Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF)

This is a Phase 1/2 study that is currently enrolling Janus kinase 2 (JAK2) failures into the Phase 2 portion of the study.

Inclusion Criteria:

• Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy
• MF patients must have received prior JAK2 inhibitor therapy, and been found to be intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on investigator assessment
• ≥18 years old
• ECOG Performance Status of ≤ 3
• Estimated life expectancy of ≥12 weeks
• Male or non-pregnant, non-lactating female patients
• Serum creatinine of ≤1.5 × the upper limit of normal (ULN)OR estimated creatinine clearance (CrCl) ≥ 40 ml/min/1.73 m2
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × the upper limit of normal (ULN) and total bilirubin ≤1.5 × ULN. If the total bilirubin is elevated between 1.5 x and 3 x ULN, patients with a direct bilirubin ≤ 1.5 X ULN are eligible during the Phase II portion.
• Absolute neutrophil count (ANC) >1000/μL and Platelet count > 25,000/μL
• QTcB ≤ 480 msec
• No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including any use of corticosteroids for Myelofibrosis symptom or blood count management. Low dose corticosteroids ≤ 10 mg/day prednisone or equivalent is allowed for non-myelofibrosis purposes.

Exclusion Criteria:

• Active, uncontrolled systemic infection
• Patients with any unresolved toxicity greater than Grade 1 from previous anticancer therapy
• Potentially curative therapy is available
• Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4
• Patients with a serious cardiac condition within the past 6 months
• Pregnant or lactating
• Radiation therapy for splenomegaly within 6 months prior to study entry
• Splenectomy (Phase 2 portion of the study only)
• Known HIV positive status
• Known active hepatitis, a history of viral hepatitis B or hepatitis C