Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Étude de pharmacocinétique et de sécurité du Pelabresib chez les patients atteints de tumeurs malignes avancées et d'insuffisance hépatique

17 septembre 2026 mis à jour par: Novartis Pharmaceuticals

Étude de phase 1b, ouverte, multicentrique pour évaluer le profil pharmacocinétique du pelabresib (DAK539/CPI-0610) chez des patients atteints de tumeurs malignes avancées et d'insuffisance hépatique

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

24

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • Espagne
      • Barcelona, Espagne, 08023
        • Recrutement
        • Novartis Investigative Site
      • Madrid, Espagne, 28040
        • Recrutement
        • Novartis Investigative Site
      • Madrid, Espagne, 28050
        • Recrutement
        • Novartis Investigative Site
    • Madrid
      • Pozuelo de Alarcón, Madrid, Espagne, 28223
        • Recrutement
        • Novartis Investigative Site
  • France
      • Bordeaux, France, 33075
        • Recrutement
        • Novartis Investigative Site
      • Saint-Herblain, France, 44805
        • Recrutement
        • Novartis Investigative Site
  • Italie
    • MI
      • Milan, MI, Italie, 20132
        • Recrutement
        • Novartis Investigative Site
      • Milan, MI, Italie, 20141
        • Recrutement
        • Novartis Investigative Site
    • TO
      • Candiolo, TO, Italie, 10060
        • Recrutement
        • Novartis Investigative Site
  • Royaume-Uni
      • London, Royaume-Uni, W12 0HS
        • Recrutement
        • Novartis Investigative Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La 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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: pelabresib

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

Autres noms:
  • DAK539 (anciennement CPI-0610)
Expérimental: 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.
Médicament: pelabresib

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

Autres noms:
  • DAK539 (anciennement CPI-0610)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Area Under the Curve from 0 to 24 hours on Day 14 (AUC₀-24h,D14) of pelabresib at steady state per study group
Délai: 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.
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
Délai: 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.
Cycle 1 Day 14 (1 cycle = 21 days)
Apparent Clearance (CL/F) of pelabresib at steady state per study group
Délai: 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.
Cycle 1 Day 14 (1 cycle = 21 days)
Apparent Volume of Distribution (V/F) of pelabresib at steady state per study group
Délai: 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.
Cycle 1 Day 14 (1 cycle = 21 days)
Terminal Half-Life (T½) of pelabresib at steady state per study group
Délai: 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.
Cycle 1 Day 14 (1 cycle = 21 days)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Maximum Plasma Concentration on Day 1 (Cmax,D1) of pelabresib per study group
Délai: Cycle 1 Day 1 (1 cycle = 21 days)

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
Délai: Cycle 1 Day 1: 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,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
Délai: Cycle 1 Day 14: predose (1 cycle = 21 days)

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
Délai: Cycle 1: Day 14 compared to Day 1 (1 cycle = 21 days)

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
Délai: Cycle 1: Day 1 and Day 14 (1 cycle = 21 days)

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
Délai: Cycle 1 Day 1 (1 cycle = 21 days)

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
Délai: Cycle 1 Day 14: 0, 2, and 8 hours postdose (1 cycle = 21 days)

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
Délai: Cycle 1: Day 1 and Day 14 (1 cycle = 21 days)

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
Délai: Cycle 1: Day 1 and Day 14 (1 cycle = 21 days)

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
Délai: Cycle 1 Day 1 and Day 14: predose (1 cycle = 21 days)

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)
Délai: Through study completion, an average of 28 months

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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis Pharmaceuticals

Les enquêteurs

  • Directeur d'études: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

19 mai 2026

Achèvement primaire (Estimé)

28 juin 2028

Achèvement de l'étude (Estimé)

2 août 2028

Dates d'inscription aux études

Première soumission

22 janvier 2026

Première soumission répondant aux critères de contrôle qualité

12 février 2026

Première publication (Réel)

20 février 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

17 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CDAK539A12103
  • 2025-521001-40-00 (Identificateur de registre: EU CT Number)
  • 2025 (Subvention/contrat des NIH des États-Unis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner