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Adding navtemadlin to ruxolitinib for myelofibrosis patients with poor response

A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

PHASE3 · Kartos Therapeutics, Inc. · NCT06479135

This study is testing if adding a new drug called navtemadlin to ruxolitinib can help myelofibrosis patients who aren't doing well on ruxolitinib alone.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorKartos Therapeutics, Inc. (industry)
Drugs / interventionsRuxolitinib
Locations215 sites (Birmingham, Alabama and 214 other locations)
Trial IDNCT06479135 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of adding navtemadlin to ruxolitinib treatment for patients with myelofibrosis who have not responded adequately to ruxolitinib alone. Initially, participants will receive ruxolitinib during a run-in period, and those showing a suboptimal response will be randomly assigned to receive either navtemadlin or a placebo alongside their ongoing ruxolitinib treatment. The study is designed to be blinded, ensuring that neither the participants nor the healthcare providers know which treatment is being administered. This approach aims to determine if the combination therapy can provide better clinical outcomes than ruxolitinib alone.

Who should consider this trial

Good fit: Ideal candidates include patients with primary myelofibrosis or post-PV/post-ET myelofibrosis who are JAK-inhibitor naive and have a suboptimal response to ruxolitinib.

Not a fit: Patients who have previously undergone splenectomy or have high blast counts in their blood or bone marrow may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for myelofibrosis patients who do not respond well to ruxolitinib alone.

How similar studies have performed: Other studies have explored combination therapies in myelofibrosis, but the specific combination of navtemadlin with ruxolitinib is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria for Ruxolitinib Alone Period:

* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
* High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* JAK-inhibitor treatment naive

Exclusion Criteria for Ruxolitinib Alone Period:

* Prior Splenectomy
* Splenic irradiation within 3 months prior to the first dose
* Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
* Eligible for Bone Marrow Transplant
* Peripheral blood or bone marrow blast count ≥ 10 percent

Inclusion Criteria for Randomized Period:

* PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
* ECOG performance status of 0 to 2
* Treatment with a stable dose of ruxolitinib
* Suboptimal response to run-in ruxolitinib treatment

Exclusion Criteria for Randomized Period:

* Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10\^9/L
* Peripheral blood or bone marrow blast count ≥ 10 percent

Where this trial is running

Birmingham, Alabama and 214 other locations

+165 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 →

Conditions: Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis, MF, Navtemadlin, KRT-232, Ruxolitinib

Last reviewed 2026-05-15 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.