A Phase 1b, Open-Label, Multicenter Study to Evaluate the Pharmacokinetic Profile of Pelabresib (DAK539/CPI-0610) in Patients With Advanced Malignancies and Hepatic Impairment
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 10
- 主要终点
- Area Under the Curve from 0 to 24 hours on Day 14 (AUC₀-24h,D14) of pelabresib at steady state per study group
研究概览
简要总结
The primary purpose of this study is to evaluate the impact of hepatic function on the pharmacokinetic (PK) profile of pelabresib in participants with advanced malignancies who have either hepatic impairment (HI) or normal liver function. To reduce participant burden and maximize benefit, the PK of pelabresib will be assessed at steady-state rather than after a single dose, avoiding treatment-free washout periods.
详细描述
This study consists of 2 main parts: Part 1 will assess the PK characteristics of pelabresib in participants with hepatic impairment versus normal hepatic function, and during Part 2, extended treatment with pelabresib may be offered in case of clinical benefit, as assessed by the investigator.
A participant is considered to have started the study and entered the screening period upon signing the informed consent form (ICF). Enrollment occurs when participant receive their first dose of study treatment via the IRT system. A participant is considered to have completed the study if they have completed all phases of the study including the end of treatment (EOT) and 30-day safety follow-up visits. Participants with hematological malignancies will be followed up every 3 months beyond EOT.
Part 1: Impact of hepatic impairment on pelabresib PK
In Part 1, the PK characteristics of pelabresib will be investigated in participants with advanced malignancies comprising 2 different study groups according to their hepatic function:
- Group 1 includes participants with normal hepatic function
- Group 2 includes participants with moderate or severe HI
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is at least 18 and not older than 75 years of age at the time of signing the informed consent.
- •Group 1 only: There is a matching participant in Group 2 and an enrollment slot is available for the Group 1 participant.
- •Has a confirmed documented diagnosis of an advanced malignancy for which no standard and/or curative treatment options are available.
- •Has the following acceptable laboratory assessments prior to the first dose of study treatment:
- •Platelet count ≥ 150 × 109 /L in the absence of thrombopoietic factors or transfusions within 2 weeks of the screening assessment
- •Absolute neutrophil count (ANC) ≥ 1 × 109 /L in the absence of granulocyte growth factors
- •Adequate renal function (creatinine clearance of ≥30 mL/min, calculated using Cockcroft-Gault formula)
- •Peripheral blood blast count < 5%. Assessment of blasts in bone marrow is not mandatory at screening, however, blasts must be <5% if the assessment is performed.
- •Has a life expectancy ≥3 months.
- •Has fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy .
- •Hepatic function:
- •Is in Group 1 and is classified as having normal hepatic function based on NCI-ODWG criteria (i.e., total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) ≤ ULN); or
- •Is in Group 2 and has stable moderate or severe HI as defined by NCI ODWG criteria:
- •moderate HI: total bilirubin >1.5 × to 3 × ULN, and any AST value
- •severe HI: total bilirubin > 3 × ULN, and any AST value
排除标准
- •Has a history of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical class.
- •Has any other medical condition which, in the investigator's opinion, makes the participant unsuitable for the study.
- •Is a female participant who is pregnant (confirmed by a pregnancy test at screening) or is breastfeeding.
- •Is a woman of childbearing potential (WOCBP) who does not agree to follow the contraceptive guidance during the treatment period and for at least 184 days after the last dose of study treatment, and who does not agree to refrain from donating eggs during this period.
- •Has esophageal variceal bleeding within the past 2 months prior to the first dose of pelabresib.
- •Has an active clinically significant infection.
- •Has impaired cardiac function or clinically significant cardiac diseases
- •Has a GI tumor, impaired GI function, GI disease, or significant resection of stomach or other portion of the GI tract that could alter the absorption of pelabresib, including any unresolved nausea, vomiting, or diarrhea.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Group 2 (moderate or severe HI)
Part 1: Participants receive pelabresib 125 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break (1 cycle = 21 days).
If clinical benefit is observed, treatment continues in Part 2 until end of study (EOS), discontinuation criteria, or alternative access.
干预措施: pelabresib (Drug)
Group 1 (normal hepatic function)
Part 1: Participants receive pelabresib 125 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break (1 cycle = 21 days).
If clinical benefit is observed, treatment continues in Part 2 until end of study (EOS), discontinuation criteria, or alternative access.
干预措施: pelabresib (Drug)
结局指标
主要结局
Area Under the Curve from 0 to 24 hours on Day 14 (AUC₀-24h,D14) of pelabresib at steady state per study group
时间窗: Cycle 1 Day 14: 0, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (1 cycle = 21 days)
Venous whole blood samples will be collected for pharmacokinetics characterization. AUC₀-24h,D14 of pelabresib at steady state per study group will be listed and summarized using descriptive statistics.
Maximum Plasma Concentration on Day 14 (Cmax,D14) of pelabresib at steady state per study group
时间窗: Cycle 1 Day 14 (1 cycle = 21 days)
Venous whole blood samples will be collected for pharmacokinetics characterization. Cmax,D14 of pelabresib at steady state per study group will be listed and summarized using descriptive statistics.
Apparent Clearance (CL/F) of pelabresib at steady state per study group
时间窗: Cycle 1 Day 14 (1 cycle = 21 days)
Venous whole blood samples will be collected for pharmacokinetics characterization. CL/F of pelabresib at steady state per study group will be listed and summarized using descriptive statistics.
Apparent Volume of Distribution (V/F) of pelabresib at steady state per study group
时间窗: Cycle 1 Day 14 (1 cycle = 21 days)
Venous whole blood samples will be collected for pharmacokinetics characterization. V/F of pelabresib at steady state per study group will be listed and summarized using descriptive statistics.
Terminal Half-Life (T½) of pelabresib at steady state per study group
时间窗: Cycle 1 Day 14 (1 cycle = 21 days)
Venous whole blood samples will be collected for pharmacokinetics characterization. T½ of pelabresib at steady state per study group will be listed and summarized using descriptive statistics.
次要结局
- Maximum Plasma Concentration on Day 1 (Cmax,D1) of pelabresib per study group(Cycle 1 Day 1 (1 cycle = 21 days))
- Area Under the Curve from 0 to 24 hours on Day 1 (AUC₀-24h,D1) of pelabresib per study group(Cycle 1 Day 1: 0, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (1 cycle = 21 days))
- Trough Concentration on Day 14 (Ctrough,D14) of pelabresib per study group(Cycle 1 Day 14: predose (1 cycle = 21 days))
- Accumulation Ratio (Rac) of pelabresib per study group(Cycle 1: Day 14 compared to Day 1 (1 cycle = 21 days))
- Time to Maximum Concentration (Tmax) of pelabresib per study group(Cycle 1: Day 1 and Day 14 (1 cycle = 21 days))
- Terminal Half-Life (T½) of pelabresib per study group(Cycle 1 Day 1 (1 cycle = 21 days))
- Fraction Unbound (fu) of pelabresib per study group(Cycle 1 Day 14: 0, 2, and 8 hours postdose (1 cycle = 21 days))
- fu-adjusted AUC of pelabresib per study group(Cycle 1: Day 1 and Day 14 (1 cycle = 21 days))
- fu-adjusted Cmax of pelabresib per study group(Cycle 1: Day 1 and Day 14 (1 cycle = 21 days))
- fu-adjusted Ctrough of pelabresib per study group(Cycle 1 Day 1 and Day 14: predose (1 cycle = 21 days))
- Number of Participants with adverse events (AEs), serious AEs (SAEs)(Through study completion, an average of 28 months)