A Phase 1 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 5
- 主要终点
- Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug
研究概览
简要总结
The overall objective of this Phase 1 study is to evaluate the safety, PK, and anti-tumor activity of 12 weeks of daily oral dosing with HP518 after selecting the RP2D of HP518 based on assessments of multiple dose escalation in patients with progressive mCRPC.
详细描述
This First in Human dose escalation and expansion study of HP518 in patients with mCRPC is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide necessary information for efficacy analysis in future studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Has histologically confirmed adenocarcinoma of the prostate.
- •Has metastatic disease at study entry documented by 2 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
- •Has disease progression while receiving any ADT, androgen biosynthesis inhibitors, or second-generation AR inhibitors.
- •Must have recovered from toxicities related to any prior treatments
- •Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.
- •ECOG performance status score of 0 to 1.
排除标准
- •Has received more than 1 line of chemotherapy for prostate cancer.
- •Use of enzalutamide, and/or other second-generation AR inhibitors and/or abiraterone as follows:
- •Received any agent within 4 weeks prior to the start of study drug.
- •Discontinued agent without evidence of radiographic or PSA progression.
- •Has had any anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177Lu-PSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP
- •Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
- •Has significant cardiovascular disease.
- •Use of an investigational agent, without evidence of radiographic or PSA progression, within 4 weeks prior to the first dose of HP518 or a period required by local regulation, whichever is longer.
研究组 & 干预措施
Part 1 - Dose Escalation, 25mg/d (Cohort 1)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 1 - Dose Escalation 100mg/d (Cohort 2)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 1 - Dose Escalation 200mg/d (Cohort 3)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 1 - Dose Escalation 300mg/d (Cohort 4)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 1 - Dose Escalation 400mg/d (Cohort 5)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 1 - Dose Escalation 500mg/d (Cohort 6)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 2 - Dose Expansion
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose expansion (Drug)
结局指标
主要结局
Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug
时间窗: 28 days
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518.
时间窗: 12 weeks
Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness
时间窗: Through study completion, an average of 1 year
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
时间窗: Through study completion, an average of 1 year
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
时间窗: Time Frame: Through study completion, an average of 1 year
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
Incidence of ECG (PR, QRS, QT, and QTcF intervals) abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
时间窗: Through study completion, an average of 1 year
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
次要结局
- Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)(12 weeks)
- Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)(12 weeks)
- Assessment of PSA50 from baseline to after 4 and 8 weeks of dosing with HP518(8 weeks)
- Time to PSA progression using the PCWG3 definition (PSA >25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart)(Through study completion, an average of 1 year)
- Time to radiographic progression using the RECIST v1.1 and PCWG3 definition(Through study completion, an average of 1 year)
- Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline(Through study completion, an average of 1 year)
- Change in number of AR N-term-positive CTCs/ml from baseline to week 12(12 weeks)
- Genomic profiling using cfDNA(12 weeks)
- Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)(12 weeks)
- Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)(12 weeks)
- Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)(12 weeks)
- Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)(12 weeks)