The purpose of this study was to investigate the safety, pharmacokinetics (PK), and initial anti-tumor efficacy of HC-1119 in patients with metastatic castration-resistant prostate cancer (mCRPC). Eligible mCRPC patients were included in this study (NCT03774056) with two parts. Part A was a dose escalation study in which patients received a dose escalation of HC-1119 (40, 80, 160, and 200 mg/day). Part B was a dose expansion study in which patients received HC-1119 at the dose of 80 and 160 mg. Safety assessment and pharmacokinetic samplings were performed for all patients at the given time points; preliminary tumour response was also assessed.Twenty-four patients were enrolled in part A and nineteen patients in part B, respectively. HC-1119 was safe, well tolerated and no dose-limiting toxicity was observed. Fatigue was the most common treatment-related adverse event and no seizures were observed. At the dose levels of 40, 80, and 160 mg, the AUC and Cmax of HC-1119 in plasma increased almost dose-proportionally at the steady state in mCRPC patients. Maximum prostate-specific antigen (PSA) response rates (≥50% reduction from the baseline) in dose escalation and dose expansion cohorts were 77% and 75%, respectively; the overall disease control rate (22 patients available for imaging analysis) was 72.7%, with PR in 4 patients, SD in 12 patients, and PD in 6 patients; the 2-year overall survival rate in patients from Part B was 56.8%. HC-1119 was safe, well tolerated, and efficacious and HC-1119 at 80 mg/day is recommended for further studies. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.