INCB000928 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Anemia Due to Myeloproliferative Disorders

Incyte

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Anemia; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

Treatments: Drug: INCB000928; Drug: ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04455841

2023-503625-19-00 (Registry Identifier)

INCB 00928-104

2020-004029-21 (EudraCT Number)

Details and patient eligibility

About

This Phase 1/2, open-label, dose-finding study is intended to evaluate the safety and tolerability, PK, PD, and efficacy of INCB000928 administered as monotherapy or in combination with ruxolitinib in participants with MF who are transfusion-dependent or presenting with symptomatic anemia. This study will consist of 2 parts: dose escalation and expansion.

Enrollment: 84 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:

  1. Anemia: An Hgb value < 10 g/dL demonstrated during screening recorded on 3 separate occasions with at least 7 days between measurements (Note: RBC transfusion must be at least 2 weeks before the Hgb measurement during screening).
  2. Transfusion-dependent: Participant has received at least 4 units of RBC transfusions during the 28 days immediately preceding Cycle 1 Day 1 OR has received an average of at least 4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia. In addition, the most recent transfusion episode must have occurred in the 28 days before Cycle 1 Day 1.

• ECOG performance status score of the following:

  1. 0 or 1 for the dose-escalation stages.
  2. 0, 1, or 2 for the dose-expansion stage.

• Life expectancy is greater than 6 months

• Agreement to avoid pregnancy or fathering children.

• Ineligible to receive or have not responded to available therapies for anemia such as ESAs.

• For TGA:

• Participants previously treated with JAK inhibitors for at least 12 weeks.

• Participants with intermediate-2 or high DIPSS MF according to IWG-MRT criteria.

• For TGB:

• Participants must have been on a therapeutic and stable regimen of ruxolitinib for at least 12 consecutive weeks immediately preceding the first dose of study treatment.

• Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

• For TGC:

• Participants must be JAK inhibitor treatment naive (no prior treatment with any JAK inhibitor) and have an indication for initiation of ruxolitinib treatment.

• Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.

Exclusion criteria

• Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
• Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib for TGB only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• Laboratory Values outside of protocol defined range at screening.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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84 participants in 3 patient groups

Treatment Group A (TGA)

Experimental group

Description:

INCB000928 will be administered once daily (QD).

Treatment:

Drug: INCB000928

Treatment Group B (TGB)

Experimental group

Description:

INCB000928 will be administered in combination with ruxolitinib.

Treatment:

Drug: ruxolitinib

Drug: INCB000928

Treatment Group C (TGC)

Experimental group

Description:

INCB000928 will be administered in combination with ruxolitinib.

Treatment:

Drug: ruxolitinib

Drug: INCB000928