Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

An Open-Label, Multicenter, Phase 2 Study Assessing the Safety and Efficacy of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF)

The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.

Inclusion Criteria:

• Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
• High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS)
• ECOG of 0 or 1

Exclusion Criteria:

• Subjects who are positive for p53 mutation (Arm 1)
• Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)
• Prior treatment with any JAK inhibitor
• Prior splenectomy
• Splenic irradiation within 24 weeks prior to randomization
• Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell transplant
• History of major organ transplant
• Grade 2 or higher QTc prolongation
• Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization