Myeloproliferative Neoplasms
Conditions
Keywords
Myeloproliferative Neoplasms, Myelofibrosis, Essential thrombocythemia, CALR mutation
Brief summary
This study is being conducted to evaluate the safety and tolerability of INCA035784 in participants with myeloproliferative neoplasms.
Interventions
DRUGINCA035784
INCA035784 will be administered at the assigned dose in the dose escalation part and at the protocol defined dose in the dose expansion part.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older at the time of signing the ICF * ECOG performance status of 0 to 1 for the dose escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b) * Documented CALR exon-9 mutation * Confirmed diagnosis of MPN according to the 2022 ICC criteria: * DIPSS+ intermediate-2/high-risk MF with prior JAKi, \<20% blasts, and measurable spleen * High-risk ET with platelets \>450×10⁹/L * Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET (unless only a single standard-of-care option is approved in the participating country) * No prior stem cell transplant and none planned within 6 months * Minimum Laboratory Requirements: * Platelet count ≥50 × 10⁹/L * Absolute neutrophil count ≥1 × 10⁹/L * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN), unless receiving vitamin K antagonists * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 × ULN * Total bilirubin \<2 × ULN * Estimated creatinine clearance \>45 or \>30 mL/min (depending on study part)
Exclusion criteria
* Major bleeding or thrombosis (e.g., stroke, DVT, PE) within the past 3 months * Active or high-risk HBV, HCV, or HIV infection, or other chronic active infections requiring systemic treatment * Active invasive cancer within the past 2 years, except certain early-stage or low-risk cancers (e.g., resected skin, cervical, thyroid, or prostate cancer) * Pregnant or unwilling to avoid pregnancy or fathering a child during the study and for a defined period after the last dose. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to approximately 2 years and 90 days | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after the last dose of study drug. |
| Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay | Up to approximately 2 years and 90 days | Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with TEAEs leading to dose modification or discontinuation | Up to approximately 2 years and 90 days | Number of participants with TEAEs leading to dose modification or discontinuation. |
| Participants with MF: Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria for myelofibrosis (MF) | Up to approximately 2 years and 90 days | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. |
| Participants with essential thrombocythemia (ET): Response using the revised IWG-MRT and ELN response criteria for ET | Up to approximately 2 years and 90 days | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. |
| Participants with symptomatic anemia: Anemia response | Up to approximately 2 years and 90 days | Anemia response as defined in the protocol. |
| Participants with spleen volume (SV) ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 35% (SVR35) | Week 12 and Week 24 | Defined as percentage of participants with a protocol defined Spleen Volume Reduction of ≥ 35% (SVR35). |
| Participants with SV ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 25% (SVR25) | Week 12 and Week 24 | Defined as percentage of participants with a protocol defined Spleen Volume Reduction of ≥ 25% (SVR25). |
| Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS) | Week 12 and Week 24 | Defined as the percentage of participants achieving ≥ 50% reduction from baseline of TSS. |
| Mean change from baseline in TSS | Week 12 and Week 24 | Mean change of TSS from baseline. |
| Pharmacokinetics Parameter (PK): Cmax of INCA035784 | Up to approximately 2 years and 90 days | Defined as maximum observed plasma concentration of INCA035784. |
| Pharmacokinetics Parameter: Tmax of INCA035784 | Up to approximately 2 years and 90 days | Defined as the time to reach the maximum plasma concentration of INCA035784. |
| Pharmacokinetics Parameter: Cmin of INCA035784 | Up to approximately 2 years and 90 days | Defined as the minimum observed plasma concentration of INCA035784. |
| Pharmacokinetics Parameter: AUC(0-t) of INCA035784 | Up to approximately 2 years and 90 days | Defined as the area under the concentration-time curve up to the last measurable concentration of INCA035784. |
| Pharmacokinetics Parameter: AUC 0-∞ of INCA035784 | Up to approximately 2 years and 90 days | Defined as the area under the concentration-time curve from 0 to infinity of INCA035784. |
| Pharmacokinetics Parameter: CL of INCA035784 | Up to approximately 2 years and 90 days | Defined as the apparent oral dose clearance of INCA035784. |
| Pharmacokinetics Parameter: Vz of INCA035784 | Up to approximately 2 years and 90 days | Defined as the apparent oral dose volume of distribution of INCA035784. |
| Pharmacokinetics Parameter: t1/2 of INCA035784 | Up to approximately 2 years and 90 days | Defined as the apparent terminal phase disposition half-life of INCA035784. |
Countries
Australia, Belgium, Germany, Italy, United States
Contacts
CONTACTIncyte Corporation Call Center (US)
CONTACTIncyte Corporation Call Center (ex-US)
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed