AMG 176 First in Human Trial in Participants With Relapsed or Refractory Multiple Myeloma and Participants With Relapsed or Refractory Acute Myeloid Leukemia

INCLUSION CRITERIA:

• For participants in Japan only: if a participant is younger than 20 years at thetime of signing the informed consent form, informed consent must be obtained fromboth the participant and his/her legal representative

• (Multiple myeloma [MM] participants) Pathologically documented, multiple myelomarelapsed or refractory disease after at least 2 lines of therapy

• (MM participants only) Measurable disease per the International Myeloma WorkingGroup response criteria

• (Acute myeloid leukemia [AML] participants) AML as defined by the World HealthOrganization Classification persisting or recurring following one or more treatmentcourses, and for participants in Japan, determined by the investigator to be noteligible for approved anticancer drug therapy in Japan; EXCEPT acute promyelocyticleukemia.

• (AML participants only) More than 5% blasts in bone marrow and Circulating whiteblood cells < 25,000/ul.

• Must be willing and able to undergo a core bone marrow biopsy (MM participants only)and bone marrow aspirate (MM and AML participants) at screening.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2,

• (MM partiicpants only) Satisfactory hematological function without transfusion orgrowth factor support

• Life expectancy of > 3 months, in the opinion of the investigator

• Adequate hepatic function

• Adequate cardiac function

• Adequate renal function

• Female participants of childbearing potential must have a negative serum or urinepregnancy test

• Other inclusion criteria may apply

EXCLUSION CRITERIA:

• Previously received an allogeneic stem cell transplant within 6 months OR havingreceived immunosuppressive therapy within the last three months OR having signs orsymptoms of acute or chronic graft-versus-host disease

• Autologous stem cell transplant less than 90 days prior to study day 1

• (MM participants only) MM with Immunoglobulin M subtype

• (MM participants only) Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonalprotein, Skin changes syndrome

• (MM participants only) Existing plasma cell leukemia

• (MM participants only) Waldenstrom's macroglobulinemia

• (MM participants only) Amyloidosis

• Infection requiring intravenous anti-infective treatments within 1 week of studyenrollment (day 1)

• Myocardial infarction within 6 months of enrollment, symptomatic congestive heartfailure (New York Heart Association > class II)

• History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 6 months prior to enrollment

• Currently receiving treatment in another investigational device or drug study. Otherinvestigational procedures while participating in this study will be allowed ifapproved by Amgen medical monitor

• Participants with elevated cardiac troponin above the manufacturer's 99th percentileupper reference limit for ADVIA Centaur XP assay at screening performed by thecentral laboratory

• Participants with evidence of recent cardiac injury at screening based on creatinekinase-muscle/brain, N-terminal prohormone of brain natriuretic peptide, andelectrocardiogram

• Other exclusion criteria may apply

• (AML Part 3d only) History of QT prolongation, torsades de pointes, ventriculartachycardia and cardiac arrest

• History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection unless agreed upon with medical monitor.