Recruiting

Phase 1

Phase 2

NuvisertibA Study of Oral Nuvisertib (TP-3654) in Patients With Myelofibrosis

Sponsor:

Sumitomo Pharma America, Inc.

Code:

NCT04176198

Conditions

Myelofibrosis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Nusivertib

Ruxolitinib

Momelotinib

Study Details

Brief summary:

This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary MF.

Conditions

Myelofibrosis

Study ID

NCT04176198

Start date

Dec 16, 2019

Status verified date

Jul, 2026

Completion date

Apr 30, 2030

Anticipated

Primary completion date

Apr 30, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Patients must meet all of the following inclusion criteria to be eligible:

Nuvisertib (TP-3654) Monotherapy Arm:

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

Nuvisertib (TP-3654) + Ruxolitinib Arm:

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

Nuvisertib (TP-3654) + Momelotinib Arm

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

Patients meeting any one of these exclusion criteria will be prohibited from participating in this study:

Nuvisertib (TP-3654) Monotherapy Arm:

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.

Nuvisertib (TP-3654) + Ruxolitinib Arm:

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

Nuvisertib (TP-3654) + Momelotinib Arm:

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

Study Design

Enrollment

240 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: nuvisertib (TP-3654)

experimental: Arm 2: nuvisertib (TP-3654) added on to ruxolitinib

experimental: Arm 3: nuvisertib (TP-3654) in combination with momelotinib

Interventions

Nusivertib

Oral PIM Inhibitor

Ruxolitinib

Oral JAK inhibitor

Momelotinib

Oral JAK inhibitor

Primary outcome measure

Determine the incidence of dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]
Determine the incidence of treatment emergent adverse events [ Time Frame: From start of treatment to end of study ]
Assess patients for any evidence of preliminary activity by determining the number of patients with ≥ 35% spleen volume reduction (SVR35) [ Time Frame: From start of treatment to end of study ]

Central Contacts and Locations

Central contacts

Reyna Bishop

617-674-6800 reyna.bishop@us.sumitomo-pharma.com

Jordan Simpson

jordan.simpson@us.sumitomo-pharma.com

Locations

University of Alabama

Recruiting

Birmingham, Alabama, United States, 35294

Contacts

Tiffany Hill

205-934-9591

The University of Arizona Cancer Center

Recruiting

Tucson, Arizona, United States, 85724

Contacts

Audrey Johnson

520-694-9084 audieejayy@arizona.edu

City of Hope

Recruiting

Duarte, California, United States, 91010

Contacts

Michelle Velasquez

626-218-3524 mvelaszuez@coh.org

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

Shirley Sian

323-865-0456 sian_s@med.usc.edu

Hoag Family Cancer Institute

Recruiting

Newport Beach, California, United States, 92663

Contacts

Patrice Jones

949-764-5501 patrice.jones@hoag.org

Blood Cancer Center

Recruiting

Denver, Colorado, United States, 80218

Contacts

Brooke Rhodes

Brookerhodes@sarahcannon.com

Yale School of Medicine

Recruiting

New Haven, Connecticut, United States, 06510

Contacts

Farah Fasihuddin

203-494-4610 farah.fasihuddin@yale.edu

University of Miami

Recruiting

Miami, Florida, United States, 33136

Contacts

Alessia Zoso

305-243-0327 azoso@miami.edu

Baptist Health - Miami Cancer Institute

Recruiting

Miami, Florida, United States, 33176

Contacts

Firas El Chaer, MD

786-596-2000 firas.elchaer@baptisthealth.net

Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Suzanne Scott

404-778-4334 suzanne.e.scott@emory.edu

University of Chicago

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Howie Weiner

HWeiner@bsd.uchicago.edu

University of Maryland

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Maria Baer, MD

410-328-8708 mbaer@umm.edu

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Gabriela Hobbs, MD

ghobbs@mgb.org

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Kelsey Bolin

734-936-2193 kntillma@med.umich.edu

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Naveen Premnath, MD

premn007@umn.edu

Washington University of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Nicole Gaudin

314-747-7960 nrgaudin@wustl.edu

John Theurer Cancer Center at Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601

Contacts

Parita Patel

551-996-5900 parita.patel@hmhn.org

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Contacts

Gabriela Bello

gabriela.bello@mssm.edu

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Tamanna Haque, MD

haquet1@mskcc.org

Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Contacts

Penina Steward

212-746-1858 pes4006@med.cornell.edu

Montefiore Cancer Center

Recruiting

The Bronx, New York, United States, 10461

Contacts

Olivia Orellano

oorellano@montefiore.org

Duke Cancer Institute

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Ben Dosan

benjamin.dosan@duke.edu

Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Molly Brandenburg

614-366-7951 Molly.Brandenburg@osumc.edu

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Contacts

Jared Hortman

hortman@musc.edu

Tri-Star Centennial Medical Center

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Brooke Rhodes

brooke.rhodes@sarahcannon.com

Vanderbilt University

Recruiting

Nashville, Tennessee, United States, 37232

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77054

Contacts

Kurt Schroeder

713-745-2232 kdschroe@mdanderson.org

Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Nicole Fisher

801-587-7000 nicole.fisher@hci.utah.edu

University of Virginia Cancer Center

Recruiting

Charlottesville, Virginia, United States, 22903

Contacts

Avani Hopkins

434-243-8108 AJH7JQE@uvahealth.org

University of Washington - Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Anna Halpern

halpern2@uw.edu

University of Calgary

Recruiting

Calgary, Alberta, Canada, T2N 1N4

Contacts

Sonia Cerquozzi

sonia.cerquozzi@albertahealthservices.ca

St. Paul's Hospital Hematology/Oncology Research

Recruiting

Vancouver, British Columbia, Canada, V6T 1Z3

Contacts

Kelsi Sorensen

604-682-2344 ksorensen1@providencehealth.bc

University of British Columbia

Recruiting

Vancouver, British Columbia, Canada, V6T 1Z3

Princess Margaret Cancer Center

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Vikas Gupta

vikas.gupta@uhn.ca

Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

More Information

Sponsor

Sumitomo Pharma America, Inc.

Last update posted

Aug 3, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Sumitomo Pharma America, Inc. on 2026-08-03.