results from the ProCAID trial while using the same capivasertib dose and schedule. A total of 1033 adult patients with histologically confirmed prostate adenocarcinoma and evidence of metastatic CRPC were randomly assigned 1:1 to receive 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’s primary end points were rPFS per investigator assessment and OS across the overall trial population. Secondary end points included time to pain progression, symptomatic skeletal-related events, safety and tolerability, patient-reported outcomes, and pharmacokinetic outcomes.

Patients 18 years or older with metastatic CRPC and no prior chemotherapy were eligible for enrollment on the trial. Other eligibility criteria included having ARTA therapy for hormone-sensitive prostate cancer or CRPC for at least 3 months and evidence of disease progression, a serum testosterone level of no more than 50 ng/dL, eligibility to receive docetaxel, receipt of ongoing AFT, and an ECOG performance status of 0 or 1.

Those with radiotherapy to at least 30% of bone marrow within 4 weeks beginning study treatment or major surgery within 4 weeks of initiating treatment were ineligible for study entry. Patients were also excluded from the trial if they had brain metastases or spinal cord compression, cardiac abnormalities, clinically significant glucose metabolism abnormalities, inadequate bone marrow reserve or organ function, or specified prior or concomitant therapy. Having history of another primary malignancy apart from disease treated with curative intent with no known active disease within the past 5 years and of a low potential risk recurrence was also grounds for exclusion.

References

1. Update on CAPItello-280 phase III trial of Truqap in metastatic castration-resistant prostate cancer. News release. AstraZeneca. April 29, 2025. Accessed April 29, 2025. https://tinyurl.com/bddbksct
2. Crabb SJ, Ye D-W, Uemura H, et al. CAPItello-280: a phase III study of capivasertib and docetaxel versus placebo and docetaxel in metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(suppl 6):TPS287. doi:10.1200/JCO.2023.41.6_suppl.TPS287