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

NCT07357727 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CDAK539A123032025-523555-66-00
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 4

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-essential Thrombocythemia Myelofibrosis (PET-MF); Post-polycythemia Vera Myelofibrosis (PPV-MF)

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline total symptom score (TSS) ≥ 25

  Spleen Response (SVR35) is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review in participants with baseline TSS ≥ 25.

  Week 24

• Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 25

  Symptom improvement at Week 24 is defined as the absolute change from baseline in the total symptom score (TSS) at Week 24, as measured by the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) in participants with baseline TSS ≥ 25.

  Baseline, Week 24

• Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline TSS ≥ 15

  Spleen Response (SVR35) is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review in participants with baseline TSS ≥ 15.

  Week 24

• Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 15

  Symptom improvement at Week 24 is defined as the absolute change from baseline in the total symptom score (TSS) at Week 24, as measured by the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) in participants with baseline TSS ≥ 15.

  Baseline, Week 24

Secondary Outcomes (24)

• Number of Participants with Splenic Response (SVR35) by Central Radiology Reads over time

  Week 12, Week 36, Week 48 and every 12 weeks thereafter till End of Study (an average of 3 years)

• Absolute change from baseline and percentage change from baseline in spleen volume over time

  Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)

• Time to first SVR35 response

  From date of randomization to the date of first SVR35 response, assessed up to approximately 3 years

• Duration of first SVR35 response

  From first SVR35 response to loss of response, assessed up to approximately 3 years

• Number of Participants with TSS50 response at Week 24

  Week 24

Study Arms (2)

Arm 1: Pelabresib + Ruxolitinib

EXPERIMENTAL

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.

Drug: Pelabresib; Drug: Ruxolitinib

Arm 2: Placebo + Ruxolitinib

PLACEBO COMPARATOR

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.

Drug: Ruxolitinib; Drug: Placebo

Interventions

Pelabresib DRUG

Pelabresib monohydrate tablets

Also known as: DAK539

Arm 1: Pelabresib + Ruxolitinib

Ruxolitinib DRUG

Ruxolitinib phosphate tablets

Also known as: INC424

Arm 1: Pelabresib + Ruxolitinib; Arm 2: Placebo + Ruxolitinib

Placebo DRUG

Matches pelabresib

Arm 2: Placebo + Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Seoul, Yangcheon Gu, 07985, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 03080, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 05505, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 06591, South Korea

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

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

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: January 22, 2026
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 17, 2028
• Study Completion (Estimated): December 27, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

KR (4)