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Evaluating the safety of INCB057643 for patients with myelofibrosis and related conditions

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

Phase 1 Interventional Incyte Corporation · NCT04279847

This study is testing a new drug called INCB057643 to see if it is safe for people with myelofibrosis and related conditions, both on its own and when used with another medication.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment231 (estimated)
Ages18 Years and up
SexAll
SponsorIncyte Corporation Industry-sponsored
Drugs / interventionsruxolitinib
Locations52 sites (Birmingham, Alabama and 51 other locations)
Trial IDNCT04279847 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety and tolerability of INCB057643, both as a standalone treatment and in combination with ruxolitinib, for individuals diagnosed with myelofibrosis and other advanced myeloid neoplasms. Participants must have previously undergone at least one line of therapy and be either refractory, relapsed, or intolerant to their last treatment. The study will involve two parts: one focusing on monotherapy and the other on combination therapy. The goal is to gather preliminary efficacy data alongside safety assessments.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory myelofibrosis or other specified myeloid neoplasms who have received prior therapies.

Not a fit: Patients who have not received prior treatment or those with early-stage disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with myelofibrosis and related conditions who have limited treatment choices.

How similar studies have performed: Other studies have shown promise with similar approaches, particularly in targeting myelofibrosis with novel therapies.

Eligibility criteria

Show full inclusion / exclusion criteria 
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% (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.

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. 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.

Where this trial is running

Birmingham, Alabama and 51 other locations

+2 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions MyelofibrosisMyelodysplastic SyndromeMyelodysplastic/Myeloproliferative Neoplasm Overlap SyndromeMyeloproliferative NeoplasmRelapsed or Refractory Primary MyelofibrosisSecondary MyelofibrosisETmyelodysplastic syndrome
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.