Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis

NCT07340138 | Recruiting Phase 1

• 1 other identifier: CDAK539A11101
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief Summary

This Phase 1b, multicenter, open-label study aims to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of pelabresib as add-on to ruxolitinib in Japanese patients with myelofibrosis (MF).

Conditions

Post-essential Thrombocythemia Myelofibrosis (Post-ET MF); Primary Myelofibrosis (PMF); Post-polycythemia Vera Myelofibrosis (Post-PV MF)

Keywords

Pelabresib (DAK539); Ruxolitinib (INC424); Japanese adult participants; Myelofibrosis (MF)

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  A dose-limiting toxicity (DLT) is defined as any adverse event or abnormal laboratory finding that is not attributable to the underlying disease, disease progression, intercurrent illness or injury, or concomitant medications, occurring within the first 21 days of pelabresib treatment and meeting the protocol-specified criteria. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. For Japanese safety confirmation of the 125 mg QD dose, DLTs will be included in the decision-making process.

  Up to 21 days

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.

  Through study completion, an average of approximately 4 years

Secondary Outcomes (6)

• Plasma concentration time profiles of pelabresib

  Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.

• Area Under the plasma concentration-time Curve (AUC) of pelabresib

  Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.

• Maximum observed plasma Concentration (Cmax) of pelabresib

  Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.

• Time to Maximum observed plasma Concentration (Tmax) of pelabresib

  Cycle 1: Days 1/14 (0/Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose), Days 2/15 (0/Pre-dose (immediately before the next pelabresib administration)). 1 cycle = 21 days.

• Absolute change from baseline and percentage change from baseline in spleen volume over time (Week 24 and 48), as measured by MRI (or CT scan).

  Baseline, Week 24, Week 48

Study Arms (1)

Pelabresib + Ruxolitinib

EXPERIMENTAL

Eligible participants will receive pelabresib 125 mg once daily (QD) in combination with ruxolitinib at doses ranging from 5 to 25 mg twice daily (BID).

Drug: Pelabresib; Drug: Ruxolitinib

Interventions

Pelabresib DRUG

125 mg orally once daily (QD) on Days 1-14 of each 21-day cycle

Also known as: DAK539

Pelabresib + Ruxolitinib

Ruxolitinib DRUG

5-25 mg twice daily (BID)

Also known as: INC424

Pelabresib + 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), 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Kamogawa, Chiba, 296-8602, Japan

RECRUITING

Novartis Investigative Site

Sapporo, Hokkaido, 0030006, Japan

RECRUITING

Novartis Investigative Site

Kamakura, Kanagawa, 247-8533, Japan

RECRUITING

Novartis Investigative Site

Bunkyo Ku, Tokyo, 1138431, Japan

RECRUITING

Novartis Investigative Site

Chūō, Yamanashi, 409-3898, Japan

RECRUITING

Novartis Investigative Site

Kumamoto, 862-8655, Japan

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

+81337978748; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 14, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): November 16, 2026
• Study Completion (Estimated): December 18, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (6)