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

NCT04176198 | Recruiting Phase 1 FDA Drug

• 1 other identifier: BBI-TP-3654-102
• Study Type: interventional
• Target: 240
• Locations: 8 countries
• Sites: 84

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

Outcome Measures

Primary Outcomes (3)

• Determine the incidence of dose-limiting toxicities (DLTs)

  Number of participants with DLTs

  28 days

• Determine the incidence of treatment emergent adverse events

  Number of participants with Treatment Emergent Adverse Events and Serious Adverse Events

  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)

  Number of participants with ≥ 35% spleen volume reduction (SVR35)

  From start of treatment to end of study

Secondary Outcomes (9)

• Number of participants achieving objective response by IWG-MRT response criteria

  From start of treatment to end of study

• Number of participants who have ≥ 25% spleen volume reduction

  Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks therafter during treatment.

• Number of participants with ≥ 50% improvement in total symptom score (TSS50) at week 24

  24 weeks

• Determine the change in Patient Global Impression of Change (PGIC) at week 24 through end of study.

  After 24 weeks of treatment to end of study

• Determine the incidence of QT interval changes

  25 hours

Other Outcomes (6)

• Number of patients with reduction in bone marrow fibrosis

  Every 24 weeks to end of study

• Study potential pharmacodynamic (PD) markers of nuvisertib

  12 months

• Nuvisertib monotherapy: Changes in platelet count over time in patients with baseline platelet count < 100 x 10^9/L

  From start of treatment to end of study

Study Arms (3)

Arm 1: nuvisertib (TP-3654)

EXPERIMENTAL

Drug: Nusivertib

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

EXPERIMENTAL

Drug: Nusivertib; Drug: Ruxolitinib

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

EXPERIMENTAL

Drug: Nusivertib; Drug: Momelotinib

Interventions

Nusivertib DRUG

Oral PIM Inhibitor

Also known as: TP-3654

Arm 1: nuvisertib (TP-3654); Arm 2: nuvisertib (TP-3654) added on to ruxolitinib; Arm 3: nuvisertib (TP-3654) in combination with momelotinib

Ruxolitinib DRUG

Oral JAK inhibitor

Also known as: Jakafi

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

Momelotinib DRUG

Oral JAK inhibitor

Also known as: Ojjaara

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (84)

University of Alabama

Birmingham, Alabama, 35294, United States

RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

Hoag Family Cancer Institute

Newport Beach, California, 92663, United States

RECRUITING

Blood Cancer Center

Denver, Colorado, 80218, United States

RECRUITING

Yale School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

University of Florida Health Shands Cancer Hospital

Gainesville, Florida, 32608, United States

COMPLETED

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Baptist Health - Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Maryland

Baltimore, Maryland, 21201, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

COMPLETED

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

Montefiore Cancer Center

The Bronx, New York, 10461, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Tri-Star Centennial Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77054, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

University of Washington - Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

RECRUITING

Eastern Health Box Hill Hospital

Box Hill, Victoria, Australia

RECRUITING

Monash University

Clayton, Victoria, Australia

RECRUITING

Peter McCallum Center

Melbourne, Victoria, Australia

RECRUITING

Epworth Healthcare

Richmond, Victoria, Australia

RECRUITING

Icon Cancer Centre (Ashford Cancer Centre Research)

Adelaide, Australia

RECRUITING

University Hospitals Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

ZNA Cadix

Antwerp, 2020, Belgium

RECRUITING

ZNA Middelheim

Antwerp, 2030, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

CHU de Liege

Liège, 4000, Belgium

RECRUITING

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

St. Paul's Hospital Hematology/Oncology Research

Vancouver, British Columbia, V6T 1Z3, Canada

RECRUITING

University of British Columbia

Vancouver, British Columbia, V6T 1Z3, Canada

RECRUITING

Juravinski Cancer Center

Hamilton, Ontario, L8V 5C2, Canada

NOT YET RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Centre Hospitalier Universitaire D'Amiens

Amiens, 80054, France

RECRUITING

CHU Angers

Angers, 9000, France

RECRUITING

Centre Hospitalier Lyon Sud

Lyon, 69495, France

RECRUITING

Hospitalier Universitaire (CHU) de Nice - Hopital de l'Archet

Nice, 06200, France

RECRUITING

Institut de cancerologie du Gard

Nîmes, 30029, France

RECRUITING

Institut de cancerologie du Gard

Nîmes, France

RECRUITING

Hospital Saint Louis

Paris, 75010, France

RECRUITING

University Hospital of Poitiers

Poitiers, 86021, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo

Alessandria, 15121, Italy

RECRUITING

Istituto Nazionale Tumori, IRCCS Centro di Riferimento Oncologico di Aviano

Aviano, 33081, Italy

RECRUITING

IRCCS Azienda Ospedaliero -Universitaria Di Bologna - Dipartimento Malattie Oncologiche ed Ematologiche - UO Ematologia

Bologna, 40138, Italy

RECRUITING

ASST - Spedali Civili di Brescia

Brescia, Italy

RECRUITING

IRCCS istituto Romagnolo per lo studio dei tumori "Dino Amadori"

Meldola, 47014, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

Azienda Ospedaliera Universitaria Citta' Della Salute E della Scienza di Torino

Torino, 10126, Italy

RECRUITING

Aichi Medical University Hospital

Aichi, Japan

RECRUITING

Aomori Prefectural Central Hospital

Aomori, Japan

RECRUITING

National Cancer Center Hospital East

Chiba, Japan

RECRUITING

Kyushu University Hospital

Fukuoka, Japan

RECRUITING

Hokkaido University Hospital

Hokkaido, Japan

RECRUITING

Shonan Kamakura General Hospital

Kamakura, 247-8533, Japan

RECRUITING

University of Miyazaki Hospital

Miyazaki, Japan

RECRUITING

Okayama University Hospital

Okayama, Japan

RECRUITING

The University of Osaka Hospital

Osaka, Japan

RECRUITING

Saitama Medical Center

Saitama, Japan

RECRUITING

Tohoku University Hospital

Sendai, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, Japan

COMPLETED

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

RECRUITING

Juntendo University Hospital

Tokyo, Japan

RECRUITING

Mie University Hospital

Tsu, Japan

RECRUITING

Lincoln County Hospital

Lincoln, United Kingdom

RECRUITING

United Lincolnshire Hospitals NHS Trust - Pilgrim Hospital

Lincoln, United Kingdom

RECRUITING

University College London Hospital's NHS foundation Trust

London, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation

Oxford, United Kingdom

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

TP 3654; ruxolitinib; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Reyna Bishop

CONTACT

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

Jordan Simpson

CONTACT

jordan.simpson@us.sumitomo-pharma.com

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: November 8, 2019
• First Posted: November 25, 2019
• Study Start: December 16, 2019
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

GB (4); FR (9); CA (6); AU (6); US (32); IT (7); BE (5); JP (15)