A Study of Nuvisertib for Myelofibrosis
This study is testing a new oral medication called nuvisertib (TP-3654) for people with myelofibrosis (a bone marrow disorder where scar tissue replaces normal blood-producing cells). Researchers want to see how safe nuvisertib is, how well your body handles it, and if it can help shrink an enlarged spleen. You might be able to join if you have intermediate or high-risk myelofibrosis and have already been treated with a JAK inhibitor (like ruxolitinib or momelotinib) but it didn't work well, or you couldn't take it. The study is also looking at nuvisertib in combination with ruxolitinib for those who are already taking ruxolitinib but aren't getting the full benefit. The study plans to enroll 240 participants, but its current status is unclear.
- Study design
- This is a Phase 1/2, multicenter, open-label study, meaning you and your doctors will know which treatment you are receiving. It is designed to assess nuvisertib alone or in combination with other drugs.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Researchers will monitor for side effects from the start of treatment until the end of the study. They will also assess spleen size from the start of treatment until the end of the study.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04176198
A Study of Oral Nuvisertib (TP-3654) in Patients With Myelofibrosis
Recruiting
PHASE1Ages 18+InterventionalTreatmentSumitomo Pharma America, Inc.
~240 participants
Updated 2026-08-03 on ClinicalTrials.gov
What's tested:NusivertibRuxolitinibMomelotinib
At a glance
Recruiting sites
85 of 90 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Determine the incidence of dose-limiting toxicities (DLTs)
Measured over 28 days
+2 more outcomes measured
Conditions
Where it's being run
90 sites across 38 statesJapan15
France9
Italy7
New York5
Victoria5
Belgium4
United Kingdom4
California3
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF
Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be treated with JAK inhibitor
Fulfill the following clinical laboratory parameters:
Platelet count ≥ 25 x 10\^9 /L, without assistance of growth factors or platelet transfusions
ANC ≥ 1 x 10\^9/L without assistance of granulocyte growth factors
Peripheral blood blast count \< 5%
ECOG performance status ≤ 1
Life expectancy ≥ 6 months
Adequate renal function
Adequate hepatic function
Adequate coagulation function
Splenomegaly (spleen volume of ≥ 450 cm3 by MRI or CT scan) within 2 weeks prior to Cycle 1 Day 1.
Dose escalation: At least 2 symptoms measurable (score ≥ 1) using the MF-SAF
Dose expansion: At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF
Confirmed pathological diagnosis of PMF or post-PV-MF/post ET- MF and intermediate or high-risk primary or secondary MF
On ruxolitinib treatment for ≥ 6 months, and on a stable dose of ruxolitinib (5 to 25 mg BID) for ≥ 8 weeks prior to the first dose of nuvisertib, but has either lost response or had a suboptimal or plateau in response
Fulfills the following clinical laboratory parameters:
Platelet count ≥ 50 × 10\^9/L (without assistance of growth factors or platelet transfusions)
ANC ≥ 1 × 109/L without assistance of granulocyte growth factors
Peripheral blood blast count \< 5% at screening
Adequate renal function
Adequate hepatic function
Adequate coagulation function
Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1
At least 2 symptoms measurable with each score ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0
ECOG performance status ≤ 1
Life expectancy ≥ 6 months
Confirmed pathological diagnosis of PMF or post-PV-MF/post ET-MF and intermediate or high-risk primary or secondary MF
Previously treated with an approved JAK inhibitor (except momelotinib) for PMF or Post-PV/ET MF for ≥ 12 weeks, or ≥ 4 weeks if JAK inhibitor therapy was complicated by a transfusion requirement of ≥ 4 units of red blood cells in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma
Fulfills the following clinical laboratory parameters:
Anemic, defined as Hb \<10 g/dL or requiring RBC transfusion at baseline
Platelet count ≥ 50 × 109/L (without assistance of growth factors or platelet transfusions)
ANC ≥ 1 × 109/L without assistance of granulocyte growth factors
Peripheral blood blast count \< 5% at screening
Adequate renal function
Adequate hepatic function
Adequate coagulation function
Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1
At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0
ECOG performance status ≤ 1
Life expectancy ≥ 6 months
Exclusion
Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1. Hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or not recovered adequately from from surgery prior to first dose.
Splenic irradiation within 6 months prior to Screening or prior splenectomy.
Prior allogeneic stem cell transplant within the last 6 months.
Eligible for allogeneic bone marrow or stem cell transplantation.
Unresolved Grade ≥ 2 non-hematological toxicity related to prior treatment
History of symptomatic congestive heart failure, or myocardial infarction, or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) \< 45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1.
Corrected QT interval \> 480msec.
Prior or concurrent malignancy that could interfere with the investigational regime.
Known history of chronic liver disease, e.g. portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc.
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic antimicrobial within 1 week prior to Cycle 1 Day 1.
Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
Exhibited allergic reactions or sensitivity to nuvisertib, or similar compound.
Medical condition or GI tract surgery that could impair absorption or result in short bowel syndrome with diarrhea.
Systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 1 week prior to the first dose of study treatment (note: topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding.
Pregnant or breastfeeding
Currently receiving any other investigational agent.
Received previous systemic antineoplastic therapy (other than ruxolitinib) or any other experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1 (Note: Prior treatment with nuvisertib is not allowed. Hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
Received systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 1 week prior to Cycle 1 Day 1 (Note: Topical, inhaled, nasal, and ophthalmic steroids are not prohibited)
Known allergic reactions or sensitivity to nuvisertib, or similar compound.
Splenic irradiation within 6 months prior to Screening or prior splenectomy
Prior allogeneic stem cell transplant within the last 6 months (Note: Patients who have relapsed after 6 months post-transplant and do not have active GVHD are eligible).
Eligible for allogeneic bone marrow or stem cell transplantation (Note: Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible.)
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or have not recovered adequately prior to first dose.
Active, uncontrolled bacterial, viral, or fungal infections, requiring parenteral antimicrobial within 1 week prior to Cycle 1 Day 1
Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
Known history of chronic liver disease (eg, portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc) (Note: Abnormal liver morphology at baseline imaging may require additional testing, as needed).
Unresolved Grade ≥ 2 non-hematological adverse events related to prior treatment (stable Grade 2 conditions may be permitted in consultation with the Sponsor)
History of myocardial infarction or symptomatic congestive heart failure or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; LVEF \<45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1
Corrected QTcF of \> 480 msec
Prior or concurrent malignancy that could interfere with the safety or efficacy assessment of the study intervention
History of a medical condition or GI tract surgery that could impair absorption or could result in short bowel syndrome with diarrhea
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding
Pregnant or breastfeeding
Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1 (Notes: Prior treatment with momelotinib or nuvisertib is not allowed; in patients with ongoing JAK inhibitor therapy, ie, ruxolitinib, at screening, JAK inhibitor therapy must be tapered over a period of at least 1 week. Patients on a low dose of ruxolitinib (eg, 5 mg QD) may have a reduced taper period or no taper; hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
Received systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 1 week prior to Cycle 1 Day 1 (Note: Topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
Known allergic reactions or sensitivity to nuvisertib, momelotinib, or any structurally similar drug, or to any component of the formulations of either study intervention
Splenic irradiation within 6 months prior to screening or prior splenectomy
Prior allogenic stem cell transplant within the last 6 months (Note: Patients who have relapsed after 6 months post-transplant and do not have active GVHD are eligible).
Eligible for allogeneic bone marrow or stem cell transplantation (Note: Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible).
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or have not recovered adequately from surgery prior to first dose.
Active, uncontrolled bacterial, viral, or fungal infections, requiring parenteral antimicrobial within 1 week prior to Cycle 1 Day 1
Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
Known history of chronic liver disease (eg, portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc) (Note: Abnormal liver morphology at baseline imaging may require additional testing, as needed)
Unresolved Grade ≥ 2 non-hematological adverse events related to prior treatment (stable Grade 2 conditions may be permitted in consultation with the Sponsor)
Presence of Grade ≥ 2 peripheral neuropathy
History of myocardial infarction or symptomatic congestive heart failure or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; LVEF \< 45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1
Corrected QTcF of \> 480 msec
Prior or concurrent malignancy that could interfere with the safety or efficacy assessment of the study intervention
History of a medical condition or GI tract surgery that could impair absorption or could result in short bowel syndrome with diarrhea
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding
Pregnant or breastfeeding
What this trial measures
- Determine the incidence of dose-limiting toxicities (DLTs)28 days
Number of participants with DLTs
- Determine the incidence of treatment emergent adverse eventsFrom start of treatment to end of study
Number of participants with Treatment Emergent Adverse Events and Serious Adverse Events
- Assess patients for any evidence of preliminary activity by determining the number of patients with ≥ 35% spleen volume reduction (SVR35)From start of treatment to end of study
Number of participants with ≥ 35% spleen volume reduction (SVR35)