Recruiting
Phase 3

Navtemadlin & Ruxolitinib

Sponsor:

Kartos Therapeutics, Inc.

Code:

NCT06479135

Conditions

Myelofibrosis

Post-PV MF

Post-ET Myelofibrosis

Primary Myelofibrosis

MF

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Navtemadlin

Navtemadlin placebo

Ruxolitinib

Study Details

Brief summary:

This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone.

Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.

Conditions

Myelofibrosis

Post-PV MF

Post-ET Myelofibrosis

Primary Myelofibrosis

MF

Study ID

NCT06479135

Start date

Jun 3, 2024

Status verified date

Oct, 2024

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1

Navtemadlin administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.

active comparator: Arm 2

Navtemadlin placebo administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.

Interventions

Navtemadlin

Navtemadlin is an investigational MDM2 inhibitor

Navtemadlin placebo

Navtemadlin placebo

Ruxolitinib

Ruxolitinib is a janus kinase 1/2 inhibitor

Primary outcome measure

  • To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2 [ Time Frame: 24 weeks ]
  • To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2 [ Time Frame: 24 weeks ]

Central Contacts and Locations

Central contacts

John Mei

650-542-0136jmei@kartosthera.com

Locations

UAB Hospital

Recruiting

Birmingham, Alabama, United States, 35233

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

Mayo Clinic - Phoenix

Recruiting

Phoenix, Arizona, United States, 85054

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92037

UCLA Hematology/Oncology Clinic - Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Scripps Health, Prebys Cancer Center

Recruiting

San Diego, California, United States, 92103

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Recruiting

Torrance, California, United States, 90502

Rocky Mountain Cancer Centers - Aurora

Recruiting

Aurora, Colorado, United States, 80012

Medical Oncology Hematology Consultants, PA

Recruiting

Newark, Delaware, United States, 19713

MedStar Georgetown University Hospital, Lombardi Comprehensive Cancer Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

Mayo Clinic - Jacksonville

Recruiting

Jacksonville, Florida, United States, 32224

University of Miami

Recruiting

Miami, Florida, United States, 33136

AdventHealth Cancer Institute

Recruiting

Orlando, Florida, United States, 32803

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Mission Cancer + Blood

Recruiting

Des Moines, Iowa, United States, 50314

University of Kansas Cancer Center - Westwood

Recruiting

Westwood, Kansas, United States, 66205

Norton Cancer Institute

Recruiting

Louisville, Kentucky, United States, 40207

Mary Bird Perkins Cancer Center

Recruiting

Baton Rouge, Louisiana, United States, 70809

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Recruiting

Baltimore, Maryland, United States, 21231

The Center for Cancer and Blood Disorders

Recruiting

Bethesda, Maryland, United States, 20817

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

University of Michigan Hospital

Recruiting

Ann Arbor, Michigan, United States, 48109

Henry Ford Cancer Institute - Brigitte Harris Cancer Pavilion

Recruiting

Detroit, Michigan, United States, 48202

Nebraska Hematology - Oncology, P.C.

Recruiting

Lincoln, Nebraska, United States, 68506

Mohtaseb Cancer Center and Blood Disorders

Recruiting

Henderson, Nevada, United States, 86442

Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601

Brookdale University Hospital and Medical Center

Recruiting

Brooklyn, New York, United States, 11212

Cayuga Cancer Center

Recruiting

Ithaca, New York, United States, 14850

Northwell Health, R.J. Zuckerberg Cancer Center

Recruiting

Lake Success, New York, United States, 11042

ICAHN School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029-6574

Montefiore Einstein Comprehensive Cancer Center

Recruiting

The Bronx, New York, United States, 10467

Medical University of South Carolina (MUSC)

Recruiting

Charleston, North Carolina, United States, 29425-8900

Atrium Health Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Regional Medical Oncology Center

Recruiting

Wilson, North Carolina, United States, 27893

Atrium Health Wake Forest Baptist

Recruiting

Winston-Salem, North Carolina, United States, 27157

Gabrail Cancer Center

Recruiting

Canton, Ohio, United States, 44718

University of Cincinnati Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Cleveland Clinic Cancer Center at Fairview Hospital

Recruiting

Cleveland, Ohio, United States, 44111

Cleveland Clinic

Recruiting

Cleveland, Ohio, United States, 44195

Independence Family Health Center - Cleveland Clinic

Recruiting

Independence, Ohio, United States, 44131

Hillcrest Hospital - Cleveland Clinic

Recruiting

Mayfield Heights, Ohio, United States, 44124

Willamette Valley Cancer Institute and Research Center

Recruiting

Eugene, Oregon, United States, 97401

Abramson Cancer Center of the University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

West Penn Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15224

Tennessee Oncology

Recruiting

Chattanooga, Tennessee, United States, 37404

Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

UT - SouthWestern

Recruiting

Dallas, Texas, United States, 75390

U.T. MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

The University of Texas Health Science Center at San Antonio

Recruiting

San Antonio, Texas, United States, 78229

University of Utah, Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112

Virginia Cancer Institute

Recruiting

Richmond, Virginia, United States, 23229

VCU Medical Center

Recruiting

Richmond, Virginia, United States, 23298

Virginia Oncology Associates - Virginia Beach

Recruiting

Virginia Beach, Virginia, United States, 23456

Fred Hutchinson Cancer Centre

Recruiting

Seattle, Washington, United States, 98109

Northwest Medical Specialties, PLLC - Tacoma

Recruiting

Tacoma, Washington, United States, 98405

Sheboygan Cancer & Blood Specialists

Recruiting

Sheboygan, Wisconsin, United States, 53081

More Information

Sponsor

Kartos Therapeutics, Inc.

Last update posted

Sep 25, 2025

Last verified

Oct, 2024

Keywords

  • Navtemadlin
  • KRT-232
  • Ruxolitinib
  • POIESIS
  • TP53
  • Suboptimal response
  • Sub-optimal response

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Kartos Therapeutics, Inc. on 2025-09-25.