KEY TAKEAWAYS
- CYCLONE 3 (NCT05288166) is a global, randomized, double-blind, placebo-controlled study evaluating the addition of abemaciclib to abiraterone+prednisone (AP) in patients with high-risk mHSPC.
- Abemaciclib is an oral selective inhibitor of cyclin-dependent kinase 4 and 6 (CDK4 & 6) approved for treating node-positive high-risk early-stage and advanced or metastatic HR+, HER2- breast cancer.
- The primary endpoint of CYCLONE 3 is investigator-assessed rPFS. Key secondary endpoints include rPFS assessed by blinded independent central review, castration-resistant prostate cancer-free survival, overall survival, time to pain progression, safety, and pharmacokinetics.
- Enrollment is open at approximately 270 sites across 25 countries, and up to 900 patients with high-risk mHSPC defined by ≥4 bone metastasis and/or visceral disease will be randomized in a 1:1 ratio to the AP + abemaciclib or AP + placebo arm.
Adding new hormonal drugs (NHA) to androgen deprivation therapy (ADT) for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) has improved survival in landmark trials. However, since the prognosis for patients with high-risk mHSPC is poor, there is a pressing need to increase therapy choices. To treat node-positive, high-risk, early-stage, and advanced or metastatic HR+, HER2-breast cancer, abemaciclib, an oral, selective inhibitor of cyclin-dependent kinase 4 and 6 (CDK4 & 6), is approved.
The increase of cyclin D1 is a potential mechanism of resistance to NHA therapy in prostate cancer, and the androgen receptor axis has been shown to stimulate CDK4 and 6 to maintain prostate cancer cell proliferation, similar to the estrogen receptor signaling pathway in breast cancer. Abemaciclib promotes cell cycle arrest and suppresses prostate tumor development in preclinical animals. Patients with high-risk mHSPC will be eligible to participate in CYCLONE 3 (NCT05288166), a worldwide, randomized, double-blind, placebo-controlled research evaluating the addition of abemaciclib to abiraterone+prednisone (AP). Over 900 patients with high-risk mHSPC (defined as 4 bone metastases and/or visceral illness) will be randomly assigned to either the AP + abemaciclib or AP + placebo arm.
Prior treatment for mHSPC will be excluded per planned protocol revision, although up to 3 months of ADT are allowed before randomization. Patients (Pts) without an orchiectomy will keep receiving ADT. De novo mHSPC and visceral metastases are used as stratification variables. Investigator-assessed radiographic progression-free survival is the primary outcome (rPFS). Castration-resistant prostate cancer-free survival, overall survival, time to pain progression, safety, and pharmacokinetics will all be important secondary outcomes. Over 270 locations in 25 countries are now accepting participants.
Source: https://meetings.asco.org/abstracts-presentations/217258
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT05288166/
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