KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment

Kartos Therapeutics, Inc.385 enrolled

Overview

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 a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF. This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

385

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 * ECOG ≤ 2 Exclusion Criteria: * Prior splenectomy * Splenic irradiation within 3 months prior to randomization * History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization * History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization * Prior MDM2 inhibitor therapy or p53-directed therapy * Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant * History of major organ transplant * Grade 2 or higher QTc prolongation (\> 480 milliseconds per NCI-CTCAE criteria, version 5.0)

Locations (191)

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama, United States

ACTIVE_NOT_RECRUITING

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States

ACTIVE_NOT_RECRUITING

Stanford Cancer Center - Palo Alto

Stanford, California, United States

ACTIVE_NOT_RECRUITING

Innovative Clinical Research Institute

Whittier, California, United States

Outcomes

Primary Outcomes

(Part A Only) Spleen Volume Reduction (SVR)

The proportion of subjects achieving a ≥ 35% spleen volume reduction (SVR) from Baseline to Week 24, as assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scan

Time frame: 24 weeks

(Part B Only) Spleen Volume Reduction (SVR)

The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan (central review)

Time frame: 24 Weeks

Secondary Outcomes

(Part A only) Improvement in Total Symptom Score (TSS)

The proportion of subjects who have at least a 50% reduction from Baseline to Week 24 and Week 48 in the total symptom score as measured by the modified MPN-SAF v2.0

Time frame: 48 weeks

(Part B only) Improvement of Total Symptom Score (TSS)

The proportion of subjects who have at least a 50% reduction from Baseline to Week 24 in the total symptom score as measured by the MF-SAF v4.0

Time frame: 24 Weeks

(Part B only) Overall Survival (OS)

Time from randomization to death from any cause

Time frame: 48 months

(Part B only) Progression free survival (PFS)

Time from randomization to either first occurrence of disease progression or death due to any cause

Time frame: 48 months

(Part B Only) Overall Spleen Volume Reduction (SVR)

The proportion of subjects in each arm achieving SVR of ≥ 35% at any time by MRI/CT scan (central review)

Time frame: 48 months

(Part B Only) Spleen Response Duration

Time from initial SVR of ≥ 35% by MRI/CT (central review) until the first occurrence of disease progression

Time frame: 48 months

(Part B Only) Rate of conversion from RBC transfusion dependent to independent

The proportion of subjects who have RBC transfusion independence at week 24

Time frame: 24 weeks

KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment

Overview

Conditions

Interventions

Eligibility

Locations (191)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts