Overview
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.
Eligibility
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