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

Study Overview
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Brief Summary
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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.

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

Conditions
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B-cell Malignancies

Intervention / Treatment
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* Drug: INCB040093
* Drug: INCB040093
* Drug: INCB040093 + itacitinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB040093<br> | Drug: INCB040093<br>* Escalating doses starting at 100 mg every day (QD)<br>Drug: INCB040093<br>* INCB040093 monotherapy - dose to be determined at completion of Phase I of the study<br>|
| Experimental: INCB040093 in combination with itacitinib (INCB039110)<br> | Drug: INCB040093 + itacitinib<br>* INCB040093 dose to be determined at completion of Part 1 of the study + itacitinib at a starting dose of 400 mg, QD with escalations planned up to 600 mg QD.<br>* Other names: itacitinib (INCB039110);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of INCB040093 as monotherapy and when given in combination with itacitinib as determined by clinical laboratory assessments, physical exams, 12-lead ECG and summary of adverse events |  | Measured every 3 weeks until progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy as assessed by Overall Response Rate (ORR) as measured by published criteria for Hodgkin's/non-Hodgkin's lymphoma (Cheson et al 2007 and Owen et al 2013) and Chronic Lymphocytic Leukemia (CLL) (Cheson et el 2012) |  | Every 12 weeks (4 cycles) until study withdrawal | 
| Pharmacokinetic (PK) collections. | Plasma concentrations of each INCB040093 and itacitinib will be used to estimate peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC). | Measured for each patient at Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 15 |