A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.

Inclusion Criteria:

• Diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis
• Palpable spleen of > 10 cm below the left subcostal margin on physical examination at the screening visit OR
• Palpable splenomegaly of 5 to 10 cm below left subcostal margin on physical exam AND active symptoms of MF at the screening visit as demonstrated by presence of 1 symptom score ≥ 5 or 2 symptom scores ≥ 3 using the Screening Symptom Form
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

• Use of experimental drug therapy for myelofibrosis, or any other standard drug (eg, danazol, hydroxyurea, etc) with the exception of ruxolitinib within 6 months of starting study (combination) therapy and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better

• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications

• Unwillingness to be transfused with blood components

• Recent history of inadequate bone marrow reserve as demonstrated by the following:

  • Platelet count < 50 × 10^9/L in the 4 weeks before screening or platelet transfusion(s) within 8 weeks before screening
  • Absolute neutrophil count levels < 0.5 × 10^9/L in the 4 weeks before screening
  • Subjects with peripheral blood blast count of > 10% at the screening or baseline hematology assessments
  • Subjects who are not willing to receive red blood cell (RBC) transfusions to treat low hemoglobin levels

• Inadequate liver function at screening as demonstrated by the following:

  • Direct bilirubin ≥ 2.0 × the upper limit of laboratory normal (ULN). (NOTE: direct bilirubin will only be determined if total bilirubin is ≥ 2.0 × ULN)
  • alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN

• Inadequate renal function at screening as demonstrated by creatinine clearance < 50 mL/min or glomerular filtration rate < 50 mL/min/1.73 m^2