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

NCT ID: NCT04279847

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-23
• Study Completion Date: 2026-12-30

Brief 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.

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); ET (Essential Thrombocythemia)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 : INCB057643 Monotherapy

INCB057643 dose escalation and dose expansion

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

INCB057643 dose escalation and dose expansion.

Part 2 : INCB057643 Combination with Ruxolitinib

Combination arm in dose escalation and dose expansion

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

INCB057643 dose escalation and dose expansion.

Ruxolitinib

Intervention Type: DRUG

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

Interventions

INCB057643

INCB057643 dose escalation and dose expansion.

Intervention Type: DRUG

Ruxolitinib

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

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama At Birmingham

Birmingham, Alabama, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Emory University-Winship Cancer Institute

Atlanta, Georgia, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Washington University School of Medicine

St Louis, Missouri, United States

Rutgers Cancer Institute of Nj

New Brunswick, New Jersey, United States

Nyu Langone Health - Long Island Hospital

Mineola, New York, United States

Nyu Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, United States

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States

Md Anderson Cancer Center

Houston, Texas, United States

Oncology Consultants

Houston, Texas, United States

Huntsman Cancer Institute At University of Utah

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Princess Margaret Cancer Center

Toronto, Ontario, Canada

McGill University Jewish General Hospital

Montreal, Quebec, Canada

St Paul'S Hospital

Vancouver, , Canada

Peking Union Medical College Hospital

Beijing, , China

Nanfang Hospital_Southern Medical University

Guangzhou, , China

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

Hangzhou, , China

Henan Cancer Hostipal

Zhengzhou, , China

Helsinki University Central Hospital

Helsinki, , Finland

Aou Policlinico S. Orsola-Malpighi

Bologna, , Italy

Azienda Ospedaliero-Universitaria Careggi (Aouc)

Florence, , Italy

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori

Meldola, , Italy

Fondazione Irccs Ca Granda Ospedale Maggiore

Milan, , Italy

Azienda Ospedaliero Universitaria San Luigi Gonzaga Di Orbassano

Orbassano, , Italy

Centro Ricerche Cliniche Di Verona

Verona, , Italy

Fujita Health University Hospital

Aichi, , Japan

Chiba University Hospital

Chiba, , Japan

National Cancer Center Hospital East

Chiba, , Japan

University of Yamanashi Hospital

Chūō, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Kumamoto Shinto General Hospital

Kumamoto, , Japan

Hospital Universitari Germans Trias I Pujol

Badalona, , Spain

Hospital Universitario de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Virgen de La Arrixaca

Murcia, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

United Lincolnshire Hospitals

Boston, , United Kingdom

Lincoln County Hospital

Lincoln, , United Kingdom

The Christie Nhs Foundation Trust Uk

Manchester, , United Kingdom

University of Oxford

Oxford, , United Kingdom

Countries

United States; Canada; China; Finland; Italy; Japan; Spain; United Kingdom

Related Links

https://www.incyteclinicaltrials.com/limber/

Related Info

https://www.incyteclinicaltrials.com/study/?id=INCB%2057643-103&SearchTerm=INCB%2057643-103&Latitude=&Longitude=&LocationName=&conditions=&Status=&phases=&AgeRanges=&gender=&StudyTypes=&AttachmentTypes=&MileRadius=100&PageIndex=0&PageSize=10&SortField=&SortOrder=&hasResults=

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

Other Identifiers

2023-506145-38-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-003532-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 57643-103

Identifier Type: -

Identifier Source: org_study_id