Relapsed or Refractory Acute Myeloid Leukemia, Relapsed or Refractory Multiple Myeloma
Conditions
Brief summary
The main objectives are to evaluate the safety and tolerability of AMG 176 monotherapy in participants with relapsed or refractory multiple myeloma and participants with relapsed or refractory acute myeloid leukemia.
Detailed 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.
Interventions
DRUGAMG 176
Study Drug
DRUGAzacitidine
Non-investigational product
DRUGItraconazole
Non-investigational product
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life (t1/2) of AMG 176 | Parts 1B, 3B, 3C, 3A (cohort 4) Cycle 1: day 1 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 8 pre, EOI; Part 3D also days 9, 15 pre and EOI; Parts 1A, 3 (except cohort 4), 4: also day 2 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 9 pre and EOI | Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis. |
| AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Parts 1B, 3B, 3C, and 3 (cohort 4): Cycle 1 day 1 pre, EOI, 1, 2, 3, 5, and 7 hrs EOI, cycle 1 day 8 pre, EOI; Part 3d also cycle 1 day 15 pre and EOI | Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis. |
| Clearance (CL) of AMG 176 | Parts 1B, 3B, 3C, 3A (cohort 4) Cycle 1: day 1 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 8 pre, EOI; Part 3D also days 9, 15 pre and EOI; Parts 1A, 3 (except cohort 4), 4: also day 2 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 9 pre and EOI | Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis. Clearance was calculated as Dose/ AUC0-144 for Parts 1A, 3A, and 4; and as Dose/AUC0-168 for Parts 1B, 3 (Cohort 4 only) 3B, 3C, and 3D. |
| Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Parts 1A, 3A and, 4: Cycle 1 day 1 pre, EOI, 1, 2, 3, 5, and 7 hrs EOI, cycle 1 day 8 pre and EOI | Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis. |
| AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Parts 1A, 3A, and 4: Cycle 1 day 2 pre, EOI, 1, 2, 3, 5, and 7 hrs EOI, cycle 1 day 9 pre and EOI | Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis. |
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | Days 1 to 28 of cycle 1 (4 weeks) | A DLT was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0, and considered by the investigators to be related to AMG 176. A DLT was defined as a grade 3 or higher non-hematological or a grade 4 hematologic adverse event (AE) that occurred during the DLT observation period. CTCAE is graded from grade 1 to 5, with higher grades indicating a worse outcome, and included; grade 1 = mild, grade 2= moderate, grade 3 = severe, grade 4 = life-threatening, and grade 5 = death. |
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Day 1 cycle 1 to 30 days after the last dose of AMG 176; median treatment duration was 1.2 months | An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (AMG 176) up to 30 days after the end of investigational product. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests were reported as TEAEs. A treatment-related AE was any TEAE that per investigator review had a reasonable possibility of being caused by the investigational product (AMG 176). |
| Maximum Observed Concentration (Cmax) of AMG 176 | Parts 1B, 3B, 3C, 3A (cohort 4) Cycle 1: day 1 pre, end of infusion (EOI), 1, 2, 3, 5, 7 hrs EOI, day 8 pre, EOI; Part 3D also days 9, 15 pre and EOI; Parts 1A, 3 (except cohort 4), 4: also day 2 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 9 pre and EOI | Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantification (LLOQ) of 5.00 ng/mL were set to zero before data analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | Day 1 cycle 1 to end of study; median duration from start of study treatment to end of study for all participants was 2.2 months | A response was of any of the following, per the ELN criteria: Complete remission (CR) without minimal residual disease (CRMRD-), CR, CR with incomplete hematology recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR), SD, PD. CRMRD-: CR with negativity for genetic marker by quantitative reverse transcription (RT-qPCR) or multicolor flow cytometry (MFC); CR: BM blasts \<5% bone marrow, no circulating blasts/ extramedullary disease, ANC \> 1.0 x 10\^9/L, platelets ≥ 100 x 10\^9/L; CRi: CR except for neutropenia (\< 1.0 x 10\^9/L) or thrombocytopenia (\< 100 x 10\^9/L); MLFS: BM blasts \< 5% no blasts with auer rods/extramedullary disease, no hematologic recovery; PR: hematological criteria of CR; decrease BM blast to 5-25%; decrease of BM blast percentage by ≤ 50%; SD: absence of CRMRD-, CR, CRi, PR, MLFS and criteria for PD not met; PD: evidence of increase in BM blast percentage and/or increase of absolute blast count. |
| Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | Day 1 cycle 1 to end of study; median duration from start of study treatment to end of study for all participants was 2.2 months | A response consisted of any of the following, assessed according to the IMWG-URC: stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minor response (MR), stable disease (SD), or progressive disease (PD) per IMWG-URC. CR: negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). sCR: CR and normal serum free light chain ratio and no clonal cells in BM by immunohistochemistry. VGPR: Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-hrs). PR: ≥ 50% reduction of serum M-protein and reduction in 24-hrs urinary M-protein by ≥ 90% or to \< 200 mg/24-hours; MR: 25-49% reduction in serum M-protein and 50-89% reduction in 24-hr urinary M-protein (\>200 mg/24-hrs); SD: not meeting criteria for CR, VGPR, PR, or PD; PD: ≥ 25% increase in serum or urine M-component, BM plasma cell percentages. |
Countries
Australia, Canada, Germany, Japan, United States
Participant flow
Recruitment details
Participants were enrolled at 21 study centers in the United States, Canada, Australia, Germany, and Japan, and participated from June 2016 to May 2024. The study was conducted in multiple parts and Part 5 did not enroll any participants due to early termination of the study. Part 2 was removed during a protocol amendment.
Pre-assignment details
Participants with multiple myeloma (MM) or with acute myeloid leukemia (AML) were enrolled into 29 cohorts. Dosing of AMG 176 was from Dose A (lowest) to Dose I (highest).
Participants by arm
| Arm | Count |
|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW Participants with MM received AMG 176 Dose A BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW Participants with MM received AMG 176 Dose B IV BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW Participants with MM received AMG 176 Dose C BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 4 |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW Participants with MM received AMG 176 Dose D BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW Participants with MM received AMG 176 Dose E BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW Participants with MM received AMG 176 Dose G BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 2 |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose F BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 4 |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose G BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 4 |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose H BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 5 |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose I BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 5 |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose F QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose G QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose H QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW Participants with MM received AMG 176 Dose E in cycle 1 week 1, then received Dose I QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 3A Cohort 1 (AML): AMG 176 Dose D BIW Participants with AML received AMG 176 Dose D BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 5 |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW Participants with AML received AMG 176 Dose E BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 5 |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW Participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose F BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 5 |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW Japanese participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose F QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 2 |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW Participants with AML received AMG 176 Dose E QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 4 |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW Participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose F QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 3 |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW Participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose G QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 4 |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW Japanese participants with AML received AMG 176 Dose E QW. AMG 176 was administered as an IV infusion in a 4-week cycle. | 4 |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole Participants with AML received AMG 176 Dose D QW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 200 mg itraconazole QD for 7 days in week 1. | 10 |
| Part 4 Cohort 1 (AML): AMG 176 Dose D QW + Azacitidine Participants with AML received AMG 176 Dose D QW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 75 mg/m\^2 azacitidine SC or IV QD for 7 days in week 1. | 5 |
| Part 4 Cohort 2 (AML): AMG 176 Dose E QW + Azacitidine Participants with AML received AMG 176 Dose E QW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 75 mg/m\^2 azacitidine SC or IV QD for 7 days in week 1. | 4 |
| Part 4 Cohort 3 (AML): AMG 176 Dose E Then Dose F QW + Azacitidine Participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose F QW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 75 mg/m\^2 azacitidine SC or IV QD for 7 days in week 1. | 4 |
| Part 4 Cohort 4 (AML): AMG 176 Dose E Then Dose G QW + Azacitidine Participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose G QW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 75 mg/m\^2 azacitidine SC or IV QD for 7 days in week 1. | 13 |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine Participants with AML received AMG 176 Dose E BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 75 mg/m\^2 azacitidine SC or IV QD for 7 days in week 1. | 10 |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine Participants with AML received AMG 176 Dose E in cycle 1 week 1, then received Dose G BIW. AMG 176 was administered as an IV infusion in a 4-week cycle. They also received 75 mg/m\^2 azacitidine SC or IV QD for 7 days in week 1. | 13 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 | FG026 | FG027 | FG028 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 4 | 3 | 3 | 3 | 7 | 5 | 3 | 4 | 7 | 6 | 9 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 3 | 4 |
Baseline characteristics
| Characteristic | Part 4 Cohort 4 (AML): AMG 176 Dose E Then Dose G QW + Azacitidine | Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Part 4 Cohort 2 (AML): AMG 176 Dose E QW + Azacitidine | Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Part 4 Cohort 3 (AML): AMG 176 Dose E Then Dose F QW + Azacitidine | Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Part 3A Cohort 1 (AML): AMG 176 Dose D BIW | Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Total | Part 4 Cohort 1 (AML): AMG 176 Dose D QW + Azacitidine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 - 64 years | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 51 Participants | 4 Participants |
| Age, Customized 65 - 74 years | 6 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 5 Participants | 53 Participants | 0 Participants |
| Age, Customized 75 - 84 years | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 33 Participants | 1 Participants |
| Age, Customized >=85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 10 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 5 Participants | 2 Participants | 3 Participants | 13 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 3 Participants | 10 Participants | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 7 Participants | 128 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 19 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 0 Participants | 2 Participants | 9 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 8 Participants | 107 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 6 Participants | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 50 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 5 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 7 Participants | 1 Participants | 4 Participants | 1 Participants | 4 Participants | 1 Participants | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 7 Participants | 89 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 1 / 4 | 0 / 3 | 0 / 3 | 1 / 2 | 0 / 4 | 0 / 4 | 1 / 5 | 0 / 5 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 3 | 0 / 5 | 2 / 5 | 0 / 5 | 0 / 2 | 4 / 4 | 3 / 3 | 3 / 4 | 3 / 4 | 7 / 10 | 5 / 5 | 3 / 4 | 4 / 4 | 7 / 13 | 6 / 10 | 9 / 13 |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 4 / 4 | 3 / 3 | 3 / 3 | 1 / 2 | 4 / 4 | 4 / 4 | 5 / 5 | 5 / 5 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 5 | 3 / 5 | 5 / 5 | 2 / 2 | 4 / 4 | 3 / 3 | 4 / 4 | 4 / 4 | 10 / 10 | 5 / 5 | 4 / 4 | 4 / 4 | 13 / 13 | 10 / 10 | 13 / 13 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 1 / 4 | 0 / 3 | 1 / 3 | 2 / 2 | 3 / 4 | 0 / 4 | 2 / 5 | 3 / 5 | 0 / 3 | 2 / 3 | 1 / 3 | 1 / 3 | 3 / 5 | 4 / 5 | 3 / 5 | 2 / 2 | 2 / 4 | 2 / 3 | 4 / 4 | 1 / 4 | 8 / 10 | 4 / 5 | 4 / 4 | 4 / 4 | 10 / 13 | 8 / 10 | 10 / 13 |
Outcome results
Primary
Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B])
Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis.
Time frame: Parts 1A, 3A and, 4: Cycle 1 day 1 pre, EOI, 1, 2, 3, 5, and 7 hrs EOI, cycle 1 day 8 pre and EOI
Population: The PK analysis set included all participants who had received at least 1 dose of AMG 176 and had at least 1 PK sample collected. AUC0-24 was pre-specified in Parts 1A, 3A (Cohorts 1, 2, and 3) and 4 (Cohorts 5A and 5B) and participants with data available at each time point are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 6230 hour*ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 13700 hour*ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 13900 hour*ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 21100 hour*ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 32700 hour*ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 3240 hour*ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 130000 hour*ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 48500 hour*ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 26700 hour*ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 52300 hour*ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 128000 hour*ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 128000 hour*ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 47700 hour*ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 118000 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 38500 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 176000 hour*ng/mL |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 52600 hour*ng/mL |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 18300 hour*ng/mL |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 51800 hour*ng/mL |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 44700 hour*ng/mL |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 64900 hour*ng/mL |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 30100 hour*ng/mL |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 23600 hour*ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 8 | 86800 hour*ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Area Under the Concentration-time Curve (AUC) From Time 0 to 24 Hours (AUC0-24) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 1 | 32000 hour*ng/mL |
Primary
AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B])
Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis.
Time frame: Parts 1A, 3A, and 4: Cycle 1 day 2 pre, EOI, 1, 2, 3, 5, and 7 hrs EOI, cycle 1 day 9 pre and EOI
Population: The PK analysis set included all participants who had received at least 1 dose of AMG 176 and had at least 1 PK sample collected. AUC0-144 was pre-specified in Parts 1A, 3A (Cohorts 1, 2, and 3) and 4 (Cohorts 5A and 5B) and participants with data available at each time point are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 10800 hour*ng/mL |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 540000 hour*ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 25300 hour*ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 124000 hour*ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 25700 hour*ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 234000 hour*ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 58900 hour*ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 202000 hour*ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 435000 hour*ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 87600 hour*ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 134000 hour*ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 990000 hour*ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 277000 hour*ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 518000 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 385000 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 473000 hour*ng/mL |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 34600 hour*ng/mL |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 432000 hour*ng/mL |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 81000 hour*ng/mL |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 197000 hour*ng/mL |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 122000 hour*ng/mL |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 121000 hour*ng/mL |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 63000 hour*ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 2 | 99300 hour*ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | AUC From Time 0 to 144 Hours (AUC0-144) of AMG 176 (Parts 1A, 3A [Cohorts 1, 2, and 3], and 4 [Cohorts 5A and 5B]) | Cycle 1 day 9 | 217000 hour*ng/mL |
Primary
AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D)
Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis.
Time frame: Parts 1B, 3B, 3C, and 3 (cohort 4): Cycle 1 day 1 pre, EOI, 1, 2, 3, 5, and 7 hrs EOI, cycle 1 day 8 pre, EOI; Part 3d also cycle 1 day 15 pre and EOI
Population: The PK analysis set included all participants who had received at least 1 dose of AMG 176 and had at least 1 PK sample collected. AUC0-168 was pre-specified in Parts 1B, 3 (Cohort 4), 3B, 3C, and 3D and participants with data available at each time point are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 133000 hour*ng/mL |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 185000 hour*ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 152000 hour*ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 348000 hour*ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 108000 hour*ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 345000 hour*ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 104000 hour*ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 405000 hour*ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 296000 hour*ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 199000 hour*ng/mL |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 34800 hour*ng/mL |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 82200 hour*ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 450000 hour*ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 74400 hour*ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 83700 hour*ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 272000 hour*ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 203000 hour*ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 153000 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 1 | 12800 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 8 | 25700 hour*ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | AUC From Time 0 to 168 Hours (AUC0-168) of AMG 176 (Parts 1B, 3 [Cohort 4], 3B, 3C, and 3D) | Cycle 1 day 15 | 14600 hour*ng/mL |
Primary
Clearance (CL) of AMG 176
Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis. Clearance was calculated as Dose/ AUC0-144 for Parts 1A, 3A, and 4; and as Dose/AUC0-168 for Parts 1B, 3 (Cohort 4 only) 3B, 3C, and 3D.
Time frame: Parts 1B, 3B, 3C, 3A (cohort 4) Cycle 1: day 1 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 8 pre, EOI; Part 3D also days 9, 15 pre and EOI; Parts 1A, 3 (except cohort 4), 4: also day 2 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 9 pre and EOI
Population: The PK analysis set included all participants who had received at least 1 dose of AMG 176 and had at least 1 PK sample collected. Participants with data available at each time point are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 2.77 mL/hr/m^2 |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.0556 mL/hr/m^2 |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.307 mL/hr/m^2 |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.58 mL/hr/m^2 |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.218 mL/hr/m^2 |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.95 mL/hr/m^2 |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.07 mL/hr/m^2 |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.291 mL/hr/m^2 |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.278 mL/hr/m^2 |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.36 mL/hr/m^2 |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 4.82 mL/hr/m^2 |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.242 mL/hr/m^2 |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 0.430 mL/hr/m^2 |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.756 mL/hr/m^2 |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 1.14 mL/hr/m^2 |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 0.309 mL/hr/m^2 |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 0.992 mL/hr/m^2 |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 0.886 mL/hr/m^2 |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 0.819 mL/hr/m^2 |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 0.686 mL/hr/m^2 |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 1.17 mL/hr/m^2 |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 1.10 mL/hr/m^2 |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 1.16 mL/hr/m^2 |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 1.16 mL/hr/m^2 |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.73 mL/hr/m^2 |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.544 mL/hr/m^2 |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.744 mL/hr/m^2 |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.50 mL/hr/m^2 |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 0.981 mL/hr/m^2 |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 0.652 mL/hr/m^2 |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 0.603 mL/hr/m^2 |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 3.58 mL/hr/m^2 |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 1.47 mL/hr/m^2 |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 1.88 mL/hr/m^2 |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 0.407 mL/hr/m^2 |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 1.42 mL/hr/m^2 |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 0.854 mL/hr/m^2 |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 0.782 mL/hr/m^2 |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 0.605 mL/hr/m^2 |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Clearance (CL) of AMG 176 | Cycle 1 day 1 | 4.68 mL/hr/m^2 |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Clearance (CL) of AMG 176 | Cycle 1 day 15 | 4.08 mL/hr/m^2 |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Clearance (CL) of AMG 176 | Cycle 1 day 8 | 2.26 mL/hr/m^2 |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 0.992 mL/hr/m^2 |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 0.978 mL/hr/m^2 |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Clearance (CL) of AMG 176 | Cycle 1 day 9 | 1.11 mL/hr/m^2 |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Clearance (CL) of AMG 176 | Cycle 1 day 2 | 1.20 mL/hr/m^2 |
Primary
Maximum Observed Concentration (Cmax) of AMG 176
Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantification (LLOQ) of 5.00 ng/mL were set to zero before data analysis.
Time frame: Parts 1B, 3B, 3C, 3A (cohort 4) Cycle 1: day 1 pre, end of infusion (EOI), 1, 2, 3, 5, 7 hrs EOI, day 8 pre, EOI; Part 3D also days 9, 15 pre and EOI; Parts 1A, 3 (except cohort 4), 4: also day 2 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 9 pre and EOI
Population: The PK analysis set included all participants who had received at least 1 dose of AMG 176 and had at least 1 PK sample collected. Participants with data available at each time point are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 1740 ng/mL |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 2270 ng/mL |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 2810 ng/mL |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 1780 ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 3830 ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 3830 ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 2900 ng/mL |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 3800 ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 3590 ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 3250 ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 3570 ng/mL |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 4480 ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 5650 ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 6400 ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 8270 ng/mL |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5790 ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 10100 ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 11400 ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 11800 ng/mL |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 10200 ng/mL |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 27300 ng/mL |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 27300 ng/mL |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 26100 ng/mL |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 39400 ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 15900 ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 17700 ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 10100 ng/mL |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 6500 ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 18400 ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 24700 ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 91100 ng/mL |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 7980 ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 18700 ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 5230 ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 19800 ng/mL |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 4880 ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5440 ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 31900 ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 7670 ng/mL |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 21100 ng/mL |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 7940 ng/mL |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 16100 ng/mL |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 15000 ng/mL |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 6450 ng/mL |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 12100 ng/mL |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 23800 ng/mL |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 4590 ng/mL |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 37600 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 6280 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 5580 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5140 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 9530 ng/mL |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5570 ng/mL |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 8500 ng/mL |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 8670 ng/mL |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 7250 ng/mL |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 12700 ng/mL |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 12100 ng/mL |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 6910 ng/mL |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 6250 ng/mL |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 12200 ng/mL |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 7790 ng/mL |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 3600 ng/mL |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 3770 ng/mL |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5230 ng/mL |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 6300 ng/mL |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 11100 ng/mL |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 3270 ng/mL |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 6020 ng/mL |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 6290 ng/mL |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 1850 ng/mL |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 1670 ng/mL |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 15 | 2140 ng/mL |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 4200 ng/mL |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5500 ng/mL |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 4710 ng/mL |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 6880 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 1 | 5380 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 2 | 7050 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 9 | 14300 ng/mL |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Maximum Observed Concentration (Cmax) of AMG 176 | Cycle 1 day 8 | 12700 ng/mL |
Primary
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
A DLT was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0, and considered by the investigators to be related to AMG 176. A DLT was defined as a grade 3 or higher non-hematological or a grade 4 hematologic adverse event (AE) that occurred during the DLT observation period. CTCAE is graded from grade 1 to 5, with higher grades indicating a worse outcome, and included; grade 1 = mild, grade 2= moderate, grade 3 = severe, grade 4 = life-threatening, and grade 5 = death.
Time frame: Days 1 to 28 of cycle 1 (4 weeks)
Population: DLT-evaluable analysis set included participants if they experienced a DLT during the DLT evaluation period or if they received at least 75% of the planned doses of AMG 176 (and 100% of the planned doses of azacitidine in Part 4) and completed the DLT evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 1 (AML): AMG 176 Dose D QW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 2 (AML): AMG 176 Dose E QW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 3 (AML): AMG 176 Dose E Then Dose F QW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 4 (AML): AMG 176 Dose E Then Dose G QW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 1 Participants |
Primary
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (AMG 176) up to 30 days after the end of investigational product. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests were reported as TEAEs. A treatment-related AE was any TEAE that per investigator review had a reasonable possibility of being caused by the investigational product (AMG 176).
Time frame: Day 1 cycle 1 to 30 days after the last dose of AMG 176; median treatment duration was 1.2 months
Population: The FAS included all participants that received at least 1 dose of AMG 176.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 2 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 2 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 2 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 2 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 2 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 5 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 5 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 4 Participants |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 2 Participants |
| Part 3A Cohort 4 (Japanese Participants With AML): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 2 Participants |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 2 Participants |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 3 Participants |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 2 Participants |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Participants |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 10 Participants |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 5 Participants |
| Part 4 Cohort 1 (AML): AMG 176 Dose D QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 5 Participants |
| Part 4 Cohort 1 (AML): AMG 176 Dose D QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 5 Participants |
| Part 4 Cohort 2 (AML): AMG 176 Dose E QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 4 Participants |
| Part 4 Cohort 2 (AML): AMG 176 Dose E QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 4 Cohort 3 (AML): AMG 176 Dose E Then Dose F QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 4 Participants |
| Part 4 Cohort 3 (AML): AMG 176 Dose E Then Dose F QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 4 Participants |
| Part 4 Cohort 4 (AML): AMG 176 Dose E Then Dose G QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 11 Participants |
| Part 4 Cohort 4 (AML): AMG 176 Dose E Then Dose G QW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 13 Participants |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 10 Participants |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 8 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs | 13 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 8 Participants |
Primary
Terminal Half-life (t1/2) of AMG 176
Plasma concentrations of AMG 176 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ of 5.00 ng/mL were set to zero before data analysis.
Time frame: Parts 1B, 3B, 3C, 3A (cohort 4) Cycle 1: day 1 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 8 pre, EOI; Part 3D also days 9, 15 pre and EOI; Parts 1A, 3 (except cohort 4), 4: also day 2 pre, EOI, 1, 2, 3, 5, 7 hrs EOI, day 9 pre and EOI
Population: The PK analysis set included all participants who had received at least 1 dose of AMG 176 and had at least 1 PK sample collected. Participants with data available at each time point are presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 3.33 hours |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 9.18 hours |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 7.66 hours |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 7.98 hours |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 7.43 hours |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 11.3 hours |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 1.05 hours |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 18.5 hours |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 44.5 hours |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 12.9 hours |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 16.9 hours |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 1 | 19.6 hours |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 8 | 46.7 hours |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 1 | 2.58 hours |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 8 | 28.3 hours |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 34.0 hours |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 15.3 hours |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 20.6 hours |
| Part 3A Cohort 2 (AML): AMG 176 Dose E BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 24.6 hours |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 9.81 hours |
| Part 3A Cohort 3 (AML): AMG 176 Dose E Then Dose F BIW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 6.85 hours |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 1 | 2.62 hours |
| Part 3B Cohort 1 (AML): AMG 176 Dose E QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 8 | 3.70 hours |
| Part 3B Cohort 2 (AML): AMG 176 Dose E Then Dose F QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 8 | 35.6 hours |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 8 | 11.7 hours |
| Part 3B Cohort 3 (AML): AMG 176 Dose E Then Dose G QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 1 | 47.3 hours |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 8 | 17.8 hours |
| Part 3C Cohort 1 (Japanese Participants With AML): AMG 176 Dose E QW | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 1 | 17.4 hours |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 15 | 9.08 hours |
| Part 3D Cohort 1 (AML): AMG 176 Dose D QW + Itraconazole | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 1 | 4.42 hours |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 4.33 hours |
| Part 4 Cohort 5A (AML): AMG 176 Dose E BIW + Azacitidine | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 17.7 hours |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 2 | 9.98 hours |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Terminal Half-life (t1/2) of AMG 176 | Cycle 1 day 9 | 15.4 hours |
Secondary
Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B)
A response consisted of any of the following, assessed according to the IMWG-URC: stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minor response (MR), stable disease (SD), or progressive disease (PD) per IMWG-URC. CR: negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). sCR: CR and normal serum free light chain ratio and no clonal cells in BM by immunohistochemistry. VGPR: Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-hrs). PR: ≥ 50% reduction of serum M-protein and reduction in 24-hrs urinary M-protein by ≥ 90% or to \< 200 mg/24-hours; MR: 25-49% reduction in serum M-protein and 50-89% reduction in 24-hr urinary M-protein (\>200 mg/24-hrs); SD: not meeting criteria for CR, VGPR, PR, or PD; PD: ≥ 25% increase in serum or urine M-component, BM plasma cell percentages.
Time frame: Day 1 cycle 1 to end of study; median duration from start of study treatment to end of study for all participants was 2.2 months
Population: The FAS included all participants who received at least 1 dose of AMG 176.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 3 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 3 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 4 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 2 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 1 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 3 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 1 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 1 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 4 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 1 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 3 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 1 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 2 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 2 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 5 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 3 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 1 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 1 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 1 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 1 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 1 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 1 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | VGPR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | PD | 3 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | SD | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | No post-baseline response evaluation | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | sCR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | CR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to Revised International Working Group Uniform Response Criteria (IMWG-URC) for MM Participants (Parts 1A and 1B) | MR | 0 Participants |
Secondary
Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4)
A response was of any of the following, per the ELN criteria: Complete remission (CR) without minimal residual disease (CRMRD-), CR, CR with incomplete hematology recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR), SD, PD. CRMRD-: CR with negativity for genetic marker by quantitative reverse transcription (RT-qPCR) or multicolor flow cytometry (MFC); CR: BM blasts \<5% bone marrow, no circulating blasts/ extramedullary disease, ANC \> 1.0 x 10\^9/L, platelets ≥ 100 x 10\^9/L; CRi: CR except for neutropenia (\< 1.0 x 10\^9/L) or thrombocytopenia (\< 100 x 10\^9/L); MLFS: BM blasts \< 5% no blasts with auer rods/extramedullary disease, no hematologic recovery; PR: hematological criteria of CR; decrease BM blast to 5-25%; decrease of BM blast percentage by ≤ 50%; SD: absence of CRMRD-, CR, CRi, PR, MLFS and criteria for PD not met; PD: evidence of increase in BM blast percentage and/or increase of absolute blast count.
Time frame: Day 1 cycle 1 to end of study; median duration from start of study treatment to end of study for all participants was 2.2 months
Population: The FAS included all participants who received at least 1 dose of AMG 176.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 1 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 2 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 1 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 1 Participants |
| Part 1A Cohort 1 (MM): AMG 176 Dose A BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 4 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 1 Participants |
| Part 1A Cohort 2 (MM): AMG 176 Dose B BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 3 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 0 Participants |
| Part 1A Cohort 3 (MM): AMG 176 Dose C BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 2 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 1 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 4 (MM): AMG 176 Dose D BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 1 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 3 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 1 Participants |
| Part 1A Cohort 5 (MM): AMG 176 Dose E BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 1 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 6 (MM): AMG 176 Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 2 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 1 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 1 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 7 (MM): AMG 176 Dose E Then Dose F BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 2 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 1 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 1 Participants |
| Part 1A Cohort 8 (MM): AMG 176 Dose E Then Dose G BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 2 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 3 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 7 Participants |
| Part 1A Cohort 9 (MM): AMG 176 Dose E Then Dose H BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 2 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 3 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1A Cohort 10 (MM): AMG 176 Dose E Then Dose I BIW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 1 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 3 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1B Cohort 1 (MM): AMG 176 Dose E Then Dose F QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 3 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 1 Participants |
| Part 1B Cohort 2 (MM): AMG 176 Dose E Then Dose G QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 3 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 5 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 2 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 1 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 1B Cohort 3 (MM): AMG 176 Dose E Then Dose H QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 2 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 5 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 1 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 3 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 1 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 1B Cohort 4 (MM): AMG 176 Dose E Then Dose I QW | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRMRD- | 1 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | MLFS | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CR | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | No post-baseline response evaluation | 5 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PD | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | CRi | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | PR | 0 Participants |
| Part 4 Cohort 5B (AML): AMG 176 Dose E the Dose G BIW + Azacitidine | Best Overall Response According to the 2017 European LeukemiaNet (ELN) Criteria in AML Participants (Parts 3A, 3B, 3C, 3D, and 4) | SD | 7 Participants |