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.
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
- Conditions the study is for
- Myelofibrosis, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome
- 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
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
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
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
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
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
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
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
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.
- Conditions
- Myelofibrosis, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome, Myeloproliferative Neoplasm, Relapsed or Refractory Primary Myelofibrosis, Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis)
- 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 group | Role | What they receive |
|---|---|---|
| Part 1 : INCB057643 Monotherapy | Experimental | INCB057643 dose escalation and dose expansion Receives: Drug: INCB057643 |
| Part 2 : INCB057643 Combination with Ruxolitinib | Experimental | Combination 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.
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)
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
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
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
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
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
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
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
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
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
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
BM Blast Partial Remission (MF, MDS, and MDS/MPN)
Defined as BM blasts achieving the protocol defined criteria.
Measured: Up to approximately 9 months
Peripheral Blast Complete Remission (MF, MDS, and MDS/MPN)
Defined as peripheral blasts achieving the protocol defined criteria.
Measured: Up to approximately 9 months
Peripheral Blast Partial Remission (MF, MDS, and MDS/MPN)
Defined as peripheral blast achieving the protocol defined criteria.
Measured: Up to approximately 9 months
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.
- First posted21 Feb 2020
- Study start23 Feb 2021
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
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