Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma

Inclusion Criteria:

- Cytologically or histologically confirmed diagnosis of multiple myeloma

- Subjects must have received at least 1 and not more than 3 previous lines of
treatment and have had a response to treatment (i.e., achieved a minimal response
[MR] or better) according to the International Myeloma Working Group (IMWG) uniform
response criteria

- Subjects must have had progressive disease according to the IMWG uniform response
criteria following the last multiple myeloma treatment

- Subjects must have measurable disease defined as at least 1 of the following
(according to central laboratory results):

- Serum M-protein ≥1 g/dL

- Urine M-protein ≥200 mg/24 hours

- Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio

- ≥1 bone lesion identifiable by radiograph, computed tomography, magnetic resonance
imaging, or bone scintigraphy

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2

- Subjects must be nonrefractory to bortezomib and had no progression during or within
60 days after completion of bortezomib

- Absolute neutrophil count (ANC) ≥1.5 × 10e9/L, hemoglobin (Hb) ≥9.0 g/dL, and
platelet count ≥75.0 × 10e9/L independent of transfusion of red blood cells (RBC) or
platelet concentrates and independent of granulocyte colony stimulating factor
(G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF)

Exclusion Criteria:

- Systemic glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within
the last 4 weeks prior to first dose, unless tapered and on a stable dose ≤10 mg/day
for at least 1 week

- Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy,
monoclonal protein, and skin changes) or light chain (AL) amyloidosis

- Plasma cell leukemia

- Systemic anti-cancer therapy within 4 weeks prior to first dose

- Radiation therapy in the previous 4 weeks prior to first dose except if given for
pain management and involves less than 10% of the bone marrow

- Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical

- Congestive heart failure (New York Heart Association [NYHA] class III to IV),
symptomatic cardiac ischemia, cardiomyopathy, clinically relevant ventricular
arrhythmia, pericardial disease, unstable angina or myocardial infarct in the
previous 6 months prior to first dose, left ventricular ejection fraction <40%

- Neuropathy ≥ Grade 2 or Grade 1 with pain