Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

Kartos Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF); Post-Polycythemia Vera Myelofibrosis (Post-PV-MF); Primary Myelofibrosis (PMF)

Treatments: Drug: TL-895; Drug: KRT-232

Study type: Interventional

Funder types: Industry

Identifiers

NCT04878003

KRT-232-114

Details and patient eligibility

About

This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF)

The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.

Enrollment: 52 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
• High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS)
• ECOG of 0 or 1

Exclusion criteria

• Subjects who are positive for p53 mutation (Arm 1)
• Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)
• Prior treatment with any JAK inhibitor
• Prior splenectomy
• Splenic irradiation within 24 weeks prior to randomization
• Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell transplant
• History of major organ transplant
• Grade 2 or higher QTc prolongation
• Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Arm 1

Experimental group

Description:

KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles

Treatment:

Drug: KRT-232

Arm 2

Experimental group

Description:

TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles

Treatment:

Drug: TL-895