A Phase 2, Open-Label, Ascending Dose Study of KER-050 for the Treatment of Anemia in Patients With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)
The main aim of this study is to learn how safe elritercept is and how well adults with anemia associated with lower-risk MDS tolerate treatment with different doses of elritercept. Other aims are to learn how safe elritercept is by looking at how many participants have MDS that worsens during the study and learn about the effects of elritercept on anemia linked to MDS. The study will also look to learn how elritercept affects the production of healthy RBCs.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local study participant privacy regulations.
• Male or female ≥ 18 years of age, at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
• Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception.
• In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits).
⁃ Part 1 Inclusion Criteria
⁃ Participants are eligible to be included in Part 1 of the study only if all the following criteria apply:
• Diagnosis of MDS according to WHO classification that meets International Prognostic Scoring System-Revised (IPSS-R) classification of very low, low, or intermediate risk disease.
• Less than (\<)5percent (%) blasts in bone marrow during the Pretreatment Period.
• Peripheral blood white blood cell (WBC) count \<13,000/microliter (μL) during the Pretreatment Period.
• Anemia defined as:
∙ In non-transfused participants, having received no RBC transfusions within 8 weeks, Hgb concentration ≤ 10.0 g/dL during the Pretreatment Period OR
‣ In LTB participants, having received 1 to 3 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period.
∙ OR
‣ In HTB participants, having received ≥ 4 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period.
⁃ Part 1 Extension - Abbreviated Inclusion Criteria
⁃ Participants from Part 1 are eligible to be included in Part 1 Extension of the study only if all the following criteria apply:
• Previously completed 4 cycles of elritercept in Part 1 with no dose-limiting toxicities (DLTs).
• Participant has the potential to benefit from administration of elritercept, in the opinion of the Investigator.
• \< 5% blasts in bone marrow.
• Peripheral WBC count \< 13,000/μL during the 28 days prior to cycle 5 day 1 (C5D1).
⁃ Part 2 Inclusion Criteria
⁃ Participants are eligible to be included in Part 2 of the study only if all the following criteria apply:
• Cohort A:
‣ Diagnosis of MDS according to WHO classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
⁃ ring sideroblast (RS)-positive as defined by WHO 2016 criteria.
⁃ Requiring at least 2 units of RBC transfusions in the preceding 8 weeks before cycle 1 day 1 (C1D1).
• Cohort B:
‣ Diagnosis of MDS according to WHO classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
⁃ Non-RS as defined by WHO 2016 criteria.
⁃ Requiring at least 2 units of RBC transfusions in the 8 weeks before C1D1.
• Cohort C:
‣ Diagnosis of MDS according to WHO classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
⁃ Has anemia, defined by Hgb ≤ 10 g/dL during the Pretreatment Period, and received no RBC transfusion in the 8 weeks before C1D1.
• Cohort D:
‣ Diagnosis of CMML according to WHO classification.
⁃ Has anemia, defined by Hgb ≤ 10 g/dL during the Pretreatment Period, and received no RBC transfusion in the 8 weeks before C1D1.
⁃ OR
⁃ Received at least 2 units of RBC transfusions for anemia in the 8 weeks before C1D1.
• Cohort E:
‣ Diagnosis of MDS according to WHO classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
⁃ Requiring ≥ 2 units of RBC transfusions in the preceding 8 weeks before C1D1.
⁃ Receipt of ≥ 20 units of RBC in transfusion over the participant's lifetime.
⁃ Serum ferritin \> 1000 nanograms per milliliter (ng/mL) on ≥ 2 assessments in the preceding 8 weeks before C1D1.
⁃ Treated with stable dose of iron chelation therapy for ≥ 8 weeks prior to C1D1.
• Cohort F:
‣ Diagnosis of MDS according to WHO classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
⁃ Requiring ≥ 2 units of RBC transfusions in the preceding 8 weeks before C1D1.
⁃ Receipt of ≥ 20 units of RBC in transfusion over the participant's lifetime.
⁃ Serum ferritin \> 1000 ng/mL on ≥ 2 assessments in the preceding 8 weeks before C1D1.
⁃ Not treated with iron chelation therapy in the preceding 8 weeks before C1D1 and not eligible to initiate iron chelation therapy in the opinion of the Investigator and in accordance with local treatment guidelines for initiation of iron chelation therapy.
• Cohort G:
‣ Diagnosis of MDS according to WHO classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
⁃ RS-positive as defined by WHO 2016 criteria OR non-RS as defined by WHO 2016 criteria.
⁃ Relapsed, refractory, or intolerant to frontline luspatercept treatment and have not received an interceding therapy (for example, erythropoiesis-stimulating agent \[ESA\])
• Relapsed is defined as documentation of response to luspatercept therapy and subsequent development of a need for transfusion(s).
∙ Refractory is defined as documentation of no response with luspatercept ≥ 1 mg/kg administered for ≥ 12 weeks duration.
∙ Intolerant is defined as documentation of discontinuation of luspatercept therapy due to intolerance or an AE at any time after introduction.
⁃ Requiring ≥ 2 units of RBC transfusions over 8 weeks prior to C1D1.
⁃ Erythropoietin (EPO) \< 500 international units per liter (U/L) at Baseline.
⁃ Last dose of luspatercept is ≥ 3 weeks and \< 12 months from C1D1.
• \< 5% blasts in bone marrow assessed by bone marrow aspirate during the Pretreatment Period.