Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial

Abstract

Orion Corporation Orion Pharma, Endo Pharmaceuticals Inc.

Erratum to: Phase 1 study of darolutamide (ODM-201), a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer

“…Darolutamide administered as a single 300-or 600-mg once-daily dose (with and without food) or as multiple doses of 300 mg BID or 600 mg BID for a median treatment duration of 84 days (range 31-328) was well tolerated in this heavily treated population, and overall toxicities were consistent with the known safety profile of darolutamide in a previously reported phase 1 trial in a Western study population [13,17]. Our results show that there are no remarkable differences in PK parameters between Japanese and Western patients with mCRPC [13,17].…”

“…Darolutamide administered as a single 300-or 600-mg once-daily dose (with and without food) or as multiple doses of 300 mg BID or 600 mg BID for a median treatment duration of 84 days (range 31-328) was well tolerated in this heavily treated population, and overall toxicities were consistent with the known safety profile of darolutamide in a previously reported phase 1 trial in a Western study population [13,17]. Our results show that there are no remarkable differences in PK parameters between Japanese and Western patients with mCRPC [13,17]. For example, Western patients in the ARAFOR study who were administered a single dose of darolutamide 600 mg had C max and AUC 0-48 values approximately twofold greater in the fed versus fasted state compared with 2.8-and 2.5-fold greater in Japanese patients, and fed-state t max values of 4.0 versus 6.3 h, respectively [17].…”

“…In addition, darolutamide is different from other new-generation nonsteroidal AR antagonists with respect to its negligible blood-brain barrier penetration [14][15][16]. In early-phase clinical trials with Western mCRPC patients, darolutamide has shown a good safety profile and significant reductions in PSA levels [13,[17][18][19].…”

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

“…Another promising AR antagonist in clinical development is ODM-201, which is reported to be more potent that enzalutamide in inhibiting AR nuclear translocation (Moilanen et al 2015). Moreover, ODM-201 potentially has the added benefit of activity against AR mutants commonly found in CRPC, namely, T878A, W742L and F877L mutant (Fizazi et al 2014, Moilanen et al 2015.…”

Muscle and bone effects of androgen deprivation therapy: current and emerging therapies

“…Abiraterone, an irreversible and selective inhibitor of cytochrome p-450-17 to suppress adrenal and intratumoral androgen synthesis, and enzalutamide, an androgen receptor antagonist, have both been shown in landmark studies in men with castration-resistant prostate cancer to improve overall survival and progression-free survival (de Bono et al 2011, Scher et al 2012. More recently, a novel highaffinity androgen receptor inhibitor ODM-201 showed a favorable safety profile and disease suppression in a phases 1-2 study (Fizazi et al 2014). Results from these studies confirm that the androgen receptor and androgen receptor signaling play a pivotal role in progressive prostate cancer despite castrate levels of serum testosterone induced by conventional ADT.…”