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

Sponsor: Kartos Therapeutics, Inc.

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT03662126

Patient View

This clinical trial assesses KRT-232, an oral MDM2 inhibitor, for myelofibrosis patients unresponsive to JAK inhibitors. It includes a Phase 2 dose-finding study and a Phase 3 comparison with Best Available Therapy (BAT). Eligible participants have specific MF diagnoses and prior JAK inhibitor failure. Exclusions include prior MDM2 therapy and recent major hemorrhages.

Patient Parameters

Program Overview

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.

Eligibility 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 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)

Get This Program In Your Inbox

You can sign up and apply your patients for this program.