A Phase 1, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 Monotherapy and in Combination With INCB039110 in Subjects With Previously Treated B-Cell Malignancies

UMCC 2014.144

Open-label, dose-escalation study in subjects with previously treated B-cell malignancies to find maximum tolerated dose (MTD) or pharmacologic active dose of a PI3Kδ inhibitor, INCB050465, as monotherapy and in combination with INCB039110, a JAK1 inhibitor. INCB050465 inhibits PI3Kδ, a protein involved in growth and survival of B-cell cancer cells.

Moshe Talpaz, M.D.

Tycel Phillips, M.D.

Inclusion Criteria:

• Aged 18 years or older, with lymphoid malignancies of B-cell origin including:
  a. Indolent / aggressive B-cell non-Hodgkin's lymphoma (NHL)
  EXCLUDING: Burkitt's lymphoma and precursor B lymphoblastic leukemia/lymphoma
  INCLUDING: any non-Hodgkin's B cell malignancy such as CLL and rare non-Hodgkin's B- cell subtypes such as hairy cell leukemia, Waldenström macroglobulinemia (WM), MCL, and transformed NHL histologies
  b. Hodgkin's lymphoma (HL)
• Life expectancy of 12 weeks or longer.
• Subject must have received ≥ 1 prior treatment regimen(s).
• The subject must not be a candidate for potentially curative therapy including hematopoietic stem cell transplantation.

Exclusion Criteria:

• Has history of brain metastasis, spinal cord compression, or lymphoma involving the central nervous system (CNS).
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3 (≥ 2 during dose escalation).
• Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or currently receiving immunosuppressive therapy following allogeneic transplant.
• Received autologous hematopoietic stem cell transplant within the last 3 months.
• Inadequate marrow reserve assessed by hematologic laboratory parameters
• Inadequate renal or liver function
• Known HIV infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation.