A Study to Evaluate the Safety, Tolerability of INCB160058 in Participants With Myeloproliferative Neoplasms
- Registration Number
- NCT06313593
- Lead Sponsor
- Incyte Corporation
- Brief Summary
This study is being conducted to assess the Safety, Tolerability, and Pharmacokinetics of INCB160058 in Participants With Myeloproliferative Neoplasms.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 144
- 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 previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment.
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Dose Escalation - with MF, PV or ET INCB160058 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. Part 2 Dose Expansion - with MF, PV or ET INCB160058 INCB160058 will be administered at the RDE(s) identified during Part 1. Participants with MF, PV or ET will enroll in this group.
- Primary Outcome Measures
Name Time Method Number of participants with TEAEs leading to dose modification or discontinuation Up to 2 years and 30 days Number of participants with TEAEs leading to dose modification or discontinuation.
Number of participants with Treatment-emergent Adverse Events (TEAEs) Up to 2 years and 30 days Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
Number of participants with Dose Limiting Toxicities (DLTs) Up to 28 days Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
- Secondary Outcome Measures
Name Time Method INCB160058 pharmacokinetic (PK) in Plasma Up to Day 57 INCB160058 concentration in plasma.
For participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF Week 12 and 24 and then every 24 weeks up to 2 years 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.
For participants with MF: Percentage of participants achieving spleen volume reduction as defined in the protocol Week 12 and Week 24 Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV Week 12 and 24 and then every 24 weeks up to 2 years 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.
For participants with ET: Response using revised IWG-MRT and ELN response criteria for ET Week 12 and 24 and then every 24 weeks up to 2 years 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.
For all participants: Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS) Week 24 Defined as the percentage of participants achieving ≥ 50% reduction from baseline of TSS.
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. Week 12 and Week 24 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.
Trial Locations
- Locations (10)
University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
Stanford University
🇺🇸Palo Alto, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
The University of Kansas Cancer Center Kucc University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Icahn School of Medicine At Mount Sinai
🇺🇸New York, New York, United States
Sloan Kettering Institute For Cancer Research
🇺🇸New York, New York, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States