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

Intermediate or High-risk Primary or Secondary Myelofibrosis

Nuvisertib Monotherapy (Arm 1) - Phase 1: Dose-limiting toxicity (DLT) at escalated doses of Nuvisertib., Nuvisertib Monotherapy (Arm 1) - Phase 1: Adverse events (AEs) as characterized by type, frequency, severity, seriousness, and relationship to study drugs. (Note: This endopoint is secondary in Phase 2), Nuvisertib Monotherapy (Arm 1) - Phase 2: Spleen volume response: ≥35% spleen volume reduction (SVR35) at any time., Nuvisertib + Momelotinib (Arm 3) – Phase 1: Dose-limiting toxicity (DLT) at escalated doses of Nuvisertib when administered in combination with momelotinib., Nuvisertib + Momelotinib (Arm 3) – Phase 1: Adverse events (AEs) as characterized by type, frequency, severity, seriousness, and relationship to study drugs. [Note: This endpoint is secondary in Phase 2], Nuvisertib + Momelotinib (Arm 3) – Phase 2: Spleen volume response: ≥35% spleen volume reduction (SVR35) at any time.

Nuvisertib Monotherapy (Arm 1) - Phase 1 and 2: Spleen volume response: - ≥ 25% spleen volume reduction [SVR25] at any time; - Duration of spleen volume response., Nuvisertib Monotherapy (Arm 1) - Phase 1 and 2: Total symptom score response assessed by MFSAF v4.0; - ≥ 50% improvement in total symptom score (TSS50) at Week 24; - Duration of TSS50 over time during the study; - Absolute TSS change from baseline at Week 24., Nuvisertib Monotherapy (Arm 1) - Phase 1 and 2: Patient Global Impression of Change (PGIC) at Week 24 and at any time., Nuvisertib Monotherapy (Arm 1) - Phase 1 and 2: Response evaluation per the revised IWG-MRT criteria: Complete remission (CR), partial remission (PR), clinical improvement (CI), stable disease (SD), and progressive disease (PD)., Nuvisertib Monotherapy (Arm 1) - Phase 1 and 2: QT interval changes., Nuvisertib Monotherapy (Arm 1) - Phase 1 and 2: PK parameters of Nuvisertib: Cmax, tmax, AUC, t½, and others as data permits., Nuvisertib + Momelotinib (Arm 3) – Phase 1 and 2: Spleen volume response: - ≥25% spleen volume reduction [SVR25] at any time; - Duration of spleen volume response., Nuvisertib + Momelotinib (Arm 3) – Phase 1 and 2: Total symptom score response assessed by MFSAF v4.0: - ≥ 50% improvement in total symptom score (TSS50) at Week 24; - Duration of TSS50 over time during the study; - Absolute TSS change from baseline at Week 24., Nuvisertib + Momelotinib (Arm 3) – Phase 1 and 2: Patient Global Impression of Change (PGIC) at Week 24 and at any time., Nuvisertib + Momelotinib (Arm 3) – Phase 1 and 2: Response evaluation per the revised IWG-MRT criteria: - Complete remission (CR), partial remission (PR), clinical improvement (CI), stable disease (SD), and progressive disease (PD)., Nuvisertib + Momelotinib (Arm 3) – Phase 1 and 2: PK parameters of TP-3654 and momelotinib: Cmax, tmax, AUC, t½ and others as data permits.

No related papers found yet.

Austria, Belgium, Bulgaria, Czechia, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, Spain