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

Phase 1

Recruiting

• Conditions: Myelofibrosis
• Interventions: Drug: Nusivertib; Drug: Momelotinib; Drug: Ruxolitinib

• Registration Number: NCT04176198
• Lead Sponsor: Sumitomo Pharma America, Inc.

Brief Summary

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

Detailed Description

Arm 1 will enroll patients who have been previously treated and failed on a JAK inhibitor or ineligible to receive treatment with a JAK inhibitor.

Arm 2 will enroll patients who are on a stable dose of ruxolitinib, but who have either lost response or had a suboptimal or plateau in response.

Arm 3 will enroll patients who have been previously treated on JAK inhibitor (except momelotinib) that was complicated by anemia, thrombocytopenia or hematoma.

Study Timeline

• Study First Submitted: 2019-11-08
• Study First Submitted QC: 2019-11-22
• Study First Posted: 2019-11-25
• Study Start: 2019-12-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-05-29
• Last Update Posted: 2025-06-04
• Primary Completion: 2027-04-30
• Study Completion: 2030-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: nuvisertib (TP-3654)	Nusivertib	-
Arm 3: nuvisertib (TP-3654) in combination with momelotinib	Nusivertib	-
Arm 3: nuvisertib (TP-3654) in combination with momelotinib	Momelotinib	-
Arm 2: nuvisertib (TP-3654) added on to ruxolitinib	Nusivertib	-
Arm 2: nuvisertib (TP-3654) added on to ruxolitinib	Ruxolitinib	-

Primary Outcome Measures

Name	Time	Method
Determine the incidence of dose-limiting toxicities (DLTs)	28 days	Number of participants with DLTs
Determine the incidence of treatment emergent adverse events	From 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)

Secondary Outcome Measures

Name	Time	Method
Establish the half-life (t½) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib	24 hours	The estimate of time for the nuvisertib concentration or amount to be reduced by half
Establish the Area under the plasma concentration versus time curve (AUC) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib	24 hours	The amount of drug exposure over 24 hours period after administration
Establish the Peak Plasma Concentration (Cmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib	24 hours	The maximum nuvisertib concentration after administration
Number of participants achieving objective response by IWG-MRT response criteria	From start of treatment to end of study	Number of participants achieving complete remission, partial remission, clinical improvement, progressive disease and stable disease.
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 who have ≥ 25% spleen volume reduction compared to baseline
Number of participants with ≥ 50% improvement in total symptom score (TSS50) at week 24	24 weeks	Number of participants who have ≥ 50% total symptom score reduction by MFSAF compared to baseline after 24 weeks of treatment.
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	Change in PGIC score
Determine the incidence of QT interval changes	25 hours	Changes in QT interval and heart rhythm
Establish the Time of Maximum concentration observed (tmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib	24 hours	The time to reach maximum nuvisertib concentration

Trial Locations

Locations (76)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

The University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

City of Hope; 🇺🇸 Duarte, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Hoag Family Cancer Institute; 🇺🇸 Newport Beach, California, United States

Blood Cancer Center; 🇺🇸 Denver, Colorado, United States

Yale School of Medicine; 🇺🇸 New Haven, Connecticut, United States

University of Florida Health Shands Cancer Hospital; 🇺🇸 Gainesville, Florida, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

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