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: Recruiting
• Conditions: Myeloproliferative Neoplasms
• Intervention / Treatment: Drug: INCB160058; Drug: Standard disease-directed therapy

• Study Type: Interventional
• Enrollment (Estimated): 186
• 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

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • McGill University Jewish General Hospital
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • Hopital Maisonneuve-Rosemont, Montreal, Qc
• France
  • Paris, France, 75010
    • Recruiting
    • Hospital Saint Louis
  • Villejuif, France, 94805
    • Recruiting
    • Institut Gustave Roussy
• Germany
  • Aachen, Germany, D-52074
    • Recruiting
    • University Medical Center Rwth Aachen
  • Essen, Germany, 45147
    • Not yet recruiting
    • Universitätsklinikum Essen
  • Halle, Germany, 06120
    • Recruiting
    • Universitätsklinikum Halle (Saale)
• Italy
  • Bologna, Italy, 40138
    • Not yet recruiting
    • Aou Policlinico S. Orsola-Malpighi
  • Florence, Italy, 50134
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria Careggi (Aouc)
  • Milan, Italy, 20122
    • Not yet recruiting
    • Fondazione Irccs Ca Granda Ospedale Maggiore
• Norway
  • Bergen, Norway, N-5021
    • Recruiting
    • Haukeland University Hospital
  • Oslo, Norway, 00379
    • Recruiting
    • Oslo University Hospital
• Switzerland
  • Bern, Switzerland, 03010
    • Recruiting
    • Inselspital - Universitaetsspital Bern
  • Zurich, Switzerland, 08091
    • Recruiting
    • UniversitätsSpital Zürich
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Not yet recruiting
    • Guys and St Thomas NHS Foundation Trust
  • Oxford, United Kingdom, OX4 6LB
    • Not yet recruiting
    • Genesiscare Oxford
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • The University of Alabama at Birmingham
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center Kucc University of Kansas Clinical Research Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5008
      • Recruiting
      • University of Michigan
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10021
      • Recruiting
      • Cornell Medical Center
    • New York, New York, United States, 10065
      • Recruiting
      • Sloan Kettering Institute for Cancer Research
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Health System
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years

• MF:

  • Intermediate-1 or higher risk PMF, post-PV MF, or post-ET MF with evidence of minimum burden of disease based on splenomegaly, and for the monotherapy cohort, participants must have been previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment.
  • For the MF SubOpt R cohort: Therapeutic regimen prior to enrollment as defined in the protocol and unlikely to benefit from further monotherapy in the opinion of the investigator.
• PV: Confirmed diagnosis of PV and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment.
• ET: Confirmed diagnosis of high-risk ET as defined in the protocol and previously treated with at least 1 prior standard cytoreductive therapy and are resistant, refractory, intolerant to, or have lost response to treatment.
• 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.

Exclusion Criteria:

• Presence of a hematological malignancy requiring treatment, other than PMF, post-PV MF, post-ET MF, PV, or ET.
• 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.
• Acute or chronic HBV, active HCV or known HIV.
• Any prior MPN-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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation - with MF, PV or ET; 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), polycythemia vera (PV) or essential thrombocythemia (ET) will enroll in this group.	Drug: INCB160058; Oral; Tablet
Experimental: Part 2 Dose Expansion - with MF, PV or ET; INCB160058 will be administered at the RDE(s) identified during Part 1. Participants with MF, PV or ET will enroll in this group.	Drug: INCB160058; Oral; Tablet
Experimental: Part 1 Dose Escalation - with MF SubOpt R; INCB160058 will be administered at a protocol defined starting regimen and will allow for the evaluation of INCB160058 in combination with a standard disease-directed therapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF), suboptimal response to a standard disease-directed therapy (SubOpt R) will enroll in this group.	Drug: INCB160058; Oral; Tablet; Drug: Standard disease-directed therapy; A standard disease-directed therapy will be administered according to Prescribing Information/SmPC.
Experimental: Part 2 Dose Expansion - with MF SubOpt R; INCB160058 will be administered as an add-on therapy in combination with a standard disease-directed therapy at the RDE(s) identified during Part 1. Participants with myelofibrosis (MF), suboptimal response to a standard disease-directed therapy (SubOpt R) will enroll in this group.	Drug: INCB160058; Oral; Tablet; Drug: Standard disease-directed therapy; A standard disease-directed therapy will be administered according to Prescribing Information/SmPC.

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
For participants with MF: 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
For participants with MF: 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
For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV	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
For participants with ET: Response using revised IWG-MRT and ELN response criteria for ET	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
For all participants: 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
For all participants: Symptom improvement in TSS at Weeks 12 and 24 relative to baseline as measured by the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) TSS.	Defined as the proportion of participants who achieve a protocol defined reduction in Total Symptomatic Score (TSS) relative to baseline as measured by the MPN-SAF TSS.	Week 12 and Week 24
INCB160058 and a standard disease-directed therapy pharmacokinetic (PK) in Plasma	INCB160058 and the protocol defined standard disease-directed therapy concentration in plasma.	Up to Day 57

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2024
• Primary Completion (Estimated): October 9, 2028
• Study Completion (Estimated): October 9, 2028

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): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Myeloproliferative Neoplasms; Myelofibrosis; INCB160058
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: INCB160058-101; 2024-520353-21-00 (Registry Identifier: EU CT Number)

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