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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 176 in Subjects With Relapsed or Refractory Multiple Myeloma and Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02675452
• Other study ID #: 20150161
• Secondary ID: 2015-004777-32
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 13, 2016
• Est. completion date: June 28, 2024

Study information

• Verified date: February 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 142
• Est. completion date: June 28, 2024
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Acute Myeloid Leukemia
• Relapsed or Refractory Multiple Myeloma

Intervention

Drug:
• AMG 176
Study Drug
• Azacitidine
Non-investigational product
• Itraconazole
Non-investigational product

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University Health Network-Princess Margaret Cancer Centre	Toronto	Ontario
Germany	Universitaetsklinikum der Rheinisch-Westfaelischen Technischen Hochschule Aachen	Aachen
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Universitaetsklinikum Ulm	Ulm
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi	Aichi
Japan	National Hospital Organization Okayama Medical Center	Okayama-shi	Okayama
Japan	NTT Medical Center Tokyo	Shinagawa-ku	Tokyo
United States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Chicago Hospital	Chicago	Illinois
United States	City of Hope National Medical Center	Duarte	California
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	University of California Davis Medical Center	Sacramento	California
United States	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Multiple Myeloma (MM) Part 1a Incidence of dose-limiting toxicities (DLTs)	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the maximum tolerated dose (MTD) for two-consecutive days per week dosing schedule (QD2)	Up to 6 months
Primary	MM Part 1a Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 18 months
Primary	MM Part 1a Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 18 months
Primary	MM Part 1a Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 6 months
Primary	MM Part 1a Incidence of clinically significant changes in electrocardiograms (ECGs)	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 6 months
Primary	MM Part 1a Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for QD2	Up to 6 months
Primary	MM Part 1a Pharmacokinetic (PK) parameters for AMG 176: maximum observed concentration (Cmax)	Evaluate the pharmacokinetics (PK) of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	MM Part 1a Pharmacokinetic parameters for AMG 176: area under the concentration-time curve (AUC)	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	MM Part 1a Pharmacokinetic parameters for AMG 176: clearance (CL)	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	MM Part 1a Pharmacokinetic parameters for AMG 176: half-life (t1/2)	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	MM Part 1b Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a once weekly (QW) dosing schedule	Up to 6 months
Primary	MM Part 1b Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 18 months
Primary	MM Part 1b Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 18 months
Primary	MM Part 1b Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 6 months
Primary	MM Part 1b Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 6 months
Primary	MM Part 1b Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory MM and determine the MTD for a QW dosing schedule	Up to 6 months
Primary	MM Part 1b Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	MM Part 1b Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	MM Part 1b Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	MM Part 1b Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	Acute Myeloid Leukemia (AML) Part 3a Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3a Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 18 months
Primary	AML Part 3a Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 18 months
Primary	AML Part 3a Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3a Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3a Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy in subjects with relapsed or refractory AML and determine the MTD for QD2 dosing as a monotherapy in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3a Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	AML Part 3a Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	AML Part 3a Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	AML Part 3a Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy QD2	1 month on treatment
Primary	AML Part 3b Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3b Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 18 months
Primary	AML Part 3b Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 18 months
Primary	AML Part 3b Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3b Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3b Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 monotherapy (QW) in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3b Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	AML Part 3b Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	AML Part 3b Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	AML Part 3b Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy QW	1 month on treatment
Primary	AML Part 3c Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3c Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 18 months
Primary	AML Part 3c Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 18 months
Primary	AML Part 3c Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3c Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3c Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 QW monotherapy in participants in Japan with relapsed or refractory AML	Up to 6 months
Primary	AML Part 3c Pharmacokinetic parameters for AMG 176: Cmax	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
Primary	AML Part 3c Pharmacokinetic parameters for AMG 176: AUC	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
Primary	AML Part 3c Pharmacokinetic parameters for AMG 176: CL	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
Primary	AML Part 3c Pharmacokinetic parameters for AMG 176: t1/2	Evaluate the PK of AMG 176 when administered as monotherapy (QW) in Japan	1 month on treatment
Primary	AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: Cmax	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Primary	AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: AUC	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Primary	AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: CL	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Primary	AML Part 3d Pharmacokinetic parameters for AMG 176 and itraconazole: t1/2	Evaluate the PK of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Primary	AML Part 4 Incidence of DLTs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the maximum tolerated combination dose (MTCD) of AMG 176 in combination with azacitidine	Up to 6 months
Primary	AML Part 4 Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 18 months
Primary	AML Part 4 Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 18 months
Primary	AML Part 4 Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 6 months
Primary	AML Part 4 Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 6 months
Primary	AML Part 4 Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML and determine the MTCD of AMG 176 in combination with azacitidine	Up to 6 months
Primary	AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: CL	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 4 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 5 Incidence of treatment-related adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 18 months
Primary	AML Part 5 Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 18 months
Primary	AML Part 5 Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 5 Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 5 Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 in combination with azacitidine in subjects with relapsed or refractory AML	Up to 6 months
Primary	AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: Cmax	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: AUC	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: CL	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Primary	AML Part 5 Pharmacokinetic parameters for AMG 176 and azacitidine: t1/2	Evaluate the PK of AMG 176 and azacitidine when administered in combination	1 month on treatment
Secondary	MM Part 1a Overall response (OR) according to International Myeloma Working Group uniform response criteria (IMWG-URC) for MM subjects	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1a Progression-free survival (PFS)	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1a Time to response	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1a Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 QD2 when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1a BAX and caspase 3 expression in circulating monocytes and /or circulating monocyte counts	Demonstrate inactivation of myeloid cell leukemia sequence 1 (MCL1) by the increase of active Bcl 2 associated X protein (BAX) and caspase 3 in circulating monocytes and/or the decrease of circulating monocytes in AMG 176 QD2 treated subjects	6 months on treatment
Secondary	MM Part 1b BAX and caspase 3 expression in circulating monocytes and/or circulating monocyte counts	Demonstrate inactivation of MCL1 by the increase of active BAX and caspase 3 in circulating monocytes and /or the decrease of circulating monocytes in AMG 176 QW treated subjects	6 months on treatment
Secondary	MM Part 1b Overall response (OR) according to IMWG-URC for MM subjects	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1b Progression free survival (PFS)	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1b Time to response	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	MM Part 1b Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 QW when given as monotherapy in relapsed or refractory MM	6 months on treatment
Secondary	AML Part 3a, 3b and 3c Overall response (OR) according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017)	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 3a, 3b and 3c Event free survival (EFS)	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 3a, 3b and 3c Time to response	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 3a, 3b and 3c Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 when given as monotherapy in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 3d Incidence of treatment-emergent adverse events	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Secondary	AML Part 3d Incidence of clinically significant changes in vital signs	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Secondary	AML Part 3d Incidence of clinically significant changes in ECGs	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Secondary	AML Part 3d Incidence of clinically significant changes in clinical laboratory tests	Evaluate the safety and tolerability of AMG 176 when given alone and in combination with itraconazole in subjects with AML	3 weeks on treatment
Secondary	AML Part 4 Overall response (OR) according to the 2017 ELN criteria in AML subjects	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 4 Event free survival (EFS)	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 4 Time to response	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 4 Duration of response (DOR)	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 5 OR according to the 2017 ELN criteria in AML subjects	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 5 EFS	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 5 Time to response	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment
Secondary	AML Part 5 DOR	Evaluate preliminary efficacy of AMG 176 when given in combination with azacitidine in relapsed or refractory AML	6 months on treatment

External Links

•   AmgenTrials clinical trials website