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MyelofibrosisPhase 1LIMBERNCT04279847

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

A Phase 1 study testing INCB057643 and Ruxolitinib in people with Myelofibrosis and Myelodysplastic Syndrome, run by Incyte Corporation at 48 sites in 8 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
INCB057643 and Ruxolitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
48 sitesin 8 countries
Study dates
23 Feb 2021to 30 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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% (not applicable if dry tap or blast count deemed not reliable by the investigator) and blast count in peripheral blood < 1% at screening and who are currently receiving ruxolitinib and having a suboptimal response.
  • Note: Study treatment should be delayed if peripheral blood blast count at baseline is > 3%; treatment should only be started with medical monitor approval.
  • 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.

Who cannot join

  • 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. 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.
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  • 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.

Trial locations and contacts

48 sites in 8 countries.

48 sites in 8 countries

United States19 sites

  • Emory University-Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • University of Alabama At Birmingham

    Birmingham, Alabama, 35294

  • University of North Carolina At Chapel Hill

    Chapel Hill, North Carolina, 27514

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio, 45267

  • Ohio State University

    Columbus, Ohio, 43210

  • Texas Oncology-Baylor Sammons Cancer Center

    Dallas, Texas, 75246

  • Md Anderson Cancer Center

    Houston, Texas, 77030

  • Oncology Consultants

    Houston, Texas, 77030

  • University of Iowa Hospital and Clinics

    Iowa City, Iowa, 52242

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Nyu Langone Health - Long Island Hospital

    Mineola, New York, 11501

  • Rutgers Cancer Institute of Nj

    New Brunswick, New Jersey, 08901

  • Nyu Langone Laura and Isaac Perlmutter Cancer Center

    New York, New York, 10016

  • Weill Medical College of Cornell University

    New York, New York, 10021

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Huntsman Cancer Institute At University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Italy6 sites

  • Aou Policlinico S. Orsola-Malpighi

    Bologna, 40138

  • Azienda Ospedaliero-Universitaria Careggi (Aouc)

    Florence, 50134

  • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori

    Meldola, 47014

  • Fondazione Irccs Ca Granda Ospedale Maggiore

    Milan, 20122

  • Azienda Ospedaliero Universitaria San Luigi Gonzaga Di Orbassano

    Orbassano, 10043

  • Centro Ricerche Cliniche Di Verona

    Verona, 37134

Other trials in Italy

Japan6 sites

  • Fujita Health University Hospital

    Aichi, 470-1192

  • Chiba University Hospital

    Chiba, 260-8677

  • National Cancer Center Hospital East

    Chiba, 277-8577

  • University of Yamanashi Hospital

    Chūō, 409-3898

  • Kyushu University Hospital

    Fukuoka

  • Kumamoto Shinto General Hospital

    Kumamoto, 862-8655

Other trials in Japan

Spain5 sites

  • Hospital Universitari Germans Trias I Pujol

    Badalona, 08916

  • Hospital Universitario de Gran Canaria Dr. Negrin

    Las Palmas de Gran Canaria, 35010

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen de La Arrixaca

    Murcia, 30120

  • Hospital Clinico Universitario de Salamanca

    Salamanca, 37007

Other trials in Spain

China4 sites

  • Peking Union Medical College Hospital

    Beijing, 100730

  • Nanfang Hospital_Southern Medical University

    Guangzhou, 510515

  • The First Affiliated Hospital, Zhejiang University School of Medicine (Fahzu)

    Hangzhou, 310003

  • Henan Cancer Hostipal

    Zhengzhou, 450003

Other trials in China

United Kingdom4 sites

  • United Lincolnshire Hospitals

    Boston, PE21 9QS

  • Lincoln County Hospital

    Lincoln, LN2 5QY

  • The Christie Nhs Foundation Trust Uk

    Manchester, M20 4BX

  • University of Oxford

    Oxford, OX3 7LE

Other trials in United Kingdom

Canada3 sites

  • McGill University Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 2M9

  • St Paul'S Hospital

    Vancouver, V6Z2A5

Other trials in Canada

Finland1 site

  • Helsinki University Central Hospital

    Helsinki, 00029

Other trials in Finland

About this study

Official title: 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.

Being tested
INCB057643, Ruxolitinib
Keywords
Myelofibrosis, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasm overlap syndrome, myeloproliferative neoplasm, BET protein inhibitor, relapsed primary myelofibrosis, refractory primary myelofibrosis, secondary myelofibrosis, post-polycythemia vera myelofibrosis, post-essential thrombocythemia myelofibrosis, LIMBER, ET (essential thrombocythemia)
Medical subject headings
Primary Myelofibrosis, Myelodysplastic Syndromes, Myeloproliferative Disorders, Recurrence, Thrombocythemia, Essential

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INCB057643Drug

    INCB057643 dose escalation and dose expansion.

  • RuxolitinibDrug

    Ruxolitinib will be administered twice a day using the dose described for each Cohort in the protocol for Part 2.

Study groups in NCT04279847
Study groupRoleWhat they receive
Part 1 : INCB057643 MonotherapyExperimentalINCB057643 dose escalation and dose expansion
Receives: Drug: INCB057643
Part 2 : INCB057643 Combination with RuxolitinibExperimentalCombination arm in dose escalation and dose expansion
Receives: Drug: INCB057643; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of treatment-emergent adverse events

    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.

    Measured: Up to approximately 9 months

Secondary outcomes (14)

  1. Spleen Volume Response

    Defined as achieving a protocol defined reduction at Week 24 relative to baseline as measured by MRI or CT scan.

    Measured: Week 24

  2. Duration of a Spleen Volume Response from baseline (MF only)

    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.

    Measured: Up to approximately 9 months

  3. Symptom Response Rate (MF or ET)

    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.

    Measured: Week 24

  4. Anemia Response (MF only)

    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.

    Measured: Up to approximately 9 months

  5. Duration of Anemia Response (MF only)

    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.

    Measured: Up to approximately 9 months

  6. Changes in hemoglobin value from baseline (MF only)

    Defined as the mean change from baseline in the hemoglobin value over 12-week treatment periods.

    Measured: Up to approximately 9 months

  7. Red Blood Cell (RBC) Transfusion Burden (MF only)

    Defined as the average number of RBC units per participant-month through Weeks 12, 24, and 48.

    Measured: Up to approximately 9 months

  8. Overall response (ET only)

    Defined as proportion of participants with complete response or partial response and hematological improvement/response as per definition for ET.

    Measured: Up to approximately 9 months

  9. Duration of platelet count reduction or White Blood Cell (WBC) count reduction (ET only)

    Defined as platelet count reduction or WBC count reduction lasting ≥ 12 weeks.

    Measured: Up to approximately 9 months

  10. Bone Marrow (BM) Blast Complete Remission (MF, myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm (MPN))

    Defined as BM blasts achieving the protocol defined criteria.

    Measured: Up to approximately 9 months

  11. BM Blast Partial Remission (MF, MDS, and MDS/MPN)

    Defined as BM blasts achieving the protocol defined criteria.

    Measured: Up to approximately 9 months

  12. Peripheral Blast Complete Remission (MF, MDS, and MDS/MPN)

    Defined as peripheral blasts achieving the protocol defined criteria.

    Measured: Up to approximately 9 months

  13. Peripheral Blast Partial Remission (MF, MDS, and MDS/MPN)

    Defined as peripheral blast achieving the protocol defined criteria.

    Measured: Up to approximately 9 months

  14. Durable Blast Complete or Partial remission (MF, MDS, and MDS/MPN)

    Defined as achieving the protocol defined criteria.

    Measured: Up to approximately 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2020
  2. Study start23 Feb 2021
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
monotherapy and ruxoltinib combination
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04279847
Sponsor's protocol ID
INCB 57643-103
Other IDs
2023-506145-38-00, 2020-003532-25, 2023
Acronym
LIMBER
Status last verified
Mar 2026
First submitted
18 Feb 2020
Last updated
1 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to patient level data is not available for this study

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing INCB057643 and Ruxolitinib in people with Myelofibrosis and Myelodysplastic Syndrome, run by Incyte Corporation at 48 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, Italy, Japan, Spain, China and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of treatment-emergent adverse events (time frame: Up to approximately 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04279847.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.

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