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

August 6, 2026 updated by: Incyte Corporation

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

This study is being conducted to evaluate the safety, tolerability, and 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
160

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Incyte Corporation Call Center (US)
  • Phone Number: 1.855.463.3463
  • Email: medinfo@incyte.com

Study Contact Backup

  • Name: Incyte Corporation Call Center (ex-US)
  • Phone Number: +800 00027423
  • Email: eumedinfo@incyte.com

Study Locations

  • Australia
    • Queensland
      • Herston, Queensland, Australia, 04029
        • Royal Brisbane and Women's Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 05000
        • Royal Adelaide Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 03000
        • Peter MacCallum Cancer Centre
      • Melbourne, Victoria, Australia, 03004
        • The Alfred Hospital
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Center
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Hopital Maisonneuve-Rosemont, Montreal, Qc
  • Denmark
      • Roskilde, Denmark, 04000
        • Sjaellands Universitetshospital
      • Vejle, Denmark, 07100
        • Vejle Hospital
  • France
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Nîmes, France, 30029
        • CHU Nimes
      • Paris, France, 75010
        • Hospital Saint Louis
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Aachen, Germany, 52074
        • University Medical Center Rwth Aachen
      • Halle, Germany, 06120
        • Universitätsklinikum Halle (Saale)
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm
  • Italy
      • Bologna, Italy, 40138
        • Aou Policlinico S. Orsola-Malpighi
      • Florence, Italy, 50134
        • Azienda Ospedaliero-Universitaria Careggi (Aouc)
      • Milan, Italy, 20122
        • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Japan
      • Chiba-ken, Japan, 277-0882
        • National Cancer Center Hospital East
      • Kagoshima, Japan, 890-8520
        • Kagoshima University Hospital
      • Osaka, Japan, 545-8586
        • Osaka Metropolitan university Hospital
      • Tokyo, Japan, 113-8603
        • Nippon Medical School Hospital
      • Tsu, Japan, 514-0001
        • Mie University Hospital
  • Spain
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Valencia, Spain, 46026
        • Hospital Universitari I Politècnic La Fe
  • United Kingdom
      • London, United Kingdom, SE1 9RT
        • Guys and St Thomas NHS Foundation Trust
      • Manchester, United Kingdom, M20 4BV
        • The Christie Nhs Foundation Trust Uk
      • Oxford, United Kingdom, OX3 7LE
        • University of Oxford

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 and ET as defined in the protocol.

Exclusion Criteria:

  • Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
  • Active invasive malignancy over the previous 2 years.
  • Active HBV/HCV, HIV.
  • History of clinically significant or uncontrolled cardiac disease.
  • Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
  • Laboratory values outside the Protocol-defined ranges.
  • 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.
  • Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
  • 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 within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
  • For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1a Dose Escalation Cohort Disease Group A - with MF
INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) will enroll in this group.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: Part 1a Dose Escalation Cohort Disease Group A - with ET
INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with with essential thrombocythemia (ET) will enroll in this group.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: 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.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: 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.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Drug: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Other Names:
  • Jakafi
Experimental: 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.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: 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.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Drug: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Other Names:
  • Jakafi
Experimental: 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.
Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Drug: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Other Names:
  • Jakafi

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with Dose Limiting Toxicities (DLTs)
Time Frame: Up to 28 days
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Up to 28 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to 3 years and 60 days
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with ruxolitinib
Up to 3 years and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation
Time Frame: Up to 3 years and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation.
Up to 3 years and 60 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
Time Frame: Up to 3 years and 60 days
Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.
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 3 years and 60 days
Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
Up to 3 years and 60 days
Participants with MF with symptomatic anemia: Anemia Response
Time Frame: Up to 3 years and 60 days
For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.
Up to 3 years and 60 days
Participants With ET: Response Rate
Time Frame: Up to 3 years and 60 days
Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Up to 3 years and 60 days
Participants With ET: Mean change from baseline of total symptom score (TSS)
Time Frame: Up to 3 years and 60 days
Mean change of TSS from baseline.
Up to 3 years and 60 days
Mean change in disease-related allele burden
Time Frame: Up to 3 years and 60 days
Mean change in disease-related allele burden.
Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmax of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as maximum observed plasma concentration of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: Tmax of INCA033989
Time Frame: Up to 3 years and 60 days
Defined as the time to reach the maximum plasma concentration of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmin of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as the minimum observed plasma concentration of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC(0-t) of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: CL/F of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as the apparent oral dose clearance of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: Vz/F of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as the apparent oral dose volume of distribution of INCA33989.
Up to 3 years and 60 days
Pharmacokinetics Parameter: t1/2 of INCA33989
Time Frame: Up to 3 years and 60 days
Defined as the apparent terminal phase disposition half-life of INCA33989.
Up to 3 years and 60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Incyte Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Incyte Medical Monitor, Incyte Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 25, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 29, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 29, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 21, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 7, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • INCA 33989-101
  • 2022-502514-86-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

IPD Sharing Time Frame

Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.

IPD Sharing Access Criteria

Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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