Across 140 biomarker-evaluable phase 1/2 pts with =1 month of prostate-specific antigen (PSA) follow-up, 26 with AR T878A/S and/or H875Y mutations had best PSA declines =50% (PSA50) and =30% (PSA30) of 46% and 58%, respectively...Of 7 RECIST-evaluable pts with AR T878A/S and/or H875Y mutations, 6 had tumor shrinkage (2 with confirmed partial responses)...ARV-110, a novel AR protein degrader, demonstrates clinical activity in a post-NHA, heavily pretreated mCRPC pt population, with greatest PSA50 activity and RECIST responses in pts with AR T878 and/or H875 mutations, likely representing a particularly ARV-110–sensitive population.