Pelabresib plus ruxolitinib for adults with myelofibrosis

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

This trial will see if adding pelabresib to ruxolitinib helps adults with primary myelofibrosis or post‑PV/post‑ET myelofibrosis who have not previously taken JAK inhibitor therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 460 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: ruxolitinib
• Locations: 6 sites (Berkeley Heights, New Jersey and 5 other locations)
• Trial ID: NCT07357727 on ClinicalTrials.gov

What this trial studies

This is a Phase 3, randomized study comparing pelabresib plus ruxolitinib to ruxolitinib with placebo in patients with primary or post‑polycythemia vera/post‑essential thrombocythemia myelofibrosis who are JAK inhibitor‑naive. Treatment is given in 21‑day cycles with pelabresib or placebo administered for 14 days and ruxolitinib given continuously, and participants are followed for safety and efficacy after treatment. Key entry requirements include intermediate‑1 to high DIPSS risk, spleen volume ≥450 cm3, total symptom score ≥15, platelet count ≥100 x109/L, blasts <5%, and ECOG 0–2. The study includes screening, an on‑treatment period until discontinuation for progression or toxicity, a 30‑day safety follow‑up, and a longer efficacy follow‑up phase.

Who should consider this trial

Good fit: Ideal candidates are adults with confirmed primary MF, post‑PV MF, or post‑ET MF who are JAK inhibitor‑naive, meet DIPSS risk and spleen/symptom criteria (e.g., spleen ≥450 cm3 and TSS ≥15), have platelets ≥100 x109/L, blasts <5%, and ECOG 0–2.

Not a fit: Patients who previously received JAK inhibitor therapy, have had a splenectomy, have platelets <100 x109/L, peripheral blasts ≥5%, or otherwise meet exclusion criteria are unlikely to be eligible or benefit from this protocol.

Why it matters

Potential benefit: If successful, adding pelabresib to ruxolitinib could improve treatment outcomes compared with ruxolitinib alone, potentially reducing spleen size and relieving symptoms more effectively.

How similar studies have performed: Earlier phase studies combining pelabresib with ruxolitinib showed promising signs of improved spleen and symptom responses, but this Phase 3 tests those findings in a larger, randomized setting.

Eligibility criteria

Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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

Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

Berkeley Heights, New Jersey and 5 other locations

• Summit Medical Group — Berkeley Heights, New Jersey, United States (Recruiting)
• Novartis Investigative Site — Seoul, Yangcheon Gu, South Korea (Recruiting)
• Novartis Investigative Site — Seoul, South Korea (Recruiting)
• Novartis Investigative Site — Seoul, South Korea (Recruiting)
• Novartis Investigative Site — Seoul, South Korea (Recruiting)
• Novartis Investigative Site — Genolier, Switzerland (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Pelabresib; Ruxolitinib; Adult participants; Myelofibrosis