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KRT-232 and TL-895 for treating myelofibrosis

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis.

Phase1; Phase2 Interventional Kartos Therapeutics, Inc. · NCT04640532

This study is testing a new combination of two drugs, KRT-232 and TL-895, to see if they can help people with myelofibrosis who haven't responded to other treatments or can't take certain medications.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment116 (estimated)
Ages18 Years and up
SexAll
SponsorKartos Therapeutics, Inc. Industry-sponsored
Locations37 sites (Birmingham, Alabama and 36 other locations)
Trial IDNCT04640532 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of KRT-232 in combination with TL-895 for patients with relapsed or refractory myelofibrosis, as well as KRT-232 for those intolerant to JAK inhibitors. The trial consists of three cohorts, with the first two focusing on dose escalation to determine the maximum tolerated dose of TL-895 when combined with KRT-232. The third cohort will expand based on the response rates observed in the initial stage. Safety data will be continuously reviewed to guide dose adjustments and treatment decisions.

Who should consider this trial

Good fit: Ideal candidates include patients with confirmed primary myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis who have relapsed after JAK inhibitor treatment or are intolerant to such therapies.

Not a fit: Patients who have previously received MDM2 inhibitors or other specified therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat forms of myelofibrosis.

How similar studies have performed: While this approach is novel in its specific combination, similar studies have shown promise in treating myelofibrosis with targeted therapies.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Confirmed diagnosis of primary MF, post-PV MF, or post-ET MF, (WHO 2016)
* ECOG ≤ 2
* Cohort 1 and Cohort 2: R/R following JAK inhibitor treatment
* Cohort 3: patients who are intolerant to JAK inhibitor treatment

Exclusion Criteria:

* Prior treatment with MDM2 inhibitors or p53-directed therapies
* Prior treatment with a BCR-ABL, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR), bromodomain and extraterminal domain (BET), histone deacetylase (HDAC), or spleen tyrosine kinase (Syk) inhibitor
* Prior splenectomy
* Splenic irradiation within 3 months prior to the first dose of study treatment
* Clinically significant thrombosis within 3 months of screening
* Grade 2 or higher QTc prolongation

Where this trial is running

Birmingham, Alabama and 36 other locations

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 MyelofibrosisPost-PV MFPost-ET MyelofibrosisPrimary MyelofibrosisRelapsed/Refractory MyelofibrosisJanus associated Kinase Inhibitor-Intolerant MyelofibrosisMDM2navtemadlin
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.