OUR CLINICAL RESEARCH
Navtemadlin Development
| Myelofibrosis Study | Phase 1 | Phase 2 | Phase 3 |
|---|---|---|---|
 Navtemadlin + ruxolitinib Suboptimal response to ruxolitinib |
Recruiting |
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|
KRT-232-109 Navtemadlin + ruxolitinib Suboptimal response to ruxolitinib |
Active, Not Recruiting |
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 Navtemadlin JAKi relapse/refactory |
Active, Not Recruiting |
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Targeting MDM2 Restores Apoptosis in CD34+ MF Cells
A clinically significant hallmark of MF is splenomegaly, or enlarged spleen, which becomes a home for CD34+ MF cells. This is enabled by overexpression of MDM2, which inhibits p53, leading to increased survival and proliferation. Navtemadlin is a selective, oral MDM2 inhibitor designed to restore the function of p53, a key tumor suppressor protein, thereby promoting cell cycle arrest or apoptosis in CD34+ MF cells with wild-type TP53.
Within the CD34+ MF cell, inhibition of p53 by MDM2 also suppresses pro-apoptotic Bcl-2 proteins on the mitochondria, supporting cell survival. When navtemadlin blocks MDM2, p53 can activate Bcl-2 proteins, which leads to mitochondrial pore formation, release of cytochrome C, activation of Caspase 9, and ultimately, death of CD34+ MF cells.
KARTOS-SPONSORED TRIALS
Myelofibrosis (MF) – POIESIS
Status: Recruiting
ClinicalTrials.gov: NCT06479135
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
Myelofibrosis (MF)
Status: Active, Not Recruiting
ClinicalTrials.gov: NCT04485260
An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of Navtemadlin (KRT-232) Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib.
Myelofibrosis (MF) – BOREAS
Status: Active, Not Recruiting
ClinicalTrials.gov: NCT03662126
Navtemadlin (KRT-232) Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment (BOREAS)
EXPANDED ACCESS PROGRAM
Expanded access, also known as “compassionate use,” refers to the use of an investigational agent outside of a clinical trial. This is a U.S. Food and Drug Administration (FDA) initiative that allows patients with serious illnesses, who have exhausted all other treatment options, the opportunity to access investigational agents that are not yet approved. It is important to remember that the safety and efficacy of these agents have not yet been established. Physicians and patients should discuss all possible benefits and risks before seeking expanded access to an investigational agent.
Kartos Therapeutics will evaluate each request for expanded access to navtemadlin. All requests must be submitted to eap@kartosthera.com by a licensed healthcare professional. We will review the request promptly and respond within 48 hours.
For more information on the FDA Expanded Access program, please see the FDA website on Expanded Access, and/or talk to your healthcare provider.