A Phase I/II Open-Label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer in China
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 27
- 主要终点
- Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
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 daily oral dosing with HP518,selecting the RP2D of HP518 based on assessments of patients with progressive mCRPC in dose-escalation phase
详细描述
This First in Human dose escalation and expansion study of HP518 in patients with progressive mCRPC after NHA and chemotherapy is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide preliminary efficacy for the reference of 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
- •Male, age ≥18
- •Patients with androgen receptor (AR) ligand binding domain (LBD) activation mutations (the dose expansion part of stage II)
- •Has histologically confirmed adenocarcinoma of the prostate, but there are no known significant neuroendocrine differentiation or small cell characteristics.
- •Has metastatic disease documented by 2 or more bone lesions by bone scan or soft tissue disease progression observed by CT/MRI at the beginning of study.
- •the progression of the disease after receiving at least one new endocrine therapy and progressing with at least first-line chemotherapy.
- •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
- •Combination of research or commercially available drugs targeting AR
- •Has had any other anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177LuPSMA-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.
研究组 & 干预措施
Part 1 - Dose Escalation, 400mg/d (Cohort1)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 1 - Dose Escalation 500mg/d (Cohort 2)
Oral tablet(s), once daily in 28-day cycles
干预措施: HP518 - Dose Escalation (Drug)
Part 2 - Dose Expansion Oral tablet(s)
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
Incidence of vital signs 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 of orally administered HP518 (Part 1)
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 drugorally administered HP518 (Part 1)
时间窗: 28 DAYS
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
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 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 of orally administered HP518 (Part 1)
PSA50 response rate
时间窗: 12 weeks
Proportion of patients showing a PSA decline by ≥50% between baseline and Week 12 of dosing with HP518.
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 of orally administered HP518 (Part 1)
次要结局
- apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)(12 weeks)
- oral clearance (CL/F)(12 weeks)
- According to PCWG3(8 weeks)
- According to PCWG3, evaluate time to PSA progression(Through study completion, an average of 1 year)
- area under the concentration-time curve (AUC)(12 weeks)
- Maximum concentration (Cmax)(12 weeks)
- Time to maximum concentration (Tmax)(12 weeks)
- Apparent terminal elimination half-life (T1/2)(12 weeks)
- Time to radiographic progression by investigator PCWG3 definition(Through study completion, an average of 1 year)
- Evaluate the modified best overall response mBOR by investigator(Through study completion, an average of 1 year)
- analyze the efficacy of patients with different AR phenotypes(Part 2)(Through study completion, an average of 1 year)