Study of INCB040093 in Subjects With Previously Treated B-Cell Malignancies

A Phase 1, Open-label, Dose Escalation, Safety and Tolerability Study of INCB040093 in Subjects With Previously Treated B-Cell Malignancies

The study will be conducted in three parts. Part 1 is a dose escalation phase to determine the maximum tolerated dose (MTD) of INCB040093, a PI3Kδ inhibitor, or a tolerated, pharmacologically active dose; Part 2 will evaluate the combination of INCB040093 and itacitinib (INCB039110), a JAK1 inhibitor, to determine the MTD of the combination or a tolerated dose that produces substantial pharmacologic inhibition of both targets; Part 3 will further evaluate the chosen doses of INCB040093 alone and in combination with itacitinib (INCB039110) in subjects with relapsed/refractory B-cell malignancies.

Inclusion Criteria:

• Aged 18 years or older, with lymphoid malignancies of B-cell origin as follows:

*Indolent / aggressive B-cell (NHL) Non- Hodgkin's Lymphoma:

EXCLUDING: Burkitt 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, Waldenstrom macroglobulinemia, Mantle cell lymphoma, transformed NHL histologies, etc.

*Hodgkin's lymphoma

• Life expectancy of 12 weeks or longer.
• Subject must have received ≥ 1 prior treatment regimen.
• The subject must not be a candidate for potentially curative therapy, including stem cell transplant.

Exclusion Criteria:

• Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug.
• Received any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) prior to receiving their first dose of study drug (42 days for nitrosoureas) EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent).
• Has any unresolved toxicity ≥ Grade 2 from previous anticancer therapy.
• Has history of brain metastases or spinal cord compression, or lymphoma involving the central nervous system.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3.
• Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or is currently receiving immunosuppressive therapy following allogeneic transplant.
• Received autologous hematopoietic stem cell transplant within the last 3 months.
• Laboratory parameters not within the protocol-defined range.
• Current or recent history (<30 days prior to screening and/or <45 days prior to dosing) of a clinically meaningful bacterial, fungal, parasitic or mycobacterial infection.
• Current clinically active viral infection.
• Known history of infection with the human immunodeficiency virus (HIV).
• History of active hepatitis or positive serology for hepatitis.