A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Subjects With Myelofibrosis

Inclusion Criteria:

Cohort A only

• Receiving ruxolitinib dose of less than 20 mg daily with no dose increase or no dose
modification in the last 8 weeks before screening visit.

Cohort B only

• Must have had initial reduction in spleen on ruxolitinib treatment:

- Followed by documented evidence of progression in spleen length or volume OR

- Discontinued ruxolitinib for hematologic toxicities, after the initial reduction in
spleen length or volume.

All subjects

- Confirmed diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or
post-essential thrombocythemia myelofibrosis according to revised World Health
Organization 2016 criteria.

- Must have palpable spleen of ≥ 5 cm below the left subcostal margin on physical
examination at the screening visit.

- Eastern Cooperative Oncology Group performance status of 0, 1, or 2.

- Screening bone marrow biopsy specimen available or willingness to undergo a bone
marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week
24.

- Life expectancy of at least 24 weeks.

- Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

- Lack of recovery from all toxicities from previous therapy (except ruxolitinib) to
Grade 1 or better.

- Previous treatment with itacitinib or JAK1 inhibitors (JAK1/JAK2 inhibitor ruxolitinib
is permitted).

- Inability to swallow food or any condition of the upper gastrointestinal tract that
precludes administration of oral medications.

- Recent history of inadequate bone marrow reserve as demonstrated by protocol-defined
criteria.

- Inadequate liver function at screening and baseline visits as demonstrated by
protocol-defined criteria.

- Inadequate renal function at screening and baseline visits as demonstrated by
protocol-defined criteria.

- Active bacterial, fungal, parasitic, or viral infection that requires therapy.

- Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of
reactivation: HBV DNA and HCV RNA must be undetectable. Subjects cannot be positive
for hepatitis B surface antigen or anti-hepatitis B core antibodies. Subjects who have
positive anti-HBs as the only evidence of prior exposure may participate in the study
provided that there is both 1) no known history of HBV infection and 2) verified
receipt of hepatitis B vaccine.

- Known human immunodeficiency virus infection.

- Clinically significant or uncontrolled cardiac disease.

- Active invasive malignancy over the previous 2 years except treated basal or squamous
carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix,
and completely resected papillary thyroid and follicular thyroid cancers. Subjects
with malignancies with indolent behavior such as prostate cancer treated with
radiation or surgery may be enrolled as long as they have a reasonable expectation to
have been cured with the treatment modality received.

- Splenic irradiation within 6 months before receiving the first dose of itacitinib.

- Use of any prohibited concomitant medications.

- Active alcohol or drug addiction that would interfere with their ability to comply
with the study requirements.

- Use of any potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5
half-lives (whichever is longer) before the first dose of itacitinib or anticipated
during the study.

- Use of concomitant treatment of fluconazole at a dose > 200 mg (for ruxolitinib
subjects treated in Cohort A only).

- Inadequate recovery from toxicity and/or complications from a major surgery before
starting therapy.

- Currently breastfeeding or pregnant.