A Study to Evaluate the Safety, Tolerability of INCB160058 in Participants With Myeloproliferative Neoplasms

A Phase 1, Open-Label, Multicenter Study of INCB160058 in Participants With Myeloproliferative Neoplasms

This study is being conducted to assess the Safety, Tolerability, and Pharmacokinetics of INCB160058 in Participants With Myeloproliferative Neoplasms.

Study Overview

• Status: Not yet recruiting
• Conditions: Myeloproliferative Neoplasms
• Intervention / Treatment: Drug: INCB160058

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (US); Phone Number: 1.855.463.3463; Email: medinfo@incyte.com
• Study Contact Backup: Name: Incyte Corporation Call Center (ex-US); Phone Number: +800 00027423; Email: eumedinfo@incyte.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Participants with intermediate-1 or higher risk PMF, post-PV, of post-ET MF, histologically confirmed
• Evidence of minimum burden of disease based on symptoms and/or splenomegaly
• Life expectancy > 6 months
• Willingness to undergo a pretreatment and regular on-study bone marrow biopsies and aspirations (as appropriate to disease)
• Existing documentation of JAK2V617F mutation from a qualified local laboratory
• Previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment

Exclusion Criteria:

• Presence of a hematological malignancy requiring treatment, other than PMF, post-PV MF, or post-ET MF
• Prior history of major bleeding or thrombosis within the 3 months prior to study enrollment
• Participants with abnormal hematologic, hepatic, or renal function based on laboratory evaluation
• Has undergone prior allogenic or autologous stem-cell transplantation or allogenic stem-cell transplantation is planned
• Active invasive malignancy
• Significant concurrent, uncontrolled medical condition
• Active HBV/HCV or known HIV
• Any prior MF-directed therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment
• Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at any time within 4 weeks before the first dose of study treatment

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation - with MF; INCB160058 will be administered at a protocol defined starting regimen to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) will enroll in this group.	Drug: INCB160058; Oral; Tablet
Experimental: Part 2 Dose Expansion - with MF; INCB160058 will be administered at the RDE(s) identified during Part 1. Participants with MF will enroll in this group.	Drug: INCB160058; Oral; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Dose Limiting Toxicities (DLTs)	Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.	Up to 28 days
Number of participants with TEAEs leading to dose modification or discontinuation	Number of participants with TEAEs leading to dose modification or discontinuation.	Up to 2 years and 30 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to 2 years and 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
INCB160058 pharmacokinetic (PK) in Plasma	INCB160058 concentration in plasma.	Up to Day 57
Response using the revised IWG-MRT and ELN response criteria for MF	Defined as the percentage of participants with Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria.	Week 12 and 24 and then every 24 weeks up to 2 years
Percentage of participants achieving spleen volume reduction as defined in the protocol	Defined as percentage of participants with a protocol defined Spleen Volume Reduction.	Week 12 and Week 24
Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)	Defined as the percentage of participants achieving ≥ 50% reduction from baseline of TSS.	Week 24
Participants with MF with symptomatic anemia: Anemia Response	For non transfusion-dependent (TD) participants: A hemoglobin increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.	Up to 2 years and 30 days

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Incyte Medical, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): June 14, 2024
• Primary Completion (Estimated): June 6, 2027
• Study Completion (Estimated): September 4, 2027

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Myeloproliferative Neoplasms; Myelofibrosis; INCB160058
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Neoplasms; Myeloproliferative Disorders
• Other Study ID Numbers: INCB160058-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No