KRT-232 in Subjects With PMF, Post-PV MF, or Post-ET MF Who Have Failed a JAK Inhibitor

Status:	Recruiting
Conditions:	Hematology, Hematology
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	18 - Any
Updated:	4/3/2019
Start Date:	January 15, 2019
End Date:	February 28, 2023
Contact:	John Mei
Email:	jmei@kartosthera.com
Phone:	650-542-0136

An Open-Label, Phase 2a/2b 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 Have Failed a JAK Inhibitor

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the
treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with JAK
inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.

This study is a global, open-label Phase 2 study to determine the efficacy and safety of
KRT-232 in patients with primary MF, post-polycythemia vera MF, or post-essential
thrombocythemia MF who have failed previous treatment with JAK inhibitor (Part A), or
Ruxolitinib (Part B). In Part A of the study, patients will be randomly assigned to 2
different doses and 2 different dosing schedules of KRT-232. In Part B of the study, patients
will be treated at the recommended dose and schedule from Part A.

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 (Part A) or ruxolitinib (Part B)

- ECOG ≤ 2

Exclusion Criteria:

- Prior splenectomy

- Splenic irradiation within 3 months prior to the first dose of KRT-232

- Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232

- Prior MDM2 inhibitor therapy or p53-directed therapy

- Prior treatment with HDAC or BCL-2 inhibitors

- Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version
5.0)

We found this trial at

sites

Health Partners Institute

640 Jackson Street
Saint Paul, Minnesota 55101

Phone: 651-254-3391

from

Saint Paul, MN