RecruitingInterventionalPhase 1

A Phase 1, Open-Label, Multicenter Study of INCA035784 in Participants With Myeloproliferative Neoplasms

NCT ID: NCT07008118Sponsor: Incyte CorporationLast updated: 2026-04-06

Summary

This study is being conducted to evaluate the safety and tolerability of INCA035784 in participants with myeloproliferative neoplasms.

Arms & 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.

Outcome measures

Primary

Number of participants with Dose Limiting Toxicities (DLTs)
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Time frame: Up to 28 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: Up to approximately 2 years and 90 days
Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay
Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay.
Time frame: Up to approximately 2 years and 90 days

Secondary

Number of participants with TEAEs leading to dose modification or discontinuation
Time frame: Up to approximately 2 years and 90 days
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)
Time frame: Up to approximately 2 years and 90 days
Participants with essential thrombocythemia (ET): Response using the revised IWG-MRT and ELN response criteria for ET
Time frame: Up to approximately 2 years and 90 days
Participants with symptomatic anemia: Anemia response
Time frame: Up to approximately 2 years and 90 days
Participants with spleen volume (SV) ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 35% (SVR35)
Time frame: Week 12 and Week 24
Participants with SV ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 25% (SVR25)
Time frame: Week 12 and Week 24
Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS)
Time frame: Week 12 and Week 24
Mean change from baseline in TSS
Time frame: Week 12 and Week 24
Pharmacokinetics Parameter (PK): Cmax of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: Tmax of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: Cmin of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: AUC(0-t) of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: AUC 0-∞ of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: CL of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: Vz of INCA035784
Time frame: Up to approximately 2 years and 90 days
Pharmacokinetics Parameter: t1/2 of INCA035784
Time frame: Up to approximately 2 years and 90 days

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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/Exclusion Criteria may apply.

Study locations (12)

Mayo Clinic Hospital

Phoenix, Arizona, 85054

Not Yet Recruiting

Stanford University

Palo Alto, California, 94304

Recruiting

Colorado Blood Cancer Institute

Denver, Colorado, 80218

Recruiting

Mayo Clinic-Florida

Jacksonville, Florida, 32224

Not Yet Recruiting

University of Chicago Medical Center

Chicago, Illinois, 60637

Not Yet Recruiting

Johns Hopkins University

Baltimore, Maryland, 21287

Not Yet Recruiting

Icahn School of Medicine At Mount Sinai

New York, New York, 10029

Recruiting

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27514

Recruiting

South Austin Medical Center

Austin, Texas, 78704

Recruiting

University of Texas Southwestern Medical Center Harold C Simmons Comprehensive Cancer Center Blood

Dallas, Texas, 75235

Not Yet Recruiting

Huntsman Cancer Institute At University of Utah

Salt Lake City, Utah, 84112

Recruiting

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting