Title
KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
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
Phase
Phase 2Lead Sponsor
Kartos Therapeutics, Inc.Study Type
InterventionalStatus
RecruitingIntervention/Treatment
krt-232 ...Study Participants
385This 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.
KRT-232, administered by mouth
Best available therapy options include: hydroxyurea chemotherapy or supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).
KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
Best available therapy at the discretion of the investigator, on a 28-day cycle.
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)
