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

Overview

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

Interventions

• Drug INCB160058
  Oral; Tablet
• Drug Standard disease-directed therapy
  A standard disease-directed therapy will be administered according to Prescribing Information/SmPC.

Primary outcome measures

• Number of participants with Dose Limiting Toxicities (DLTs) [Time frame: Up to 28 days]
• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to 2 years and 30 days]
• Number of participants with TEAEs leading to dose modification or discontinuation [Time frame: Up to 2 years and 30 days]

Secondary outcome measures (7)

• INCB160058 and a standard disease-directed therapy pharmacokinetic (PK) in Plasma [Time frame: Up to Day 57]
• For participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF [Time frame: 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 [Time frame: Week 12 and Week 24]
• For participants with PV: Response using revised IWG-MRT and ELN response criteria for PV [Time frame: 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 [Time frame: 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) [Time frame: 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. [Time frame: Week 12 and Week 24]

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 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 13 centers

• The University of Alabama At Birmingham — Birmingham
• Stanford University — Palo Alto
• Moffitt Cancer Center — Tampa
• Northwestern University — Chicago
• The University of Kansas Cancer Center Kucc University of Kansas Clinical Research Center — Fairway
• University of Michigan — Ann Arbor
• Cornell Medical Center — New York
• Icahn School of Medicine At Mount Sinai — New York
• … and 5 more centers

Canada · 3 centers

• Princess Margaret Cancer Center — Toronto
• Hopital Maisonneuve-Rosemont, Montreal, Qc — Montreal
• McGill University Jewish General Hospital — Montreal

Germany · 3 centers

• University Medical Center Rwth Aachen — Aachen
• Universitatsklinikum Essen — Essen
• Universitatsklinikum Halle (Saale) — Halle

Italy · 3 centers

• Aou Policlinico S. Orsola-Malpighi — Bologna
• Azienda Ospedaliero-Universitaria Careggi (Aouc) — Florence
• Fondazione Irccs Ca Granda Ospedale Maggiore — Milan

France · 2 centers

• Hospital Saint Louis — Paris
• Institut Gustave Roussy — Villejuif

Norway · 2 centers

• Haukeland University Hospital — Bergen
• Oslo University Hospital — Oslo

Switzerland · 2 centers

• Inselspital - Universitaetsspital Bern — Bern
• Universitatsspital Zurich — Zurich

United Kingdom · 2 centers

• Guys and St Thomas Nhs Foundation Trust — London
• Genesiscare Oxford — Oxford

Identifiers

NCT: NCT06313593 · INCB160058-101 · 2024-520353-21-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗