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KRT-232 treatment for myelofibrosis patients who have not responded to JAK inhibitors

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

Phase2; Phase3 Interventional Kartos Therapeutics, Inc. · NCT03662126

This study is testing a new treatment called KRT-232 for myelofibrosis patients who haven't had success with JAK inhibitors to see if it works better than the best current options.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment385 (estimated)
Ages18 Years and up
SexAll
SponsorKartos Therapeutics, Inc. Industry-sponsored
Locations191 sites (Birmingham, Alabama and 190 other locations)
Trial IDNCT03662126 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates KRT-232, a novel oral small molecule that inhibits MDM2, for patients with myelofibrosis who have relapsed or are refractory to JAK inhibitor treatments. The study consists of two phases: Phase 2 focuses on determining the optimal dose and schedule for KRT-232, while Phase 3 compares KRT-232 against the Best Available Therapy (BAT) in a randomized manner. Patients receiving BAT may switch to KRT-232 if their condition worsens or after six months. This approach aims to explore a new mechanism of action in treating myelofibrosis.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with primary myelofibrosis or post-polycythemia vera or post-essential thrombocythemia myelofibrosis who have failed prior JAK inhibitor therapy.

Not a fit: Patients who have undergone splenectomy or have a history of major hemorrhage or certain neurological events may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with myelofibrosis who have exhausted existing treatments.

How similar studies have performed: While this approach is novel in the context of myelofibrosis, other studies targeting MDM2 have shown promise in different cancer types.

Eligibility criteria

Show full inclusion / exclusion 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)

Where this trial is running

Birmingham, Alabama and 190 other locations

+141 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Primary MyelofibrosisPost-Polycythemia Vera MFPost-Essential Thrombocythemia MFnavtemadlin
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.