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

At least one dose level of AMG 176 will achieve acceptable safety and tolerability in participants with relapsed or refractory multiple myeloma and participants with relapsed or refractory acute myeloid leukemia

This is a Phase 1, first-in-human, multicenter; non-randomized, open-label and dose-exploration study of AMG 176 administered IV in participants with relapsed or refractory multiple myeloma and participants with relapsed or refractory acute myeloid leukemia The study will be conducted in five parts.

Eligibility Criteria:
INCLUSION CRITERIA:

* For participants in Japan only: if a participant is younger than 20 years at the time of signing the informed consent form, informed consent must be obtained from both the participant and his/her legal representative
* (Multiple myeloma \[MM\] participants) Pathologically documented, multiple myeloma relapsed or refractory disease after at least 2 lines of therapy
* (MM participants only) Measurable disease per the International Myeloma Working Group response criteria
* (Acute myeloid leukemia \[AML\] participants) AML as defined by the World Health Organization Classification persisting or recurring following one or more treatment courses, and for participants in Japan, determined by the investigator to be not eligible for approved anticancer drug therapy in Japan; EXCEPT acute promyelocytic leukemia.
* (AML participants only) More than 5% blasts in bone marrow and Circulating white blood 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 or growth 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 urine pregnancy test
* Other inclusion criteria may apply

EXCLUSION CRITERIA:

* Previously received an allogeneic stem cell transplant within 6 months OR having received immunosuppressive therapy within the last three months OR having signs or symptoms 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, Monoclonal protein, 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 study enrollment (day 1)
* Myocardial infarction within 6 months of enrollment, symptomatic congestive heart failure (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. Other investigational procedures while participating in this study will be allowed if approved by Amgen medical monitor
* Participants with elevated cardiac troponin above the manufacturer's 99th percentile upper reference limit for ADVIA Centaur XP assay at screening performed by the central laboratory
* Participants with evidence of recent cardiac injury at screening based on creatine kinase-muscle/brain, N-terminal prohormone of brain natriuretic peptide, and electrocardiogram
* Other exclusion criteria may apply
* (AML Part 3d only) History of QT prolongation, torsades de pointes, ventricular tachycardia and cardiac arrest
* History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor.