Recruiting
Phase 3

Pelabresib & Ruxolitinib

Sponsor:

Novartis Pharmaceuticals

Code:

NCT07357727

Conditions

Primary Myelofibrosis (PMF)

Post-polycythemia Vera Myelofibrosis (PPV-MF)

Post-essential Thrombocythemia Myelofibrosis (PET-MF)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pelabresib

Ruxolitinib

Placebo

Study Details

Brief 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.

Conditions

Primary Myelofibrosis (PMF)

Post-polycythemia Vera Myelofibrosis (PPV-MF)

Post-essential Thrombocythemia Myelofibrosis (PET-MF)

Study ID

NCT07357727

Start date

Jun 16, 2026

Status verified date

Aug, 2026

Completion date

Dec 27, 2030

Anticipated

Primary completion date

May 17, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

460 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: Pelabresib + Ruxolitinib

Participants in this arm receive pelabresib (DAK539) orally once daily for 14 days of each 21-day cycle, in combination with ruxolitinib, which is taken orally twice daily throughout each cycle. Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment.

placebo comparator: Arm 2: Placebo + Ruxolitinib

Participants in this arm receive a matching placebo orally once daily for 14 days of each 21-day cycle, together with ruxolitinib, which is also taken orally twice daily throughout each cycle.

Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment.

Interventions

Pelabresib

Pelabresib monohydrate tablets

Ruxolitinib

Ruxolitinib phosphate tablets

Placebo

Matches pelabresib

Primary outcome measure

  • Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline total symptom score (TSS) ≥ 25 [ Time Frame: Week 24 ]
  • Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 25 [ Time Frame: Baseline, Week 24 ]
  • Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline TSS ≥ 15 [ Time Frame: Week 24 ]
  • Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 15 [ Time Frame: Baseline, Week 24 ]

Central Contacts and Locations

Central contacts

Novartis Pharmaceuticals

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

Novartis Pharmaceuticals

+41613241111novartis.email@novartis.com

Locations

Yale University School Of Medicine

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Farah Fasihuddin

farah.fasihuddin@yale.edu

Principal Investigator:

Nikolai Podoltsev

The Anderson Family Cancer Institute

Recruiting

Jupiter, Florida, United States, 33458

Contacts

Christine Leonard

christine.leonard@jupitermed.com

Principal Investigator:

Ryan Devine

Winship Cancer Institute of Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Danielle Alexander

danielle.oliver@emory.edu

Principal Investigator:

Anthony Michael Hunter

Summit Medical Group Oncology

Recruiting

Berkeley Heights, New Jersey, United States, 07922

Contacts

Michelle Mackenzie

973-436-1755mmackenzie@summithealth.com

Principal Investigator:

Lalitha Anand

The Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43221

Contacts

Hannah Davis

Hannah.Davis@osumc.edu

Principal Investigator:

Andrew Srisuwananukorn

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Maria Pinsoy

mbpinsoy@mdanderson.org

Principal Investigator:

Prithviraj Bose

More Information

Sponsor

Novartis Pharmaceuticals

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Keywords

  • Pelabresib (DAK539)
  • Ruxolitinib
  • Adult participants
  • Myelofibrosis (MF)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Novartis Pharmaceuticals on 2026-09-01.