Clinical trial NCT07008118: A Study to Evaluate INCA035784 in Participants With Myeloproliferative Neoplasms
Official title: A Phase 1, Open-Label, Multicenter Study of INCA035784 in Participants With Myeloproliferative Neoplasms
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Myeloproliferative Neoplasms
Keywords: Myeloproliferative Neoplasms
Myelofibrosis
Essential thrombocythemia
CALR mutation
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2025-06-06
Enrollment: 120
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 evaluate the safety and tolerability of INCA035784 in participants with myeloproliferative neoplasms.


Eligibility criteria: 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
* 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/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 approximately 2 years and 90 days
measure: Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay
timeFrame: Up to approximately 2 years and 90 days
Secondary outcomes:
measure: Number of participants with TEAEs leading to dose modification or discontinuation
timeFrame: Up to approximately 2 years and 90 days
measure: 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)
timeFrame: Up to approximately 2 years and 90 days
measure: Participants with essential thrombocythemia (ET): Response using the revised IWG-MRT and ELN response criteria for ET
timeFrame: Up to approximately 2 years and 90 days
measure: Participants with myelodysplastic syndrome (MDS)/MPN: Response using the revised IWG-MRT response criteria for MDS/MPN
timeFrame: Up to approximately 2 years and 90 days
measure: Participants with symptomatic anemia: Anemia response
timeFrame: Up to approximately 2 years and 90 days
measure: Participants with spleen volume (SV) ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 35% (SVR35)
timeFrame: Week 12 and Week 24
measure: Participants with SV ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 25% (SVR25)
timeFrame: Week 12 and Week 24
measure: Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)
timeFrame: Week 12 and Week 24
measure: Mean change from baseline in TSS
timeFrame: Week 12 and Week 24
measure: Pharmacokinetics Parameter (PK): Cmax of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: Tmax of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: Cmin of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: AUC(0-t) of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: AUC 0-∞ of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: CL of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: Vz of INCA035784
timeFrame: Up to approximately 2 years and 90 days
measure: Pharmacokinetics Parameter: t1/2 of INCA035784
timeFrame: Up to approximately 2 years and 90 days
Other outcomes:
Locations:
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: