Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (LIMBER)

January 10, 2024 updated by: Incyte Corporation

A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of INCB057643 as monotherapy or combination with ruxolitinib for participants with myelofibrosis (MF) and other myeloid neoplasms.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

216

Phase

  • 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

  • Name: Incyte Corporation Call Center (US)
  • Phone Number: 1.855.463.3463
  • Email: medinfo@incyte.com

Study Contact Backup

Study Locations

    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z2A5
        • Recruiting
        • St Paul's Hospital
    • Ontario
      • Toronto, Ontario, Canada, MG5 2R2
        • Recruiting
        • Princess Margaret Cancer Center
      • Helsinki, Finland, 00029
        • Recruiting
        • Helsinki University Central Hospital
      • Bologna, Italy, 40138
        • Recruiting
        • L Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
      • Firenze, Italy, 50134
        • Recruiting
        • Azienda Ospedaliero-Universitaria Careggi (Aouc)
      • Meldola, Italy, 47014
        • Not yet recruiting
        • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
      • Milan, Italy, 20122
        • Recruiting
        • Fondazione Irccs Ca Granda Ospedale Maggiore
      • Orbassano, Italy, 10043
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
      • Verona, Italy, 371134
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria Integrata Di Verona - Centro Ricerche Cliniche Dr Verona
      • Aichi, Japan, 470-1192
        • Completed
        • Fujita Health University Hospital
      • Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
      • Chiba, Japan, 260-8677
        • Recruiting
        • Chiba University Hospital
      • Chuo, Japan, 409-3898
        • Recruiting
        • University of Yamanashi Hospital
      • Fukuoka, Japan
        • Completed
        • Kyushu University Hospital
      • Badalona, Spain, 08916
        • Recruiting
        • Ico Hospital Germans Trias I Pujol
      • Las Palmas, Spain, 35019
        • Recruiting
        • Hospital Universitario Insular de Gran Canaria
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Murcia, Spain, 30120
        • Recruiting
        • Hospital Universitario Virgen de la Arrixaca
      • Salamanca, Spain, 37007
        • Recruiting
        • Hospital Clinico Universitario de Salamanca
      • Boston, United Kingdom, PE21 9QS
        • Not yet recruiting
        • United Lincolnshire Hospitals
      • Manchester, United Kingdom, M20 4BV
        • Recruiting
        • The Christie Nhs Foundation Trust Uk
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • University of Oxford
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Cancer Center
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Sylvester Comprehensive Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University-Winship Cancer Institute
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10065
        • Withdrawn
        • Weill Medical College of Cornell University
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Recruiting
        • University of North Carolina at Chapel Hill
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Completed
        • University of Cincinnati Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute at University of Utah
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Seattle Cancer Care Alliance

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 years and older at the time of signing the informed consent.
  • Part 1 Monotherapy: Participants with confirmed diagnosis of relapsed or refractory MF (primary, or post-PV and post-ET), MDS, MDS/MPN, or ET who have received at least 1 prior line of therapy; are either refractory, relapsed, or intolerant to the last therapy; and there is no available therapy that would provide clinical benefit in the opinion of the investigator.

    • a. MF with measurable disease (palpable spleen and symptoms) as defined in the protocol and risk category of intermediate 2 or high according to DIPSS. MF participants must have received a JAK inhibitor(s), such as ruxolitinib.
    • b. ET participants should have disease refractory to hydroxyurea as defined by the protocol.
  • Part 2 Combination with ruxolitinib.

    • a. Primary MF or secondary MFs (post-PV MF and post-ET MF), histologically or cytologically confirmed, with measurable disease (palpable spleen and symptoms) as defined in the protocol, either currently receiving ruxolitinib with suboptimal response or JAKi-naive.
    • b. Suboptimal response is defined as currently being treated with ruxolitinib monotherapy at a stable dose for ≥ 8 weeks immediately preceding the first dose of study treatment. One dose reduction due to toxicities within 8 weeks prior to Study Day 1 is permitted.
    • c. JAKi-naive is defined as those participants that have no prior use of any JAK inhibitor, including ruxolitinib, and;
    • d. Part 2 dose escalation: Risk category of intermediate-2 or high according to DIPSS.
    • e. Part 2 dose expansion: Risk category of intermediate-1, intermediate-2, or high according to DIPSS.
    • f. Part 2 dose expansion participants with chronic MF are defined as participants with bone marrow myeloblast percentage < 5% and no blasts detected/not persistent blast count in peripheral blood at screening or baseline, AND who are currently receiving ruxolitinib and having suboptimal response.
    • g.Part 2 dose expansion participants with accelerated-phase MF are defined as having either a bone marrow myeloblast percentage ≥ 5% to < 20% or a myeloblast percentage ≥ 10% in peripheral blood on 2 occasions at least 2 weeks apart, AND are currently receiving ruxolitinib and have a suboptimal response.
    • h.Part 2 dose expansion participants with JAKi-naive MF are eligible to receive ruxolitinib, with peripheral blood blast count of < 10% at the screening hematology assessment.
  • Must not be a candidate for potentially curative therapy, including hematopoietic stem cell transplantation.
  • ECOG performance status 0 to 2.
  • Life expectancy ≥ 24 weeks.
  • Willingness to avoid pregnancy or fathering children based on criteria.

    • a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
    • b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
    • c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea without any other medical reasons such as treatment with anticancer agents) are eligible.

Exclusion Criteria:

  • Prior receipt of a BET inhibitor.
  • Receipt of anticancer medications or investigational drugs within the protocol-defined interval before the first dose of study treatment. For Part 2 JAKi-naive, prior use of a JAK inhibitor (including ruxolitinib) and no use of experimental drug therapy for MF or any other standard drug (except hydroxyurea) used for MF or another indication within 3 months of starting study drug. Hydroxyurea must be discontinued 3 weeks prior to starting study treatment. For participants with suboptimal response to ruxolitinib, ruxolitinib will continue at the participants' current ongoing doses, no ruxolitinib washout is needed.
  • Participants with exclusionary laboratory values at screening defined as, including, but not limited to,

    • a. Platelets. Part 1 (monotherapy dose expansion, MF): < 75 × 109/L. Part 1 (monotherapy dose expansion, ET): < 450 × 109/L. Part 2 (combination dose escalation and expansion): < 75 × 109/L. Part 2 (combination dose expansion, JAKi-naïve MF): < 100 × 109/L.
    • b. Hemoglobin: Participants unwilling to receive red blood cell transfusion to treat low hemoglobin levels are excluded.
    • c. ANC < 0.75 × 109/L.
  • inadequate renal, hepatic and coagulation functions as defined in the protocol.
  • Concurrent anticancer therapy other than the therapies being tested in this study.
  • Participants who have received allogeneic hematopoietic stem cell transplantation within 6 months of enrollment (unless approved by the medical monitor), or have active graft versus-host disease, or have received immunosuppressive therapy following allogeneic transplant within 2 weeks of the first dose of study treatment.
  • Unless approved by the medical monitor, may not have received autologous hematopoietic stem-cell transplant within 3 months before the first dose of study treatment.
  • Significant concurrent, uncontrolled medical condition, including but not limited to, significant GI disorder, history of or current clinically significant or uncontrolled cardiac disease, history or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful, and history of bleeding disorder or at a high risk of bleeding.
  • Active bacterial, fungal, parasitic, or viral infection that requires therapy.
  • Current use of prohibited medication as described in the protocol, including the use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment.

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 : INCB057643 Monotherapy
INCB057643 dose escalation and dose expansion
INCB057643 dose escalation and dose expansion.
Experimental: Part 2 : INCB057643 Combination with Ruxolitinib
Combination arm in dose escalation and dose expansion
INCB057643 dose escalation and dose expansion.
Ruxolitinib will be administered twice a day using the dose described for each Cohort in the protocol for Part 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of treatment-emergent adverse events
Time Frame: Up to approximately 9 months
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 approximately 9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peripheral Blast Complete Remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
Defined as peripheral blasts achieving the protocol defined criteria.
Up to approximately 9 months
Peripheral Blast Partial Remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
Defined as peripheral blast achieving the protocol defined criteria.
Up to approximately 9 months
Durable Blast Complete or Partial remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
Defined as achieving the protocol defined criteria.
Up to approximately 9 months
Symptom Response Rate (MF or ET)
Time Frame: Week 24
Defined as the proportion of participants who achieve a protocol defined reduction in Total Symptomatic Score (TSS) relative to baseline as measured by the MPN-symptom assessment form (SAF) TSS.
Week 24
Anemia Response (MF only)
Time Frame: Up to approximately 9 months
A hemoglobin increase of 1.5 g/dL relative to baseline for any "rolling" 12-week period during the study treatment period, if transfusion independent (TI) at baseline or Achieving TI for any "rolling" 12-week period during the study treatment period, if transfusion dependent (TD) at baseline.
Up to approximately 9 months
Duration of Anemia Response (MF only)
Time Frame: Up to approximately 9 months
The interval from the first onset of anemia response to the earliest date of loss of anemia response that persists for at least 4 weeks or death from any cause for the TI participants at baseline or duration of RBC-TI period for participants achieving RBC-TI for at least 12 consecutive weeks during the study treatment period for the TD participants at baseline.
Up to approximately 9 months
Changes in hemoglobin value from baseline (MF only)
Time Frame: Up to approximately 9 months
Defined as the mean change from baseline in the hemoglobin value over 12-week treatment periods.
Up to approximately 9 months
Red Blood Cell (RBC) Transfusion Burden (MF only)
Time Frame: Up to approximately 9 months
Defined as the average number of RBC units per participant-month through Weeks 12, 24, and 48.
Up to approximately 9 months
Overall response (ET only)
Time Frame: Up to approximately 9 months
Defined as proportion of participants with complete response or partial response and hematological improvement/response as per definition for ET.
Up to approximately 9 months
Duration of platelet count reduction or White Blood Cell (WBC) count reduction (ET only)
Time Frame: Up to approximately 9 months
Defined as platelet count reduction or WBC count reduction lasting ≥ 12 weeks.
Up to approximately 9 months
Spleen Volume Response
Time Frame: Week 24
Defined as achieving a protocol defined reduction at Week 24 relative to baseline as measured by MRI or CT scan.
Week 24
Duration of a Spleen Volume Response from baseline (MF only)
Time Frame: Up to approximately 9 months
Defined as the interval between the first spleen volume response and the date of the first measurement that no longer achieves the protocol defined criteria.
Up to approximately 9 months
Bone Marrow (BM) Blast Complete Remission (MF, myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm (MPN))
Time Frame: Up to approximately 9 months
Defined as BM blasts achieving the protocol defined criteria.
Up to approximately 9 months
BM Blast Partial Remission (MF, MDS, and MDS/MPN)
Time Frame: Up to approximately 9 months
Defined as BM blasts achieving the protocol defined criteria.
Up to approximately 9 months

Collaborators and Investigators

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

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)

February 23, 2021

Primary Completion (Estimated)

November 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

February 18, 2020

First Submitted That Met QC Criteria

February 20, 2020

First Posted (Actual)

February 21, 2020

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 10, 2024

Last Verified

January 1, 2024

More Information

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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