We assessed the real-world effectiveness of darolutamide in a racially/ethnically diverse population of M1-CRPC....AR mutations that emerged or increased in ctDNA allele fraction while on darolutamide included L702H, H875Y, H100Q, D891H, T878A, L329W and AR copy number gain, suggesting a possible role in darolutamide resistance….However, prior resistance to enzalutamide/apalutamide and/or associated AR mutations can significantly decrease the likelihood of benefit from darolutamide.