A Phase 1b Rising Multiple-Dose Study to Evaluate Safety, Tolerability and Activity of KX2-391 in Elderly Subjects With Acute Myeloid Leukemia Who Are Refractory to or Have Declined Standard Induction Therapy

Inclusion Criteria:

- Written informed consent.

- Either de novo or secondary AML by 2008 World Health Organization (WHO)
classification.

- A bone marrow biopsy and aspirate sample must be obtained between Day -14 to Day -1,
and this sample must be confirmed to be adequate for morphologic analysis of marrow
cellularity and blast percentage before the first dose of KX2-391 is administered.

- A bone aspirate sample (with or without biopsy) must be obtained after the patient
signs the informed consent document and be submitted for baseline pharmacodynamic
assessment. Although this will usually be obtained as part of the baseline assessment
marrow biopsy and aspirate procedure described above, if a complete marrow evaluation
was performed prior to the patient signing informed consent, a dedicated bone marrow
aspiration for this sample can be performed after the patient signs informed consent,
so long as the pre-consent biopsy and aspirate procedure were done within 14 days of
the first dose of KX2-391.

- Adults age ≥ 60 years of age

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Life expectancy of at least 6 weeks from first day of study drug administration

- Adequate liver function (AST/ALT < 3 x upper limit of normal (ULN), Alk Phos < 2.5 x
ULN, and Direct Bilirubin < 1.5 x ULN)

- Adequate renal function (serum creatinine < 1.5 x ULN)

- Documented QTc ≤ 0.48 seconds within 14 days of first dose of KX2-391

Exclusion Criteria:

- Subjects with acute promyelocytic leukemia (APL, AML FAB type M3), or chronic
myelogenous leukemia (CML).

- Have not resolved toxicity from previous anticancer treatments or investigational
agents, other than hematologic toxicities or alopecia, to ≤ Grade 1 according to the
most recent CTCAE guidelines.

- Subjects with rapidly proliferative AML that is likely to require treatment within
the next 30 days (e.g. hydroxyurea).

- Received an investigational agent within 5 half-lives of that agent from the
anticipated Cycle 1 Day 1 of treatment with KX2-391.

- Have clinical evidence of central nervous system involvement by AML or other
malignancy.

- History of major surgery to the upper gastrointestinal tract, or have a history of
inflammatory bowel disease, malabsorption syndrome, or other medical condition that
may interfere with oral drug absorption.

- Uncontrolled hypertension (at time of dosing).

- Other medical conditions which, in the opinion of the investigator, make it
undesirable for the subject to participate in the study.

- Known history of hepatitis B, C, or human immunodeficiency (HIV) infection.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection. Patients receiving intravenous antibiotics for infections that are under
control may be included in this study.

- Subjects who are unwilling or unable to comply with the protocol.

- Subjects who are taking moderate or strong CYP450 3A4 modulators, with the exception
of fluconazole (see Appendix 2 for list of medications currently known to be moderate
or strong CYP450 3A4 modulators). Subjects who can safely discontinue these
medications can become eligible for this trial.

- Subjects receiving azole-based antifungal prophylaxis other than fluconazole (see
Appendix 2) who are unable to switch their prophylaxis to fluconazole, or discontinue
antifungal prophylaxis, for 7 days prior to first day of study drug administration.

- Active cancer, other than AML, requiring systemic chemotherapy or biological therapy
within 6 months of study entry. Patients who have received only hormonal therapy in
the neoadjuvant or adjuvant setting in the past 6 months may participate in this
study.

- Symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia.

- Other conditions that could jeopardize the subject's ability to comply with the
protocol, including, but not limited to, dementia, psychosis, or other major
psychiatric disorder

- Pregnant or breast feeding