Study Evaluating AMG 424 in Subjects With Multiple Myeloma

A Phase 1, First-in-Human, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 424 in Subjects With Multiple Myeloma

A multi-center Phase 1, First-in-Human study conducted in 2 Parts, testing AMG 424 in subjects with relapsed/ refractory 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 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