A Phase 2/3 Randomized, Controlled, Open-Label 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 Are Relapsed or Refractory to Janus Kinase (JAK) Inhibitor Treatment

Description

This 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 a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.

Trial Eligibility

Inclusion 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 * ECOG ≤ 2 Exclusion Criteria: * Prior splenectomy * Splenic irradiation within 3 months prior to randomization * History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization * History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization * Prior MDM2 inhibitor therapy or p53-directed therapy * Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant * History of major organ transplant * Grade 2 or higher QTc prolongation (\> 480 milliseconds per NCI-CTCAE criteria, version 5.0)

Study Info

Interventions

Locations Recruiting

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