This Phase II trial is evaluating how safe and effective a new drug (KER-050) is alone, and in combination with targeted therapy (ruxolitinib) in people with myelofibrosisA Phase 2 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of KER-050 as Monotherapy or in Combination With Ruxolitinib in Participants With Myelofibrosis

Exclusion

• Presence of the following cardiac conditions:

  1. New York Heart Association Class 3 or 4 heart failure
  2. QTcF >500 msec on the screening or C1D1 electrocardiogram (ECG)
  3. Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded)
  4. Acute myocardial infarction or unstable angina pectoris <6 months prior to C1D1
• History of stroke, deep venous thrombosis, or arterial embolism within 6 months prior to C1D1.
• Any malignancy other than PMF, post-ET MF, or post-PV MF that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or surgery, within 1 year prior to C1D1. In-situ cancers, squamous cell, and basal cell carcinomas which have been fully excised, and monoclonal gammopathy of unclear significance are allowed at the discretion of the Investigator.
• History of solid organ or hematological transplantation.
• Presence of uncontrolled hypertension, defined as systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg despite adequate treatment.
• Diagnosis of hemolytic anemia, active bleeding, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia.
• CTCAE Grade ≥2 bleeding events within the 3 months prior to C1D1.
• Bone marrow blast percentage >2%. Participants with blast % between 2-5% are allowed if at least 2 bone marrows >6 months apart demonstrate stability of blast percentage, these participants must be reviewed with the Medical Monitor prior to study entry.
• Prior treatment with luspatercept, sotatercept, or other commercially available or investigational TGF-β inhibitors (all Arms)

• Treatment within 28 days prior to C1D1 with:

  1. Erythropoiesis stimulating agent (ESA)
  2. Granulocyte colony-stimulating factor (G-CSF)
  3. Granulocyte-macrophage colony-stimulating factor (GM-CSF)
  4. Thrombopoietin agonists (TPO)
  5. Immunomodulator imide drugs (IMiDs; e.g., thalidomide, pomalidomide, lenalidomide)
  6. Interferon