Study of INCB053914 in Subjects With Advanced Malignancies

Inclusion Criteria:

- Aged 18 years or older

- Confirmed diagnosis of select advanced malignancy

- Parts 1 and 2:

- Unresponsive to currently available therapy and there is no standard-of-care
therapy available in the judgment of the investigator.

- Not currently a candidate for curative treatment

- Parts 3 and 4:

- Subjects with relapsed/refractory AML must have received either induction
chemotherapy for AML or hypomethylating agents for hematologic disease before
AML.

- Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive
and unfit for intensive chemotherapy.

- Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months
with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to
25 mg BID).

- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival
sample obtained since completion of most recent therapy (as appropriate to subjects
with existing bone marrow disease or for whom bone marrow examination is a component
of disease status assessment)

- Eastern Cooperative Oncology Group (ECOG) performance status

- Part 1: 0 or 1

- Parts 2, 3 and 4: 0, 1, or 2

- Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.

Exclusion Criteria:

- Inadequate bone marrow or organ function

- Received an investigational agent within 5 half-lives or 14 days, whichever is longer,
prior to receiving the first dose of study drug

- Received non-biologic anticancer medication within 5 half-lives prior to receiving the
first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28
days for any antibodies or biological therapies

- Prior receipt of a PIM inhibitor

- Any history of disease involving the central nervous system (Part 1). Known active
disease involving the central nervous system (Part 2).

- Screening corrected QT interval (QTc) interval > 470 milliseconds

- Radiotherapy within the 2 weeks prior to initiation of treatment

- Chronic or current active infection requiring systemic antibiotic, antifungal, or
antiviral treatment