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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignancies and Hepatic Impairment
• Intervention / Treatment: Drug: pelabresib

Detailed Description

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

Following completion of Part 1, participants can directly proceed to Part 2

Part 2: Continued treatment After completing Part 1, in case of clinical benefit, participants can continue with pelabresib treatment in Part 2 until the end of study (EOS) is reached, until the participant meets discontinuation criteria, or until they receive pelabresib treatment via alternative means of access, whichever occurs first. Clinical benefit is determined by the investigator.

End of treatment visit An EOT visit is required for all participants within 7 days of the last dose of pelabresib treatment (or within 7 days of the decision to discontinue treatment, if the decision was made > 7 days after the last dose).

30-day safety follow-up All participants will be followed up for AEs and serious AEs (SAEs) for 30 days (±3 days) following the last dose of pelabresib. If the participant starts another anticancer treatment or switches to pelabresib treatment via an alternative source (e.g., in an extension study or commercially available pelabresib), the safety follow-up will end at the time of the first administration of the respective treatment.

Leukemic transformation follow-up for participants with hematological malignancies After the EOT visit and the 30-Day safety follow-up visit, participants with hematological malignancies will be followed up every 3 months for leukemic transformation until the overall end of the study, confirmation of AML, withdrawal of consent, loss to follow-up, or death, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com

Study Locations

• Italy
  • TO
    • Candiolo, TO, Italy, 10060
      • Recruiting
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: pelabresib; pelabresib 125 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break; Other Names: DAK539 (formerly CPI-0610)
Experimental: 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.	Drug: pelabresib; pelabresib 125 mg orally (PO) once daily (QD) for 14 days, followed by a 7-day break; Other Names: DAK539 (formerly CPI-0610)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration on Day 1 (Cmax,D1) of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. Cmax,D1 of pelabresib per study group will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected for pharmacokinetics characterization. AUC₀-24h,D1 of pelabresib per study group will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected for pharmacokinetics characterization. Ctrough,D14 of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1 Day 14: predose (1 cycle = 21 days)
Accumulation Ratio (Rac) of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. Rac of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1: Day 14 compared to Day 1 (1 cycle = 21 days)
Time to Maximum Concentration (Tmax) of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. Tmax of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1: Day 1 and Day 14 (1 cycle = 21 days)
Terminal Half-Life (T½) of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. T½ of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1 Day 1 (1 cycle = 21 days)
Fraction Unbound (fu) of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. fu of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1 Day 14: 0, 2, and 8 hours postdose (1 cycle = 21 days)
fu-adjusted AUC of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. fu-adjusted AUC of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1: Day 1 and Day 14 (1 cycle = 21 days)
fu-adjusted Cmax of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. fu-adjusted Cmax of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1: Day 1 and Day 14 (1 cycle = 21 days)
fu-adjusted Ctrough of pelabresib per study group	Venous whole blood samples will be collected for pharmacokinetics characterization. fu-adjusted Ctrough of pelabresib per study group will be listed and summarized using descriptive statistics.	Cycle 1 Day 1 and Day 14: predose (1 cycle = 21 days)
Number of Participants with adverse events (AEs), serious AEs (SAEs)	Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.	Through study completion, an average of 28 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2026
• Primary Completion (Estimated): June 28, 2028
• Study Completion (Estimated): August 2, 2028

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Advanced malignancies; Pharmacokinetics (PK); Hepatic impairment (HI); Moderate or severe hepatic impairment; Bromodomain and extraterminal (BET)
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular
• Other Study ID Numbers: CDAK539A12103; 2025-521001-40-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No