1423TiP CYCLONE 3: A phase III, randomized, double-blind, placebo-controlled study of abemaciclib in combination with abiraterone plus prednisone in men with high-risk metastatic hormone-sensitive prostate cancer (mHSPC)

Landmark trials led to the integration of docetaxel (D) or novel hormonal agents (NHA) added androgen deprivation therapy (ADT) into treatment paradigm for mHSPC. Recent data showed survival benefit intensification with ADT+D+NHA triplet vs ADT+D in selected patients (pts). Yet, there is a significant medical need expand therapeutic options especially pts poor prognoses, including those not candidates chemotherapy. Abemaciclib an oral selective inhibitor cyclin-dependent kinase 4 and 6 (CDK4 & 6) dosed on continuous schedule, approved advanced metastatic certain types high-risk early stage HR+, HER2- breast cancer. Analogous estrogen receptor signaling pathway cancer, evidence that axis activates CDK4 sustain prostate cancer cell proliferation, upregulation cyclin D1 potential mechanism resistance NHA therapy. In preclinical models, abemaciclib induces cycle arrest tumor growth inhibition. CYCLONE 3 global, randomized, double-blind, placebo-controlled study evaluating addition abiraterone+prednisone (AP) Approximately 900 mHSPC defined by ≥4 bone metastasis and/or visceral disease will be randomised 1:1 ratio AP + placebo arm. Up months prior ADT alone, up cycles D+ADT, permitted absence radiographic PSA progression. Pts who have undergone orchiectomy continue ADT. Stratification factors are de novo mHSPC, metastases use. Primary endpoint investigator-assessed progression-free (rPFS). Key secondary endpoints include rPFS assessed blinded independent central review, castration-resistant cancer-free survival, overall time pain progression, safety pharmacokinetics. Enrollment open at approximately 270 sites across 25 countries. NCT05288166. Scientific writing support was provided Garreth Lawrence, employee Eli Lilly Company.