Clinical trial NCT06313593: A Study to Evaluate the Safety, Tolerability of INCB160058 in Participants With Myeloproliferative Neoplasms
Official title: A Phase 1, Open-Label, Multicenter Study of INCB160058 in Participants With Myeloproliferative Neoplasms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Myeloproliferative Neoplasms
Keywords: Myeloproliferative Neoplasms
INCB160058
Myelofibrosis
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2024-03-15
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 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.

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.

Primary outcomes:
measure: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years and 30 days
measure: Number of participants with TEAEs leading to dose modification or discontinuation
timeFrame: Up to 2 years and 30 days
Secondary outcomes:
measure: INCB160058 pharmacokinetic (PK) in Plasma
timeFrame: Up to Day 57
measure: For participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
timeFrame: Week 12 and 24 and then every 24 weeks up to 2 years
measure: For participants with MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
timeFrame: Week 12 and Week 24
measure: For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV
timeFrame: Week 12 and 24 and then every 24 weeks up to 2 years
measure: For participants with ET: Response using revised IWG-MRT and ELN response criteria for ET
timeFrame: Week 12 and 24 and then every 24 weeks up to 2 years
measure: For all participants: Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)
timeFrame: Week 24
measure: 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.
timeFrame: Week 12 and Week 24
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Fairway
country: United States
facility: The University of Kansas Cancer Center Kucc University of Kansas Clinical Research Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine At Mount Sinai
state: New York
city: New York
country: United States
facility: Sloan Kettering Institute For Cancer Research
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Montreal
country: Canada
facility: McGill University Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont, Montreal, Qc
state: Quebec
city: Paris
country: France
facility: Hospital Saint Louis
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Aachen
country: Germany
facility: University Medical Center Rwth Aachen
city: Halle
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: Bologna
country: Italy
facility: Aou Policlinico S. Orsola-Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi (Aouc)
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Bern
country: Switzerland
facility: Inselspital - Universitaetsspital Bern
city: Zuerich
country: Switzerland
facility: Universitatsspital Zurich
city: London
country: United Kingdom
facility: Guys and St Thomas Nhs Foundation Trust
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical
role: STUDY_DIRECTOR
References: