To Assess the Safety and Tolerability of INCB000928 in Participants With Myelodysplastic Syndromes or Multiple Myeloma

Study Overview
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Brief Summary
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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 in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.

Official Title
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A Phase 1/2, Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma

Conditions
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Myelodysplastic Syndromes, Multiple Myeloma, Anemia

Intervention / Treatment
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* Drug: INCB000928


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agreement to avoid pregnancy or fathering children. Participants who are transfusion-dependent or present with symptomatic anemia For MDS participants: Ineligible to receive or have not responded to available therapies for anemia such as ESAs or lenalidomide. Not requiring cytoreductive therapy other than hydroxyurea. BM and peripheral blood myeloblast count < 10%. Histologically confirmed diagnosis of the MDS, CMML and unclassifiable MDS/MPN overlap syndromes. For MM participants: Histologically confirmed diagnosis of MM. After failure of available standard treatments such as alkylating agents, glucocorticoids, immunomodulatory drugs (lenalidomide,pomalidomide, or thalidomide), proteasome inhibitors (bortezomib or carfilzomib), and daratumumab. Exclusion Criteria: Any prior allogeneic stem cell transplantation or a candidate for such transplantation. Any major surgery within 28 days before the first dose of study drug. Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, or antibody or hypomethylating agent to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug. Undergoing treatment with another investigational medication or having been treated with an investigational medication within 28 days before the first dose of study drug. -Undergoing treatment with ESAs, granulocyte colony-stimulating factor or granulocyte/macrophage colony-stimulating factor, romiplostin, or eltrombopag at any time within 28 days before the first dose of study drug. Undergoing treatment with a strong or potent inhibitor or inducer of CYP3A4/5 within 28 days or 5 half-lives (whichever is longer) before the first dose of study drug or expected to receive such treatment during the study. History of clinically significant or uncontrolled cardiac disease. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically Meaningful. Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. Diagnosis of chronic liver disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB000928<br>INCB000928 will be administered in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia. | Drug: INCB000928<br>* INCB000928 will be administered once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-related adverse events | To determine the safety and tolerability of INCB000928 administered as monotherapy in participants with MDS or MM. | Approximately up to 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with anemia response (for TI patients at baseline) | Defined as an Hgb increase. | Approximately up to 7 months | 
| Duration of anemia response | Defined as the interval from the first onset of anemia response to the earliest date of loss of anemia response. | Approximately up to 7 months | 
| Proportion of participants with RBC-TI (for TD at baseline) | Defined as the absence of any RBC transfusion | Approximately up to 7 months | 
| Duration of RBC-TI period | Defined as duration of time for which participants are transfusion independent | Approximately up to 7 months | 
| Rate of RBC transfusion | Defined as the average number of RBC units | Through weeks 12 and 24 | 
| Increase in mean Hgb | Defined as the increase from baseline in the mean Hgb | Approximately up to 7 months | 
| MDS Participants only : Overall Response Rate | Defined as the proportion of participants with CR or PR | Approximately up to 7 months | 
| MDS Participants only : Progression Free Survival | Defined as the interval from the first dose of study drug until the first documented progression or death | Approximately up to 7 months | 
| MDS Participants only : Leukemia Free Survival | Defined as the interval from the first dose of study drug until the first documented leukemia transformation or death from any cause. | Approximately up to 7 months | 
| MM participants only : Overall Response Rate | Defined as the proportion of participants with stringent CR, CR, very good PR, and PR | Approximately up to 7 months | 
| MM Participants only : Progression Free Survival | Defined as the interval from the first dose of study drug until the first documented progression or death. | Approximately up to 7 months | 
| Cmax | Maximum plasma concentration of INCB000928 | C1D1 and C1D15 | 
| Tmax | Time to reach maximum (peak) plasma concentration of INCB000928 | C1D1 and C1D15 | 
| AUC0-t | Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. | C1D1 and C1D15 | 
| Hepcidin levels | Effect of INCB000928 on hepcidin levels | Approximately upto 7 months | 
| Iron Homeostasis | Effect of INCB000928 on iron homeostasis. | Approximately upto 7 months | 
| Erythropoiesis | Effect of INCB000928 on erythropoiesis. | Approximately upto 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, Multiple Myeloma, Anemia, LIMBER