Study Evaluating AMG 424 in Subjects with Multiple Myeloma

•Multiple myeloma meeting the following criteria: •Pathologically-documented diagnosis of multiple myeloma that has relapsed after at least two prior lines of therapy that must include a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and, where approved and available, anti-CD38 therapy in any order OR that is refractory to PI, IMiD, and anti-CD38 therapy. ◾Subjects who could not tolerate a PI, IMiDs, or a CD38-directed therapeutic antibody due to unacceptable toxicities are eligible to enroll in the study. •Measurable disease as per IMWG response criteria •Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

•Known central nervous system involvement by multiple myeloma •Previously received allogeneic stem cell transplant and one or more of the following: ◦received the transplant < 6 months prior to study Day 1 ◦received immunosuppressive therapy < 3 months prior to study Day 1 ◦any active acute graft versus host disease (GvHD), grade 2- 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment ◦any systemic therapy against GvHD < 2 weeks prior to study Day 1 •Autologous stem cell transplantation less than 90 days prior to study day 1 •Multiple myeloma with IgM subtype •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) •Evidence of primary or secondary plasma cell leukemia at the time of screening •Waldenstrom's macroglobulinemia •Amyloidosis •Dexamethasone at cumulative doses of greater than 160 mg or equivalent <3 weeks prior to study Day 1 is not allowed. Use of topical or inhaled steroids is acceptable •Anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study Day 1 •Treatment with a therapeutic antibody targeting CD38 < 12 weeks prior to study Day 1 •Systemic radiation therapy or major surgery < 28 days prior to study Day 1 as well as focal radiotherapy < 14 days prior to study Day 1. •Major surgery within 28 days prior to study Day 1