RecruitingPhase 3NCT07357727

A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)

A Phase 3, Randomized, Double-blind, Active-control Study of Pelabresib (DAK539) and Ruxolitinib vs. Placebo and Ruxolitinib in Adult Patients With Myelofibrosis Who Are JAK Inhibitor Naive


Sponsor

Novartis Pharmaceuticals

Enrollment

460 participants

Start Date

May 15, 2026

Study Type

INTERVENTIONAL

Summary

The purpose of this trial is to evaluate whether treatment with pelabresib in combination with ruxolitinib leads to improved clinical outcomes compared to ruxolitinib alone in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF) who have not previously received Janus kinase (JAK) inhibitor therapy.


Eligibility

Min Age: 18 Years

Inclusion Criteria7

  • Participants have diagnosis of primary myelofibrosis (PMF) or post-polycythemia vera myelofibrosis (post-PV MF) or post-essential thrombocythemia myelofibrosis (post-ET MF) according to the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemias 2022
  • DIPSS risk category of intermediate-1, intermediate-2 or high-risk
  • Spleen volume ≥ 450 cm3 by CT or MRI scan (local read sufficient if no central read available)
  • Have an average TSS of ≥15 within 7 days prior to randomization, using MFSAF v. 4.0 (at least 4 out of 7 TSS assessments required for average calculation)
  • Participants with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Blasts <5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening
  • Platelet count ≥ 100 x 10\^9/L in the absence of growth factors or transfusions for the previous 4 weeks

Exclusion Criteria6

  • Prior splenectomy at any time or splenic irradiation in the previous 6 months
  • Prior hematopoietic cell transplant or participant anticipated to receive a hematopoietic cell transplant within 24 weeks from the date of randomization
  • Blasts ≥ 5% in bone marrow if results available at screening or history of accelerated phase (AP) or leukemic transformation
  • History of a malignancy (other than MF, PPV-MF or PET-MF) in the past 3 years in need of systemic treatment
  • Received any approved or investigational agent other than hydroxyurea or anagrelide for the treatment of MF within 14 days of first dose of study treatment or within 5 half-lives of the approved or investigational agent, whichever is longer
  • Prior treatment with any JAK inhibitor or Bromodomain and extraterminal domain (BET) inhibitor

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Interventions

DRUGPelabresib

Pelabresib monohydrate tablets

DRUGRuxolitinib

Ruxolitinib phosphate tablets

DRUGPlacebo

Matches pelabresib


Locations(4)

Novartis Investigative Site

Seoul, Yangcheon Gu, South Korea

Novartis Investigative Site

Seoul, South Korea

Novartis Investigative Site

Seoul, South Korea

Novartis Investigative Site

Seoul, South Korea

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NCT07357727