KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kartos Therapeutics, Inc.

Criteria

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 randomizatio

• 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)