RecruitingInterventionalPhase 1

A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

NCT ID: NCT06034002Sponsor: Incyte CorporationLast updated: 2026-04-17

Summary

This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a Monotherapy or in Combination With Ruxolitinib in participants with myeloproliferative neoplasms.

Arms & interventions

DrugINCA033989
INCA033989 will be administered at protocol defined dose.
DrugRuxolitinib
Rux will be administered according to Prescribing Information/SmPC.

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, including those leading to dose modification or discontinuation.
Time frame: Up to 3 years and 60 days

Secondary

Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
Time frame: Up to 3 years and 60 days
Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
Time frame: Up to 24 weeks
Participants with symptomatic anemia: Anemia Response as defined in the protocol
Time frame: Up to 24 weeks
Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET
Time frame: Up to 3 years and 60 days
Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation
Time frame: Up to 3 years and 60 days
Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS)
Time frame: Week 12 and Week 24
Mean change from baseline in TSS
Time frame: Week 12 and Week 24
Mean change in disease-related allele burden
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmin of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC(0-t) of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC 0-∞ of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: CL/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Vz/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: t1/2 of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Time frame: Up to 3 years and 60 days

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Life expectancy \> 6 months. * Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease). * Existing documentation from a qualified local laboratory of CALR exon-9 mutation. * Participants with MF or ET as defined in the protocol. Exclusion Criteria: * Presence of any hematological malignancy other than ET, PMF, or post-ET MF. * Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment. * Participants with laboratory values exceeding the protocol defined thresholds. * Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned. * Active invasive malignancy over the previous 2 years. * History of clinically significant or uncontrolled cardiac disease. * Active or chronic HBV or active HCV or known history of HIV. * Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. * Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment. Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study locations (13)

City of Hope Medical Center

Duarte, California, 91010

Recruiting

Stanford Cancer Institute

Palo Alto, California, 94304

Recruiting

University of Miami Health System

Miami, Florida, 33136

Recruiting

The University of Kansas Cancer Center

Westwood, Kansas, 66205

Recruiting

Johns Hopkins Hospital

Baltimore, Maryland, 21287

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Washington University School of Medicine

St Louis, Missouri, 63108

Recruiting

Icahn School of Medicine At Mount Sinai

New York, New York, 10029

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157

Recruiting

Cleveland Clinic

Cleveland, Ohio, 44195

Recruiting

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

Recruiting

Md Anderson Cancer Center

Houston, Texas, 77030

Recruiting