A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma

This is a first in human phase 1 multicenter open label study to evaluate the safety and
tolerability of AMG 224 in subjects with relapsed or refractory multiple myeloma. The study
will be conducted in 2 parts. Part 1 is the dose-exploration and part 2 is the
dose-expansion. Study medication will be administered once every 3 weeks by IV.

Inclusion Criteria:

- Pathologically documented,multiple myeloma relapsed or refractory progressive disease
after at least 3 lines of therapy for multiple myeloma.

Prior therapeutic treatment or regimens must include proteasome inhibitors (e.g.
bortezomib) and immunomodulatory drugs (e.g. lenalidomide).

- Willing and able to undergo bone marrow aspirate per protocol (with or without bone
marrow biopsy per institutional guidelines).

- Measurable disease per the IMWG response criteria

- Hematological function, as follows, without transfusion support:

- Absolute neutrophil count ≥ 1.0 X 10 9/L,

- Platelet count ≥ 75 X 109/L (in patients with < 50% of bone marrow nucleated cells
were plasma cells) or ≥ 50 X 109/L (in patients with ≥ 50% of bone marrow nucleated
cells were plasma cells) without transfusion or growth factor support

- Hemoglobin > 8 g/dL (> 80 g/L)

- Adequate renal and hepatic function

- Left ventricular ejection fraction (LVEF) > 50%

Exclusion Criteria:

- Currently receiving treatment in another investigational device or drug study, or less
than 28 days since ending treatment on another investigational device or drug study

- Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, or
investigational agent) within 28 days prior to study day 1

- Multiple myeloma with IgM subtype

- Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to
study day

- Autologous stem cell transplant less than 90 days prior to study day 1

- POEMS syndrome, Plasma cell leukemia, Waldenstrom's macroglobulinemia or Amyloidosis

- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart
failure (New York Heart Association > class II)

- A baseline ECG QTcF > 470 msec