A Study to Evaluate INCA035784 in Participants With Myeloproliferative Neoplasms

Phase 1RecruitingNCT07008118

Incyte Corporation120 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Myeloproliferative Neoplasms

Interventions

INCA035784DRUG

INCA035784 will be administered at the assigned dose in the dose escalation part and at the protocol defined dose in the dose expansion part.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (16)

Mayo Clinic Hospital

Phoenix, Arizona, United States

NOT_YET_RECRUITING

Stanford University

Outcomes

Primary Outcomes

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 Outcomes

Number of participants with TEAEs leading to dose modification or discontinuation

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)

Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.

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

Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.

Central Contacts

Incyte Corporation Call Center (US)

CONTACT

1.855.463.3463 medinfo@incyte.com

Incyte Corporation Call Center (ex-US)

CONTACT

+800 00027423 eumedinfo@incyte.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Palo Alto, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

RECRUITING

Mayo Clinic-Florida

Jacksonville, Florida, United States

NOT_YET_RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

NOT_YET_RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

NOT_YET_RECRUITING

Icahn School of Medicine At Mount Sinai

New York, New York, United States

RECRUITING

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, United States

RECRUITING

South Austin Medical Center

Austin, Texas, United States

RECRUITING

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

Dallas, Texas, United States

NOT_YET_RECRUITING

...and 6 more locations

Time frame: Up to approximately 2 years and 90 days

Participants with symptomatic anemia: Anemia response

Anemia response as defined in the protocol.

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)

Defined as percentage of participants with a protocol defined 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)

Defined as percentage of participants with a protocol defined 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)

Defined as the percentage of participants achieving ≥ 50% reduction from baseline of TSS.

Time frame: Week 12 and Week 24

Mean change from baseline in TSS

Mean change of TSS from baseline.

Time frame: Week 12 and Week 24

Pharmacokinetics Parameter (PK): Cmax of INCA035784

Defined as maximum observed plasma concentration of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: Tmax of INCA035784

Defined as the time to reach the maximum plasma concentration of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: Cmin of INCA035784

Defined as the minimum observed plasma concentration of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: AUC(0-t) of INCA035784

Defined as the area under the concentration-time curve up to the last measurable concentration of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: AUC 0-∞ of INCA035784

Defined as the area under the concentration-time curve from 0 to infinity of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: CL of INCA035784

Defined as the apparent oral dose clearance of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: Vz of INCA035784

Defined as the apparent oral dose volume of distribution of INCA035784.

Time frame: Up to approximately 2 years and 90 days

Pharmacokinetics Parameter: t1/2 of INCA035784

Defined as the apparent terminal phase disposition half-life of INCA035784.

Time frame: Up to approximately 2 years and 90 days