KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera

Kartos Therapeutics

Status and phase: Unknown; Phase 2

Conditions: Polycythemia Vera

Treatments: Drug: KRT-232; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03669965

KRT-232-102

Details and patient eligibility

About

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with phlebotomy-dependent polycythemia vera (PV). Inhibition of MDM2 in PV is a new mechanism of action in PV. In Part A, patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon. In Part B, patients must be resistant or intolerant to hydroxyurea.

This study is a global, open-label Phase 2a/2b study to determine the efficacy and safety of KRT-232. In Part A of the study, patients will be randomly assigned to 5 arms with 2 different doses and 3 different dosing schedules of KRT 232. In Part B of the study, patients will be randomized either to treatment with KRT-232 administered at the recommended dose and schedule from Part A or to treatment with ruxolitinib.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of PV (WHO 2016)
• ECOG ≤ 2
• Part A: patients with and without splenomegaly are eligible
• Part A: patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon
• Part B: only patients with splenomegaly are eligible
• Part B: patients must be resistant or intolerant to hydroxyurea

Exclusion criteria

• Diagnosis of post-PV myelofibrosis (IWG-MRT)
• Prior treatment with MDM2 inhibitors, p53-directed therapies, HDAC, BCL 2 inhibitors
• Splenic irradiation within 3 months prior to the first dose of study treatment
• Clinically significant thrombosis within 3 months of screening
• Grade 2 or higher QTc prolongation
• Part B: prior treatment with a JAK inhibitor

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

20 participants in 7 patient groups

Part A Arm 1

Experimental group

Description:

KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

Treatment:

Drug: KRT-232

Part A Arm 2

Experimental group

Description:

KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

Treatment:

Drug: KRT-232

Part A Arm 3

Experimental group

Description:

KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Treatment:

Drug: KRT-232

Part B KRT-232 Arm

Experimental group

Description:

Recommended KRT-232 dose and schedule from Part A

Treatment:

Drug: KRT-232

Part B Ruxolitinib Arm

Active Comparator group

Description:

Ruxolitinib per approved prescribing label

Treatment:

Drug: Ruxolitinib

Part A Arm 4b

Experimental group

Description:

KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)

Treatment:

Drug: KRT-232

Part A Arm 2b

Experimental group

Description:

KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Treatment:

Drug: KRT-232