Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms
- Conditions
- Myelodysplastic/Myeloproliferative Neoplasm Overlap SyndromeMyelodysplastic SyndromeMyeloproliferative NeoplasmRelapsed or Refractory Primary MyelofibrosisSecondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis)ET (Essential Thrombocythemia)Myelofibrosis
- Interventions
- Registration Number
- NCT04279847
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 231
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Age 18 years and older at the time of signing the informed consent.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Prior receipt of a BET inhibitor.
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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.
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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.
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Concurrent anticancer therapy other than the therapies being tested in this study.
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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.
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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.
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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.
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Active bacterial, fungal, parasitic, or viral infection that requires therapy.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 : INCB057643 Combination with Ruxolitinib Ruxolitinib Combination arm in dose escalation and dose expansion Part 1 : INCB057643 Monotherapy INCB057643 INCB057643 dose escalation and dose expansion Part 2 : INCB057643 Combination with Ruxolitinib INCB057643 Combination arm in dose escalation and dose expansion
- Primary Outcome Measures
Name Time Method Number of treatment-emergent adverse events Up to approximately 9 months 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.
- Secondary Outcome Measures
Name Time Method Symptom Response Rate (MF or ET) Week 24 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.
Duration of Anemia Response (MF only) Up to approximately 9 months 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.
Duration of a Spleen Volume Response from baseline (MF only) Up to approximately 9 months 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.
Duration of platelet count reduction or White Blood Cell (WBC) count reduction (ET only) Up to approximately 9 months Defined as platelet count reduction or WBC count reduction lasting ≥ 12 weeks.
Anemia Response (MF only) Up to approximately 9 months 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.
Changes in hemoglobin value from baseline (MF only) Up to approximately 9 months Defined as the mean change from baseline in the hemoglobin value over 12-week treatment periods.
Bone Marrow (BM) Blast Complete Remission (MF, myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm (MPN)) Up to approximately 9 months Defined as BM blasts achieving the protocol defined criteria.
Spleen Volume Response Week 24 Defined as achieving a protocol defined reduction at Week 24 relative to baseline as measured by MRI or CT scan.
Red Blood Cell (RBC) Transfusion Burden (MF only) Up to approximately 9 months Defined as the average number of RBC units per participant-month through Weeks 12, 24, and 48.
Overall response (ET only) Up to approximately 9 months Defined as proportion of participants with complete response or partial response and hematological improvement/response as per definition for ET.
BM Blast Partial Remission (MF, MDS, and MDS/MPN) Up to approximately 9 months Defined as BM blasts achieving the protocol defined criteria.
Peripheral Blast Complete Remission (MF, MDS, and MDS/MPN) Up to approximately 9 months Defined as peripheral blasts achieving the protocol defined criteria.
Peripheral Blast Partial Remission (MF, MDS, and MDS/MPN) Up to approximately 9 months Defined as peripheral blast achieving the protocol defined criteria.
Durable Blast Complete or Partial remission (MF, MDS, and MDS/MPN) Up to approximately 9 months Defined as achieving the protocol defined criteria.
Trial Locations
- Locations (52)
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
🇺🇸Saint Louis, Missouri, United States
Rutgers Cancer Institute of Nj
🇺🇸New Brunswick, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, 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
University of Alabama At Birmingham
🇺🇸Birmingham, Alabama, 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
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, 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)
🇮🇹Firenze, Italy
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
🇮🇹Meldola, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore
🇮🇹Milan, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
🇮🇹Orbassano, Italy
Azienda Policlinico Umberto 1 Universita Sapienza Di Roma
🇮🇹Rome, 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
🇯🇵Chuo, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Kumamoto Shinto General Hospital
🇯🇵Kumamoto, Japan
Radboud University Nijmegen Medical Center
🇳🇱Nijmegen, Netherlands
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