Actively Recruiting
A Phase 1/2, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral Nuvisertib (TP-3654) in Patients With Intermediate or High-Risk Primary or Secondary Myelofibrosis
Led by Sumitomo Pharma America, Inc. · Updated on 2026-05-01
240
Participants Needed
84
Research Sites
156 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating oral nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary myelofibrosis who have previously been treated with JAK inhibitors. This Phase 1/2, multicenter, dose-escalation, open-label study aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of nuvisertib, including its effects when given alone or in combination with other therapies. The trial includes patients who have failed or are ineligible for JAK inhibitors, those with suboptimal response to ruxolitinib, and those treated with other JAK inhibitors except momelotinib. The study has three arms: Arm 1 involves nuvisertib monotherapy for patients intolerant or resistant to JAK inhibitors; Arm 2 adds nuvisertib to stable doses of ruxolitinib in patients with lost or suboptimal response; Arm 3 combines nuvisertib with momelotinib in patients previously treated with JAK inhibitors other than momelotinib. Dosing will escalate to determine safety levels, and patients must show measurable symptoms and splenomegaly. Treatments are oral and given according to assigned arms. Participants will be closely monitored through clinical assessments, laboratory tests, and imaging to measure spleen volume reduction and symptom improvement. Safety is tracked by documenting dose-limiting toxicities and treatment-emergent adverse events over time. Pharmacokinetic parameters such as drug concentration and half-life will be evaluated. The study duration varies per participant, with ongoing assessments for efficacy and safety throughout the treatment period and follow-up.
CONDITIONS
Brief Title
A Study of Oral Nuvisertib (TP-3654) in Patients With Myelofibrosis
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmed pathological diagnosis of primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate or high risk
- Previously treated with JAK inhibitor(s) and intolerant, resistant, refractory, lost response, or ineligible for JAK inhibitor treatment (for monotherapy arm)
- On ruxolitinib treatment for at least 6 months with stable dose for at least 8 weeks but with lost or suboptimal response (for combination with ruxolitinib arm)
- Previously treated with an approved JAK inhibitor (except momelotinib) for at least 12 weeks or 4 weeks with complications (for combination with momelotinib arm)
- Platelet count and ANC meeting specified minimum levels without growth factor support
- Peripheral blood blast count less than 5%
- ECOG performance status of 0 or 1
- Life expectancy of at least 6 months
- Adequate renal, hepatic, and coagulation function
- Presence of splenomegaly with spleen volume of at least 450 cm3 by MRI or CT scan within 2 weeks prior to treatment start
- At least two measurable symptoms with scores meeting specific thresholds on the Myelofibrosis Symptom Assessment Form
You will not qualify if you...
- Recent systemic antineoplastic or experimental therapy within 2 weeks or 5 half-lives prior to treatment
- Major surgery within 4 weeks prior to treatment or incomplete recovery from surgery
- Splenic irradiation within 6 months or prior splenectomy
- Prior allogeneic stem cell transplant within last 6 months
- Eligibility for allogeneic bone marrow or stem cell transplantation
- Unresolved Grade 2 or higher non-hematological toxicity from prior treatment
- Recent history of severe heart conditions or low left ventricular ejection fraction
- Corrected QT interval greater than 480 msec
- Prior or concurrent malignancy interfering with study treatment
- Known chronic liver disease or abnormal liver conditions
- Active, uncontrolled infections requiring treatment within 1 week prior to treatment
- Chronic active or acute viral hepatitis A, B, or C
- Known allergy or sensitivity to nuvisertib or similar compounds
- Medical conditions or surgeries affecting drug absorption or causing severe diarrhea
- Systemic steroid therapy above specified doses within 1 week prior to treatment
- Significant anemia due to specific causes
- Pregnant or breastfeeding
- Current treatment with other investigational agents
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - From start of treatment until discontinuation
Participants receive oral Nuvisertib either alone or in combination with other medications to treat myelofibrosis.
Visits every 12 weeks through approximately 1 year, then every 24 weeks during treatment
Duration - Until study completion
Participants are monitored for safety and treatment effects after stopping the study drug.
Visits as needed after treatment ends
Trial Site Locations
Total: 84 locations
1
University of Alabama
Birmingham, Alabama, United States, 35294
Actively Recruiting
2
The University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
Actively Recruiting
3
City of Hope
Duarte, California, United States, 91010
Actively Recruiting
4
University of Southern California
Los Angeles, California, United States, 90033
Actively Recruiting
5
Hoag Family Cancer Institute
Newport Beach, California, United States, 92663
Actively Recruiting
6
Blood Cancer Center
Denver, Colorado, United States, 80218
Actively Recruiting
7
Yale School of Medicine
New Haven, Connecticut, United States, 06510
Actively Recruiting
8
University of Florida Health Shands Cancer Hospital
Gainesville, Florida, United States, 32608
Completed
9
University of Miami
Miami, Florida, United States, 33136
Actively Recruiting
10
Baptist Health - Miami Cancer Institute
Miami, Florida, United States, 33176
Actively Recruiting
11
Emory University
Atlanta, Georgia, United States, 30322
Actively Recruiting
12
University of Chicago
Chicago, Illinois, United States, 60637
Actively Recruiting
13
University of Maryland
Baltimore, Maryland, United States, 21201
Actively Recruiting
14
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Actively Recruiting
15
University of Michigan
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
16
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Actively Recruiting
17
Washington University of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
18
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Actively Recruiting
19
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States, 14263
Completed
20
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Actively Recruiting
21
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
22
Weill Cornell Medical Center
New York, New York, United States, 10065
Actively Recruiting
23
Montefiore Cancer Center
The Bronx, New York, United States, 10461
Actively Recruiting
24
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Actively Recruiting
25
Ohio State University
Columbus, Ohio, United States, 43210
Actively Recruiting
26
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Actively Recruiting
27
Tri-Star Centennial Medical Center
Nashville, Tennessee, United States, 37203
Actively Recruiting
28
Vanderbilt University
Nashville, Tennessee, United States, 37232
Actively Recruiting
29
MD Anderson Cancer Center
Houston, Texas, United States, 77054
Actively Recruiting
30
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Actively Recruiting
31
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22903
Actively Recruiting
32
University of Washington - Fred Hutchinson Cancer Center
Seattle, Washington, United States, 98109
Actively Recruiting
33
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Actively Recruiting
34
Eastern Health Box Hill Hospital
Box Hill, Victoria, Australia
Actively Recruiting
35
Monash University
Clayton, Victoria, Australia
Actively Recruiting
36
Peter McCallum Center
Melbourne, Victoria, Australia
Actively Recruiting
37
Epworth Healthcare
Richmond, Victoria, Australia
Actively Recruiting
38
Icon Cancer Centre (Ashford Cancer Centre Research)
Adelaide, Australia
Actively Recruiting
39
University Hospitals Leuven
Leuven, Vlaams-Brabant, Belgium, 3000
Actively Recruiting
40
ZNA Cadix
Antwerp, Belgium, 2020
Actively Recruiting
41
ZNA Middelheim
Antwerp, Belgium, 2030
Actively Recruiting
42
Universitair Ziekenhuis Gent
Ghent, Belgium, 9000
Actively Recruiting
43
CHU de Liege
Liège, Belgium, 4000
Actively Recruiting
44
University of Calgary
Calgary, Alberta, Canada, T2N 1N4
Actively Recruiting
45
St. Paul's Hospital Hematology/Oncology Research
Vancouver, British Columbia, Canada, V6T 1Z3
Actively Recruiting
46
University of British Columbia
Vancouver, British Columbia, Canada, V6T 1Z3
Actively Recruiting
47
Juravinski Cancer Center
Hamilton, Ontario, Canada, L8V 5C2
Not Yet Recruiting
48
Princess Margaret Cancer Center
Toronto, Ontario, Canada, M5G 2M9
Actively Recruiting
49
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Actively Recruiting
50
Centre Hospitalier Universitaire D'Amiens
Amiens, France, 80054
Actively Recruiting
51
CHU Angers
Angers, France, 9000
Actively Recruiting
52
Centre Hospitalier Lyon Sud
Lyon, France, 69495
Actively Recruiting
53
Hospitalier Universitaire (CHU) de Nice - Hopital de l'Archet
Nice, France, 06200
Actively Recruiting
54
Institut de cancerologie du Gard
Nîmes, France, 30029
Actively Recruiting
55
Institut de cancerologie du Gard
Nîmes, France
Actively Recruiting
56
Hospital Saint Louis
Paris, France, 75010
Actively Recruiting
57
University Hospital of Poitiers
Poitiers, France, 86021
Actively Recruiting
58
Institut Gustave Roussy
Villejuif, France, 94805
Actively Recruiting
59
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy, 15121
Actively Recruiting
60
Istituto Nazionale Tumori, IRCCS Centro di Riferimento Oncologico di Aviano
Aviano, Italy, 33081
Actively Recruiting
61
IRCCS Azienda Ospedaliero -Universitaria Di Bologna - Dipartimento Malattie Oncologiche ed Ematologiche - UO Ematologia
Bologna, Italy, 40138
Actively Recruiting
62
ASST - Spedali Civili di Brescia
Brescia, Italy
Actively Recruiting
63
IRCCS istituto Romagnolo per lo studio dei tumori "Dino Amadori"
Meldola, Italy, 47014
Actively Recruiting
64
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Italy, 20122
Actively Recruiting
65
Azienda Ospedaliera Universitaria Citta' Della Salute E della Scienza di Torino
Torino, Italy, 10126
Actively Recruiting
66
Aichi Medical University Hospital
Aichi, Japan
Actively Recruiting
67
Aomori Prefectural Central Hospital
Aomori, Japan
Actively Recruiting
68
National Cancer Center Hospital East
Chiba, Japan
Actively Recruiting
69
Kyushu University Hospital
Fukuoka, Japan
Actively Recruiting
70
Hokkaido University Hospital
Hokkaido, Japan
Actively Recruiting
71
Shonan Kamakura General Hospital
Kamakura, Japan, 247-8533
Actively Recruiting
72
University of Miyazaki Hospital
Miyazaki, Japan
Actively Recruiting
73
Okayama University Hospital
Okayama, Japan
Actively Recruiting
74
The University of Osaka Hospital
Osaka, Japan
Actively Recruiting
75
Saitama Medical Center
Saitama, Japan
Actively Recruiting
76
Tohoku University Hospital
Sendai, Japan
Actively Recruiting
77
Shizuoka Cancer Center
Shizuoka, Japan
Completed
78
Tokyo Medical University Hospital
Tokyo, Japan, 160-0023
Actively Recruiting
79
Juntendo University Hospital
Tokyo, Japan
Actively Recruiting
80
Mie University Hospital
Tsu, Japan
Actively Recruiting
81
Lincoln County Hospital
Lincoln, United Kingdom
Actively Recruiting
82
United Lincolnshire Hospitals NHS Trust - Pilgrim Hospital
Lincoln, United Kingdom
Actively Recruiting
83
University College London Hospital's NHS foundation Trust
London, United Kingdom
Actively Recruiting
84
Oxford University Hospitals NHS Foundation
Oxford, United Kingdom
Actively Recruiting
Research Team
R
Reyna Bishop
J
Jordan Simpson
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here