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 (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 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 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.

• Authors: Xiaoyu Li, Ke Cheng, Xinghai Li, Yuwen Zhou, Jiyan Liu, Hao Zeng, Yuanwei Chen, Xiao Liu, Ying Zhang, Yongsheng Wang, Feng Bi, Li Zheng
• Journal: International journal of cancer (Int J Cancer) Vol. 149 Issue 7 Pg. 1473-1482 (10 01 2021) ISSN: 1097-0215 [Electronic] United States
• PMID: 34109624 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 UICC.

Chemical References

• Antineoplastic Agents
• Benzamides
• Nitriles
• Phenylthiohydantoin
• enzalutamide

Topics

• Adenocarcinoma (drug therapy, secondary)
• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Benzamides (pharmacokinetics, therapeutic use)
• Follow-Up Studies
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Nitriles (pharmacokinetics, therapeutic use)
• Phenylthiohydantoin (pharmacokinetics, therapeutic use)
• Prognosis
• Prostatic Neoplasms (drug therapy, pathology)
• Tissue Distribution