Pelabresib added to ruxolitinib for Japanese adults with myelofibrosis

A Phase 1b Study of Pelabresib (DAK539) add-on to Stable Dose of Ruxolitinib in Japanese Adult Patients With Myelofibrosis

This Phase 1b study will test whether adding pelabresib to a stable dose of ruxolitinib is safe and shows early signs of benefit for Japanese adults with myelofibrosis.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: ruxolitinib
• Locations: 6 sites (Kamogawa, Chiba and 5 other locations)
• Trial ID: NCT07340138 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter Phase 1b study enrolls three to nine Japanese adults with primary or secondary myelofibrosis who are already on a stable dose of ruxolitinib. After up to 28 days of screening, participants receive pelabresib in addition to ruxolitinib and are monitored for safety, pharmacokinetics, and preliminary efficacy. Treatment continues until disease progression, unacceptable toxicity, death, or withdrawal, followed by a 30-day safety visit and long-term follow-up approximately every 12 weeks for at least three years from first dose and two years after last dose. The protocol includes ongoing assessment for leukemic transformation and will continue until all participants complete follow-up or pelabresib becomes available through post-trial access or reimbursement in Japan.

Who should consider this trial

Good fit: Ideal candidates are Japanese adults with DIPSS intermediate‑1, intermediate‑2, or high‑risk primary or secondary myelofibrosis who have been on a stable ruxolitinib dose (5–25 mg twice daily) for at least eight weeks, have palpable or imaging-confirmed splenomegaly, and have platelet counts ≥100 × 10^9/L.

Not a fit: Patients unlikely to benefit include those not taking ruxolitinib, with platelet counts below 100 × 10^9/L, with contraindications or prior intolerance to the study drugs, or who cannot attend the Japan investigational sites.

Why it matters

Potential benefit: If successful, the combination could offer improved disease control or symptom relief for patients who remain symptomatic on ruxolitinib alone.

How similar studies have performed: Previous non-Japanese early-phase trials combining pelabresib (a BET inhibitor) with ruxolitinib have shown promising spleen size reductions and symptom improvements, though larger studies are required to confirm benefit.

Eligibility criteria

Key Inclusion Criteria:

* Participants have diagnosis of primary myelofibrosis (PMF), post-polycythemia vera MF (Post-PV MF) or post-essential thrombocythemia MF (Post-ET MF) according to the International Consensus Classification (ICC) for Myeloid Neoplasms and Acute Leukemias 2022.
* DIPSS risk category intermediate-1, intermediate-2 or high-risk at screening.
* Participants currently treated with ruxolitinib monotherapy AND who are likely to benefit from the addition of pelabresib to ruxolitinib in the opinion of the investigator.
* Receiving ruxolitinib at a stable dose (5 to 25 mg BID) for at least 8 weeks prior to the first dose of pelabresib.
* Palpable spleen (spleen length below left costal margin \[LCM\] must be recorded) or documented splenomegaly by MRI or CT (image report must be recorded) at screening.
* Platelet count ≥ 100 × 10\^9/L in the absence of growth factor support (including thrombopoietin mimetics/agonists) or platelet transfusions 4 weeks prior to the first dose of pelabresib.
* Blasts \< 5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening.

Key Exclusion Criteria:

* Prior splenectomy at any time or splenic irradiation in the previous 6 months
* Prior hematopoietic cell transplant or participants anticipated to receive a hematopoietic cell transplant within 24 weeks from the first dose of pelabresib.
* Blasts ≥ 5% in bone marrow if results available at screening or history of accelerated phase or leukemic transformation.
* History of a malignancy (other than MF, PV or ET) except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to start of pelabresib, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years
* Received any approved or investigational agent for the treatment of MF except ruxolitinib within 14 days of first dose of pelabresib or within 5 half-lives of the approved or investigational agent, whichever is longer.

Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

Kamogawa, Chiba and 5 other locations

• Novartis Investigative Site — Kamogawa, Chiba, Japan (Recruiting)
• Novartis Investigative Site — Sapporo, Hokkaido, Japan (Recruiting)
• Novartis Investigative Site — Kamakura, Kanagawa, Japan (Recruiting)
• Novartis Investigative Site — Bunkyo Ku, Tokyo, Japan (Recruiting)
• Novartis Investigative Site — Chūō, Yamanashi, Japan (Recruiting)
• Novartis Investigative Site — Kumamoto, Japan (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

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