Study Evaluating AMG 424 in Subjects With Multiple Myeloma

Part 1 of the study is dose evaluating and aimed at assessing the safety and tolerability of
AMG 424 while determining the maximum tolerated dose (MTD) and/or biologically active dose in
subjects with relapsed/ refractory multiple myeloma.

Part 2 of the study will further evaluate safety and tolerability of the AMG 424 MTD dose
determined in Part 1, in groups of subjects with relapsed/ refractory multiple myeloma that
include those with high or low cytogenetic risk.

Inclusion Criteria:

- Multiple myeloma meeting the following criteria:

- Pathologically-documented diagnosis of multiple myeloma that has relapsed after 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