Pharmacokinetics and Safety Study of Pelabresib in Patients With Advanced Malignancies and Hepatic Impairment

NCT07422610 | Not Yet Recruiting Phase 1

• 2 other identifiers: CDAK539A121032025-521001-40-00
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Advanced Malignancies and Hepatic Impairment

Keywords

Hepatic impairment (HI); Moderate or severe hepatic impairment; Advanced malignancies; Pharmacokinetics (PK); Bromodomain and extraterminal (BET)

Outcome Measures

Primary Outcomes (5)

• Area Under the Curve from 0 to 24 hours on Day 14 (AUC₀-24h,D14) of pelabresib at steady state per study group

  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.

  Cycle 1 Day 14: 0, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose (1 cycle = 21 days)

• Maximum Plasma Concentration on Day 14 (Cmax,D14) of pelabresib at steady state per study group

  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.

  Cycle 1 Day 14 (1 cycle = 21 days)

• Apparent Clearance (CL/F) of pelabresib at steady state per study group

  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.

  Cycle 1 Day 14 (1 cycle = 21 days)

• Apparent Volume of Distribution (V/F) of pelabresib at steady state per study group

  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.

  Cycle 1 Day 14 (1 cycle = 21 days)

• Terminal Half-Life (T½) of pelabresib at steady state per study group

  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.

  Cycle 1 Day 14 (1 cycle = 21 days)

Secondary Outcomes (11)

• 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)

Study Arms (2)

Group 1 (normal hepatic function)

EXPERIMENTAL

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.

Drug: pelabresib

Group 2 (moderate or severe HI)

EXPERIMENTAL

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.

Drug: pelabresib

Interventions

pelabresib DRUG

pelabresib 125 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break

Also known as: DAK539 (formerly CPI-0610)

Group 1 (normal hepatic function); Group 2 (moderate or severe HI)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2026
• First Posted: February 20, 2026
• Study Start (Estimated): May 18, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): September 4, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share