Phase I clinical trial of HC‐1119: A deuterated form of enzalutamide

Abstract The purpose of our study was to investigate the safety, pharmacokinetics (PK), and initial antitumor efficacy of HC‐1119 in patients with metastatic castration‐resistant prostate cancer (mCRPC). Eligible mCRPC patients were included in our study (NCT 03774056) 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 tumor response was also assessed. Twenty‐four patients were enrolled in part A and 19 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 C max 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.