An Open-Label, Phase 2a/2b Study of KRT-232 in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post-ET-MF) Who Have Failed a JAK Inhibitor
Brief SummaryThis study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study is a global, open-label Phase 2 study to determine the efficacy and safety of KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF who have failed previous treatment with JAK inhibitor (Part A), or Ruxolitinib (Part B). In Part A of the study, patients will be randomly assigned to 2 different doses and 3 different dosing schedules of KRT-232. In Part B of the study, patients will be treated at the recommended dose and schedule from Part A.
Inclusion and Exclusion Criteria
- Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
- High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
- Failure of prior treatment with JAK inhibitor (Part A) or ruxolitinib (Part B)
- ECOG ≤ 2
- Prior splenectomy
- Splenic irradiation within 3 months prior to the first dose of KRT-232
- Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232
- Prior MDM2 inhibitor therapy or p53-directed therapy
- Prior treatment with HDAC or BCL-2 inhibitors
- Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.