A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)

The study will sequentially evaluate AGS67E given as a 30 minute intravenous (IV) infusion in
two different schedules: once every 3 weeks (Q3) and then once weekly for 3 weeks.

The dose escalation follows a 3 + 3 design.

The Data Review Team may expand any dose level or intermediate dose level that has been
deemed safe and resulted in at least one subject with a Composite Complete Remission (CRc).
An expansion cohort may enroll up to 15 subjects.

Inclusion Criteria:

- Subject has morphologically documented primary or secondary AML by the World Health
Organization (WHO) criteria (2008) and fulfills one of the following:

- Refractory to at least 1 cycle of induction chemotherapy

- Relapsed after achieving remission with a prior therapy

- Patients with untreated AML who are either unwilling or unable to undergo
high-dose induction/consolidation intensive chemotherapy

- Circulating blasts < 20,000 (cytoreduction with hydroxyurea is allowed)

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

- Subject has adequate renal function: serum creatinine ≤ 2.0 mg/dL and estimated
creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation

- Subject has a total bilirubin ≤ 1.5 x upper limit of normal (ULN), albumin ≥ 2.5 g/dL,
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

- Negative pregnancy test in women of child bearing potential

- Sexually active fertile subjects, and their partners, must agree to use medically
accepted double-barrier methods of contraception (e.g., barrier methods, including
male condom, female condom, or diaphragm with spermicidal gel) during the study and at
least 6 weeks after termination of study therapy

Exclusion Criteria:

- Subject has a diagnosis of acute promyelocytic leukemia

- Subject has preexisting sensory or motor neuropathy Grade ≥ 2 at baseline

- Subject has received small molecule therapy, radiotherapy, immunotherapy, monoclonal
antibodies, investigational drug, or chemotherapy within 14 days before first dose of
study drug, with the exception of hydroxyurea

- P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days before the first
dose of drug, with the exception of the antibiotics/ antifungals used as prophylaxis
and/or supportive care

- Any Grade ≥ 2 persistent non-hematological toxicity related to allotransplant

- Graft-Versus-Host Disease (GVHD) therapy within 6 weeks before the first dose of study
drug; low dose steroids (≤ 10mg) allowed

- Subject has known current central nervous system (CNS) disease

- Active angina or Class III or IV Congestive Heart Failure (New York Heart Association
CHF Functional Classification System) or clinically significant cardiac disease within
6 months of the first dose of study drug, including myocardial infarction, unstable
angina, Grade 2 or greater peripheral vascular disease, congestive heart failure,
uncontrolled hypertension, or arrhythmias not controlled by medication

- Subject has clinical evidence of Disseminated Intravascular Coagulation (DIC)

- Subject has known positivity for human immunodeficiency virus (HIV)

- Subject has know positivity for Hepatitis B surface antigen test or Hepatitis C
Antibody

- Subject has an uncontrolled active infection requiring treatment and fever 38.3°C or
higher 48 hours before the first dose of study drug. Controlled infections (i.e. 3
negative cultures completing antibiotics and/or stable fungal infection in therapy are
allowed provided the subject has a temperature of <38.3°C within 48 hours of the first
dose of study drug

- Subject has known sensitivity to any of the components of the investigational product
AGS67E:

- AGS67E

- L-Histidine

- α-trehalose dihydrate or

- polysorbate 20

- Major surgery within 28 days of the first dose of study drug

- Subject is pregnant or lactating

- Subject has a condition or situation which may put the subject at significant risk,
may confound the study results, or may interfere significantly with subject's
participation in the study