KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment (BOREAS)

Prior treatment

• Part B: Prior splenectomy
• Part B: Splenic irradiation within 12 weeks of randomization
• Part B: Prior allogeneic stem-cell transplantation or plans for allogeneic stem cell transplantation
• Part B: Prior MDM2 inhibitor therapy or p53-directed therapy
• Part B: JAK-, PI3k-, SYK-, BTK-, BET- or MTOR inhibitor treatment within 28 days prior to the Screening MRI/CT scan
• Part A: Prior splenectomy
• Part B: History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
• Part B: History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
• Part A: Splenic irradiation within 3 months prior to randomization
• Part A: History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
• Part A: History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
• Part A: Prior MDM2 inhibitor therapy or p53-directed therapy
• Part A: Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant

Other illness

• Part B: History of major organ transplant
• Part A: History of major organ transplant

Lab values

• Part A: Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
• Part B: Grade 2 or higher QTc prolongation (>480 milliseconds per NCI- CTCAE criteria, version 5.0)

Other

• Part A: Subjects who are positive for P53 mutations

• Part A: Adults ≥18 years of age
• Part B: Failure of prior treatment with JAK inhibitor
• Part B: ECOG ≤ 2
• Part A: Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
• Part A: High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
• Part A: Failure of prior treatment with JAK inhibitor
• Part A: ECOG ≤ 2
• Part B: Adults >18 years of age
• Part B: Confirmed diagnosis of PMF, post PV-MF, or post-ET-MF (WHO)
• Part B: High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
• Part B: Subjects with p53WT MF by central laboratory testing