Itacitinib in Treating Participants With Refractory Metastatic/Advanced Soft Tissue Sarcomas

Participants receive itacitinib orally (PO) once daily (QD) on days 1-28. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up between 7-30 days and then
every 12 weeks for up to 2 years.

Inclusion Criteria:

- Diagnosed with soft tissue sarcoma of appropriate subtype (reviewed either at our
center or a bone and soft tissue pathologist at a major academic center): either
leiomyosarcoma (LMS), pleomorphic undifferentiated sarcoma, synovial sarcoma, or
myxoid/round cell liposarcoma

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

- Ability to provide informed consent

- At least two prior lines of therapy

- Superficial lesion accessible for multiple biopsies; lesions should be accessible with
ultrasound at time of study entry; the tumor being biopsied cannot have been targeted
for radiation or have received prior intra-lesional treatment

- Life expectancy over 6 months in the opinion of treating physician

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 or Karnofksy PS
≥ 60

- Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L

- Platelet count ≥ 100 × 10^9/L

- Hemoglobin ≥ 9 g/dL (may have been transfused)

- Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN
for all subjects

- Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
(or local institutional standard method)

- Negative serum pregnancy test at screening for women of childbearing potential

- Highly effective contraception for both male and female subjects if the risk of
conception exists; * NOTE: women of childbearing potential and men able to father a
child must agree to use 2 highly effective contraception, defined as methods with a
failure rate of less than 1% per year; highly effective contraception is required at
least 28 days prior, throughout treatment

Exclusion Criteria:

- Known untreated brain metastasis; treated brain metastasis must have been confirmed
stable by at least one scan

- Subjects may not be receiving other investigational agents

- Prior anti-cancer therapy within 2 weeks of starting treatment

- Prior treatment with a drug targeting JAK1, JAK1/2 or STAT3 inhibitor; Food and Drug
Administration (FDA) approved small molecule tyrosine kinase inhibitors (TKIs) not
specifically designed to target this pathway are okay (e.g. pazopanib, Sutent,
sorafenib are okay)

- Known, active drug or alcohol abuse

- Uncontrolled or concurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Current oral steroid usage

- Known inflammatory or autoimmune disease which requires patient to occasionally
require high dose oral steroids

- Patients with known human immunodeficiency virus (HIV) infection must have
undetectable viral load and normal CD4 count

- Inability to swallow food, or significant gastrointestinal disorder that, in the
opinion of the investigator, could interfere with absorption of the study drug

- Previous reaction to any component of INCB039110 or known hypersensitivity to the
active substance or any of the excipients