A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

NCT ID: NCT06034002

Last Updated: 2025-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-04

Study Completion Date

2028-10-29

Brief Summary

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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.

Detailed Description

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Conditions

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Myeloproliferative Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1a Dose Escalation Cohort Disease Group A - with MF

INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) will enroll in this group.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Part 1a Dose Escalation Cohort Disease Group A - with ET

INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with essential thrombocythemia (ET) will enroll in this group.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R

INCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Ruxolitinib

Intervention Type DRUG

Rux will be administered according to Prescribing Information/SmPC.

Part 1b: Dose Expansion - with MF

INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Part 1b: Dose Expansion - with TGB-MF SubOpt R

INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Ruxolitinib

Intervention Type DRUG

Rux will be administered according to Prescribing Information/SmPC.

Part 1b: Dose Expansion - with ET

INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Part 1c: Dose Expansion

INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.

Group Type EXPERIMENTAL

INCA033989

Intervention Type DRUG

INCA033989 will be administered at protocol defined dose.

Ruxolitinib

Intervention Type DRUG

Rux will be administered according to Prescribing Information/SmPC.

Interventions

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INCA033989

INCA033989 will be administered at protocol defined dose.

Intervention Type DRUG

Ruxolitinib

Rux will be administered according to Prescribing Information/SmPC.

Intervention Type DRUG

Other Intervention Names

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Jakafi

Eligibility Criteria

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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 HBV/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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Incyte Medical Monitor

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status RECRUITING

Stanford Cancer Institute

Palo Alto, California, United States

Site Status RECRUITING

University of Miami Health System

Miami, Florida, United States

Site Status RECRUITING

The University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Icahn School of Medicine At Mount Sinai

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Md Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Incyte Corporation Call Center (US)

Role: CONTACT

1.855.463.3463

Incyte Corporation Call Center (ex-US)

Role: CONTACT

+800 00027423

Related Links

Other Identifiers

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INCA33989-102

Identifier Type: -

Identifier Source: org_study_id

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