pelabresib: pelabresib 125 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Key Inclusion Criteria:
* 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:
1. Platelet count ≥ 150 × 109 /L in the absence of thrombopoietic factors or transfusions within 2 weeks of the screening assessment
2. Absolute neutrophil count (ANC) ≥ 1 × 109 /L in the absence of granulocyte growth factors
3. Adequate renal function (creatinine clearance of ≥30 mL/min, calculated using Cockcroft-Gault formula)
4. 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:
1. 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
2. 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
Key Exclusion Criteria:
* 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.
Primary outcome measure(s)
Area Under the Curve from 0 to 24 hours on Day 14 (AUC₀-24h,D14) of pelabresib at steady state per study group — 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 — 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 — 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 — 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 — 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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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