Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms
LIMBER
A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms
3 other identifiers
interventional
140
8 countries
48
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2021
Longer than P75 for phase_1
48 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 18, 2020
CompletedFirst Posted
Study publicly available on registry
February 21, 2020
CompletedStudy Start
First participant enrolled
February 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2027
April 1, 2026
March 1, 2026
6.2 years
February 18, 2020
March 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
Up to approximately 9 months
Secondary Outcomes (14)
Spleen Volume Response
Week 24
Duration of a Spleen Volume Response from baseline (MF only)
Up to approximately 9 months
Symptom Response Rate (MF or ET)
Week 24
Anemia Response (MF only)
Up to approximately 9 months
Duration of Anemia Response (MF only)
Up to approximately 9 months
- +9 more secondary outcomes
Study Arms (2)
Part 1 : INCB057643 Monotherapy
EXPERIMENTALINCB057643 dose escalation and dose expansion
Part 2 : INCB057643 Combination with Ruxolitinib
EXPERIMENTALCombination arm in dose escalation and dose expansion
Interventions
Ruxolitinib will be administered twice a day using the dose described for each Cohort in the protocol for Part 2.
INCB057643 dose escalation and dose expansion.
Eligibility Criteria
You may qualify if:
- 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.
- +6 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (48)
University of Alabama At Birmingham
Birmingham, Alabama, 35294, United States
University of Colorado Cancer Center
Aurora, Colorado, 80045, United States
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Emory University-Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Rutgers Cancer Institute of Nj
New Brunswick, New Jersey, 08901, United States
Nyu Langone Health - Long Island Hospital
Mineola, New York, 11501, United States
Nyu Langone Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016, United States
Weill Medical College of Cornell University
New York, New York, 10021, United States
University of North Carolina At Chapel Hill
Chapel Hill, North Carolina, 27514, United States
University of Cincinnati Cancer Institute
Cincinnati, Ohio, 45267, United States
Ohio State University
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, 75246, United States
Md Anderson Cancer Center
Houston, Texas, 77030, United States
Oncology Consultants
Houston, Texas, 77030, United States
Huntsman Cancer Institute At University of Utah
Salt Lake City, Utah, 84112, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9, Canada
McGill University Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
St Paul'S Hospital
Vancouver, V6Z2A5, Canada
Peking Union Medical College Hospital
Beijing, 100730, China
Nanfang Hospital_Southern Medical University
Guangzhou, 510515, China
The First Affiliated Hospital, Zhejiang University School of Medicine (Fahzu)
Hangzhou, 310003, China
Henan Cancer Hostipal
Zhengzhou, 450003, China
Helsinki University Central Hospital
Helsinki, 00029, Finland
Aou Policlinico S. Orsola-Malpighi
Bologna, 40138, Italy
Azienda Ospedaliero-Universitaria Careggi (Aouc)
Florence, 50134, Italy
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
Meldola, 47014, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore
Milan, 20122, Italy
Azienda Ospedaliero Universitaria San Luigi Gonzaga Di Orbassano
Orbassano, 10043, Italy
Centro Ricerche Cliniche Di Verona
Verona, 37134, Italy
Fujita Health University Hospital
Aichi, 470-1192, Japan
Chiba University Hospital
Chiba, 260-8677, Japan
National Cancer Center Hospital East
Chiba, 277-8577, Japan
University of Yamanashi Hospital
Chūō, 409-3898, Japan
Kyushu University Hospital
Fukuoka, Japan
Kumamoto Shinto General Hospital
Kumamoto, 862-8655, Japan
Hospital Universitari Germans Trias I Pujol
Badalona, 08916, Spain
Hospital Universitario de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria, 35010, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario Virgen de La Arrixaca
Murcia, 30120, Spain
Hospital Clinico Universitario de Salamanca
Salamanca, 37007, Spain
United Lincolnshire Hospitals
Boston, PE21 9QS, United Kingdom
Lincoln County Hospital
Lincoln, LN2 5QY, United Kingdom
The Christie Nhs Foundation Trust Uk
Manchester, M20 4BX, United Kingdom
University of Oxford
Oxford, OX3 7LE, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 18, 2020
First Posted
February 21, 2020
Study Start
February 23, 2021
Primary Completion (Estimated)
April 30, 2027
Study Completion (Estimated)
April 30, 2027
Last Updated
April 1, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share
Access to patient level data is not available for this study