Study Evaluating AMG 424 in Subjects With Multiple Myeloma

Inclusion Criteria

• 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

Exclusion Criteria

• 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