A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma
Sponsor
Amgen (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02561962
Collaborator
(none)
42
5
9
93.4
8.4
0.1
Study Details
Study Description
Brief Summary
This is a first in human phase 1 multicenter open label study in subjects with relapsed or refractory multiple myeloma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a first in human phase 1 multicenter open label study to evaluate the safety and tolerability of AMG 224 in subjects with relapsed or refractory multiple myeloma. The study will be conducted in 2 parts. Part 1 is the dose-exploration and part 2 is the dose-expansion. Study medication will be administered once every 3 weeks by intravenous (IV) infusion.
Study Design
Study Type:
Interventional
Actual Enrollment
:
42 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 First in Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 224 in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date
:
Nov 20, 2015
Actual Primary Completion Date
:
Nov 30, 2018
Anticipated Study Completion Date
:
Sep 1, 2023
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Exploration: AMG 224 Dose A Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Exploration: AMG 224 Dose B Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Exploration: AMG 224 Dose C Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Exploration: AMG 224 Dose D Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Exploration: AMG 224 Dose E Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Exploration: AMG 224 Dose F Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Exploration: AMG 224 Dose G Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Expansion: AMG 224 Dose H + prior CD38 targeting antibody treatment Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
| Experimental: Dose Expansion: AMG 224 Dose H + no prior CD38 targeting antibody treatment Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
Drug: AMG 224
Administered as an IV infusion.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) [Day 1 to Day 28]
Adverse events, including DLTs, were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be possibly related to AMG 224: Hematological: Grade 4 neutropenia lasting > 7 days Grade 3 or 4 neutropenia with fever > 38.5°C Grade 3 thrombocytopenia with ≥ Grade 2 hemorrhage Grade 4 thrombocytopenia lasting > 7 days Grade 3 anemia with symptoms or required intervention Grade 4 anemia Lymphopenia is not considered a DLT Non-hematological: ≥ Grade 3 nausea, vomiting or diarrhea persisting > 3 days despite optimal medical support Grade 3 fatigue persisting > 7 days ≥ Grade 3 acute kidney injury lasting > 3 days Elevation of aspartate aminotransferase or alanine aminotransferase >3x to >8x upper limit of normal (ULT) dependent on criteria Total bilirubin > 3x ULN Participants meeting the criteria for Hy's Law case were considered to have a DLT.
- Number of Participants With a Treatment-emergent Adverse Event (TEAE) [Day 1 of Cycle 1 to up to the end of Cycle 4, where each cycle is 3 weeks; up to 12 weeks.]
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that occurred after receiving at least 1 dose of treatment. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in ECGs, vital signs, physical examination with a neurologic assessment and clinical laboratory tests were recorded as TEAEs.
Secondary Outcome Measures
- Maximum Observed Concentration (Cmax) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]
Cmax of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. DM1 is a semi-synthetic derivative of the ansamycin antibiotic, maytansine conjugated to the non-cleavable linker 4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated to lysine residues in the antibody (MCC).
- Minimum Observed Concentration (Cmin) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]
Cmin of AMG 224 conjugated antibody, total anti-BCMA antibody and DM1 was measured.
- Area Under the Concentration-time Curve (AUC) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]
AUC of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.
- Clearance (CL) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]
CL of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.
- Half-life (t1/2) of AMG 224 [AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose.]
t1/2 of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured.
- Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]
BOR was the best observed post baseline disease response per IMWG-URC: Stringent Complete Response (sCR): Negative immunofixation on the serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Normal serum free light chain ratio and absence of clonal cells in BM Very Good Partial Response (PR[VGPR]): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h) PR: ≥ 50% reduction of serum M-protein and 24-hour (h) urinary M-protein by ≥ 90% or to < 200 mg/ 24-h Minor Response (MR): 25%-49% reduction of serum M-protein and 50%-89% in 24-h urinary M-protein, exceeding 200 mg/ 24-h Stable Disease (SD): Not meeting criteria above Progressive Disease (PD): ≥ 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder
- Time To Progression (TTP) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]
TTP was the time from the first administration of AMG 224 to the first objective assessment of disease progression as per IMWG-URC or deaths or if applicable date of censoring.
- Duration of Response (DOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]
DOR was defined as the time between the date of the first observation indicating an objective response as PR (or better) through to the subsequent date of disease progression as classified by per the IMWG-URC for Multiple Myeloma or death or where applicable date of censoring.
- Percentage of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]
MRD negative was defined as a tumor load of less than 1 clonal cell in 105 normal cells (as determined by flow cytometry). The percentage of participants who converted to be MRD negative was calculated.
- Number of Participants With an Anti-AMG 224 Antibody Formation [Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Pathologically documented,multiple myeloma relapsed or refractory progressive disease after at least 3 lines of therapy for multiple myeloma.
Prior therapeutic treatment or regimens must include proteasome inhibitors (e.g. bortezomib) and immunomodulatory drugs (e.g. lenalidomide).
-
Willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
-
Measurable disease per the International Myeloma Working Group (IMWG) response criteria
-
Hematological function, as follows, without transfusion support:
-
Absolute neutrophil count ≥ 1.0 X 10^9/L,
-
Platelet count ≥ 75 X 109/L (in patients with < 50% of bone marrow nucleated cells were plasma cells) or ≥ 50 X 109/L (in patients with ≥ 50% of bone marrow nucleated cells were plasma cells) without transfusion or growth factor support
-
Hemoglobin > 8 g/dL (> 80 g/L)
-
Adequate renal and hepatic function
-
Left ventricular ejection fraction (LVEF) > 50%
Exclusion Criteria:
-
Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study
-
Autologous stem cell transplant less than 90 days prior to study day 1
-
Multiple myeloma with IgM subtype
-
POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, Plasma cell leukemia, Waldenstrom's macroglobulinemia or Amyloidosis
-
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to study day
-
Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II)
-
A baseline ECG QTcF > 470 msec
-
Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 28 days prior to study day 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | West Hollywood | California | United States | 90069 |
| 2 | Research Site | Boston | Massachusetts | United States | 02114 |
| 3 | Research Site | New York | New York | United States | 10065 |
| 4 | Research Site | Houston | Texas | United States | 77030 |
| 5 | Research Site | Prahran | Victoria | Australia | 3181 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
More Information
Additional Information:
Publications
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT02561962
Other Study ID Numbers:
- 20130314
First Posted:
Sep 28, 2015
Last Update Posted:
Dec 6, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 42 participants were enrolled in the study at 4 research centers in Australia and the United States. |
|---|---|
| Pre-assignment Detail | The results reported are based on a data snapshot date of 14 March 2019. Participants are still ongoing in the study. Doses of AMG 224 in dose exploration part range from lowest in Dose A (30mg) up to highest in Dose G (250mg). Specific doses are blinded due to the protection of propriety information. |
| Arm/Group Title | Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
| Period Title: Overall Study | |||||||||
| STARTED | 3 | 3 | 3 | 3 | 6 | 6 | 5 | 11 | 2 |
| Received Treatment | 3 | 3 | 3 | 3 | 6 | 6 | 5 | 9 | 2 |
| COMPLETED | 1 | 3 | 3 | 2 | 4 | 2 | 3 | 3 | 1 |
| NOT COMPLETED | 2 | 0 | 0 | 1 | 2 | 4 | 2 | 8 | 1 |
Baseline Characteristics
| Arm/Group Title | Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose G as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 3 | 6 | 6 | 5 | 9 | 2 | 40 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||||
| Mean (Standard Deviation) [years] |
63.3
(7.0)
|
63.7
(3.8)
|
64.3
(11.2)
|
70.7
(4.0)
|
60.5
(7.1)
|
65.0
(5.7)
|
58.2
(6.0)
|
71.3
(8.7)
|
53.0
(9.9)
|
64.5
(8.4)
|
| Sex: Female, Male (Count of Participants) | ||||||||||
| Female |
1
33.3%
|
2
66.7%
|
1
33.3%
|
1
33.3%
|
3
50%
|
4
66.7%
|
4
80%
|
4
44.4%
|
1
50%
|
21
52.5%
|
| Male |
2
66.7%
|
1
33.3%
|
2
66.7%
|
2
66.7%
|
3
50%
|
2
33.3%
|
1
20%
|
5
55.6%
|
1
50%
|
19
47.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
33.3%
|
2
33.3%
|
2
40%
|
1
11.1%
|
1
50%
|
8
20%
|
| Not Hispanic or Latino |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
4
66.7%
|
4
66.7%
|
3
60%
|
8
88.9%
|
1
50%
|
32
80%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||
| Asian |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.5%
|
| Black (or African American) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
2
33.3%
|
1
20%
|
2
22.2%
|
0
0%
|
6
15%
|
| White |
0
0%
|
1
33.3%
|
2
66.7%
|
3
100%
|
4
66.7%
|
3
50%
|
3
60%
|
7
77.8%
|
2
100%
|
25
62.5%
|
| Other |
3
100%
|
2
66.7%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
20%
|
0
0%
|
0
0%
|
8
20%
|
Outcome Measures
| Title | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) |
|---|---|
| Description | Adverse events, including DLTs, were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. A DLT was considered as any of the below, if judged by the investigator to be possibly related to AMG 224: Hematological: Grade 4 neutropenia lasting > 7 days Grade 3 or 4 neutropenia with fever > 38.5°C Grade 3 thrombocytopenia with ≥ Grade 2 hemorrhage Grade 4 thrombocytopenia lasting > 7 days Grade 3 anemia with symptoms or required intervention Grade 4 anemia Lymphopenia is not considered a DLT Non-hematological: ≥ Grade 3 nausea, vomiting or diarrhea persisting > 3 days despite optimal medical support Grade 3 fatigue persisting > 7 days ≥ Grade 3 acute kidney injury lasting > 3 days Elevation of aspartate aminotransferase or alanine aminotransferase >3x to >8x upper limit of normal (ULT) dependent on criteria Total bilirubin > 3x ULN Participants meeting the criteria for Hy's Law case were considered to have a DLT. |
| Time Frame | Day 1 to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT analysis set: all participants who are DLT evaluable. A participant was not DLT-evaluable if the participant discontinued treatment for any reason other than a DLT prior to completing the first 28 days of AMG 224 treatment or did not receive 2 doses of AMG 224 during the 28-day DLT window. |
| Arm/Group Title | Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
| Measure Participants | 3 | 3 | 3 | 3 | 3 | 6 | 4 | 8 | 1 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
3
60%
|
0
0%
|
0
0%
|
| Title | Number of Participants With a Treatment-emergent Adverse Event (TEAE) |
|---|---|
| Description | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that occurred after receiving at least 1 dose of treatment. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in ECGs, vital signs, physical examination with a neurologic assessment and clinical laboratory tests were recorded as TEAEs. |
| Time Frame | Day 1 of Cycle 1 to up to the end of Cycle 4, where each cycle is 3 weeks; up to 12 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set: all participants that are enrolled and received at least 1 dose of AMG 224. |
| Arm/Group Title | Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. |
| Measure Participants | 3 | 3 | 3 | 3 | 6 | 6 | 5 | 9 | 2 |
| TEAE |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
6
100%
|
6
100%
|
5
100%
|
9
100%
|
2
100%
|
| Treatment-related TEAE |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
5
83.3%
|
5
83.3%
|
5
100%
|
7
77.8%
|
1
50%
|
| Title | Maximum Observed Concentration (Cmax) of AMG 224 |
|---|---|
| Description | Cmax of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. DM1 is a semi-synthetic derivative of the ansamycin antibiotic, maytansine conjugated to the non-cleavable linker 4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated to lysine residues in the antibody (MCC). |
| Time Frame | AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Minimum Observed Concentration (Cmin) of AMG 224 |
|---|---|
| Description | Cmin of AMG 224 conjugated antibody, total anti-BCMA antibody and DM1 was measured. |
| Time Frame | AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Area Under the Concentration-time Curve (AUC) of AMG 224 |
|---|---|
| Description | AUC of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. |
| Time Frame | AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Clearance (CL) of AMG 224 |
|---|---|
| Description | CL of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. |
| Time Frame | AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Half-life (t1/2) of AMG 224 |
|---|---|
| Description | t1/2 of AMG 224 conjugated antibody, total anti-B-cell maturation antigen (anti-BCMA) antibody and DM1 was measured. |
| Time Frame | AMG 224: Cycles 1-4 (each cycle = 3 weeks): pre-dose and 0 to 336 hours post-dose; Cycles 5 onwards: pre-dose to 37 days post last dose. DM1: Cycles 1-2 only: pre-dose and 0 to 96 hours post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) |
|---|---|
| Description | BOR was the best observed post baseline disease response per IMWG-URC: Stringent Complete Response (sCR): Negative immunofixation on the serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Normal serum free light chain ratio and absence of clonal cells in BM Very Good Partial Response (PR[VGPR]): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h) PR: ≥ 50% reduction of serum M-protein and 24-hour (h) urinary M-protein by ≥ 90% or to < 200 mg/ 24-h Minor Response (MR): 25%-49% reduction of serum M-protein and 50%-89% in 24-h urinary M-protein, exceeding 200 mg/ 24-h Stable Disease (SD): Not meeting criteria above Progressive Disease (PD): ≥ 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder |
| Time Frame | Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time To Progression (TTP) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) |
|---|---|
| Description | TTP was the time from the first administration of AMG 224 to the first objective assessment of disease progression as per IMWG-URC or deaths or if applicable date of censoring. |
| Time Frame | Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Duration of Response (DOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) |
|---|---|
| Description | DOR was defined as the time between the date of the first observation indicating an objective response as PR (or better) through to the subsequent date of disease progression as classified by per the IMWG-URC for Multiple Myeloma or death or where applicable date of censoring. |
| Time Frame | Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity |
|---|---|
| Description | MRD negative was defined as a tumor load of less than 1 clonal cell in 105 normal cells (as determined by flow cytometry). The percentage of participants who converted to be MRD negative was calculated. |
| Time Frame | Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants With an Anti-AMG 224 Antibody Formation |
|---|---|
| Description | |
| Time Frame | Day 1 of Cycle 1 to up to the end of study (up to 37 days after the last dose), where each cycle is 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Day 1 of Cycle 1 to end of Cycle 4 (where each cycle is 3 weeks); a maximum of 12 weeks. | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold of 5%. | |||||||||||||||||
| Arm/Group Title | Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment | |||||||||
| Arm/Group Description | Participants were administered AMG 224 Dose A as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose B as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose C as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose D as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose E as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose F as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants were administered AMG 224 Dose G as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the maximum tolerated dose [MTD] identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | Participants who had no prior treatment with CD38-targeting antibody were administered AMG 224 Dose H (the MTD identified based on the dose exploration phase) as an IV infusion Q3W on Day 1 of each cycle, where each cycle is 3 weeks. | |||||||||
All Cause Mortality |
||||||||||||||||||
| Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/11 (0%) | 0/2 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/3 (66.7%) | 2/6 (33.3%) | 2/6 (33.3%) | 2/5 (40%) | 6/9 (66.7%) | 0/2 (0%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Febrile neutropenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Neutropenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Plasma cell disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Thrombocytopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Atrial flutter | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Nausea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| General disorders | ||||||||||||||||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hepatobiliary disorders | ||||||||||||||||||
| Cholecystitis acute | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Acute sinusitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Influenza | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Lower respiratory tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Parainfluenzae virus infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Pneumonia pneumococcal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Clavicle fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Fall | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Femur fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Infusion related reaction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Spinal fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Dehydration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Failure to thrive | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Fluid overload | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Back pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Osteitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Pathological fracture | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||
| Plasmacytoma | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Facial paralysis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Dyspnoea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Dose Exploration: AMG 224 Dose A | Dose Exploration: AMG 224 Dose B | Dose Exploration: AMG 224 Dose C | Dose Exploration: AMG 224 Dose D | Dose Exploration: AMG 224 Dose E | Dose Exploration: AMG 224 Dose F | Dose Exploration: AMG 224 Dose G | Dose Expansion: AMG 224 Dose H + Prior CD38 Targeting Antibody Treatment | Dose Expansion: AMG 224 Dose H + no Prior CD38 Targeting Antibody Treatment | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 5/6 (83.3%) | 6/6 (100%) | 5/5 (100%) | 7/9 (77.8%) | 2/2 (100%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 3/6 (50%) | 5/6 (83.3%) | 3/5 (60%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Leukopenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Neutropenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/9 (22.2%) | 1/2 (50%) | |||||||||
| Splenic lesion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Splenomegaly | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Thrombocytopenia | 2/3 (66.7%) | 3/3 (100%) | 2/3 (66.7%) | 2/3 (66.7%) | 1/6 (16.7%) | 5/6 (83.3%) | 3/5 (60%) | 6/9 (66.7%) | 1/2 (50%) | |||||||||
| Thrombocytosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Palpitations | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Tachycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Ear and labyrinth disorders | ||||||||||||||||||
| Tinnitus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Vertigo positional | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Eye disorders | ||||||||||||||||||
| Conjunctival haemorrhage | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Diplopia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Dry eye | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Eye irritation | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Eye pruritus | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Lacrimation increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Ocular hyperaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Vision blurred | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Visual acuity reduced | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Visual impairment | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Vitreous haemorrhage | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Abdominal distension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Abdominal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Abdominal pain upper | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Constipation | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Diarrhoea | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/6 (50%) | 1/6 (16.7%) | 0/5 (0%) | 4/9 (44.4%) | 0/2 (0%) | |||||||||
| Dry mouth | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Flatulence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Gingival bleeding | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Nausea | 2/3 (66.7%) | 2/3 (66.7%) | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 4/6 (66.7%) | 2/5 (40%) | 2/9 (22.2%) | 1/2 (50%) | |||||||||
| Oral disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Oral pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Stomatitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 2/9 (22.2%) | 1/2 (50%) | |||||||||
| Toothache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Vomiting | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| General disorders | ||||||||||||||||||
| Asthenia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Chills | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Fatigue | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 3/3 (100%) | 3/6 (50%) | 4/6 (66.7%) | 0/5 (0%) | 6/9 (66.7%) | 0/2 (0%) | |||||||||
| Infusion site bruising | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Malaise | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Mucosal inflammation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Oedema peripheral | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Pain | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/6 (33.3%) | 2/6 (33.3%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Hepatobiliary disorders | ||||||||||||||||||
| Cholecystitis acute | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Beta haemolytic streptococcal infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Cellulitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Ear infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Folliculitis | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Gastroenteritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Gastrointestinal candidiasis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Herpes ophthalmic | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hordeolum | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Influenza | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Lower respiratory tract infection | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Nasopharyngitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Oral candidiasis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 1/2 (50%) | |||||||||
| Otitis externa | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Picornavirus infection | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Respiratory tract infection | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Respiratory tract infection viral | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Rhinitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Upper respiratory tract infection | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Urinary tract infection staphylococcal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Viral upper respiratory tract infection | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Contusion | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Foot fracture | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Skin abrasion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Skin laceration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Skin wound | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Stress fracture | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Wound | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Alanine aminotransferase increased | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 3/6 (50%) | 2/5 (40%) | 3/9 (33.3%) | 1/2 (50%) | |||||||||
| Aspartate aminotransferase increased | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 4/6 (66.7%) | 2/5 (40%) | 4/9 (44.4%) | 1/2 (50%) | |||||||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 3/5 (60%) | 2/9 (22.2%) | 0/2 (0%) | |||||||||
| Blood creatine increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Blood creatinine decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Blood creatinine increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Blood potassium decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Blood urea increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 2/9 (22.2%) | 0/2 (0%) | |||||||||
| Calcium ionised increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Coagulation time prolonged | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Gamma-glutamyltransferase increased | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Haemoglobin decreased | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Lymphocyte count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Weight decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| White blood cell count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/6 (33.3%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Decreased appetite | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 3/9 (33.3%) | 0/2 (0%) | |||||||||
| Hyperalbuminaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hypercalcaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/5 (20%) | 4/9 (44.4%) | 0/2 (0%) | |||||||||
| Hyperglycaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 3/6 (50%) | 1/5 (20%) | 3/9 (33.3%) | 1/2 (50%) | |||||||||
| Hypermagnesaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hypernatraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Hyperuricaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hypoalbuminaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Hypoglycaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hypomagnesaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/6 (16.7%) | 2/6 (33.3%) | 2/5 (40%) | 2/9 (22.2%) | 0/2 (0%) | |||||||||
| Hyponatraemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Iron deficiency | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/5 (0%) | 3/9 (33.3%) | 1/2 (50%) | |||||||||
| Arthritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Back pain | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 2/9 (22.2%) | 1/2 (50%) | |||||||||
| Bone pain | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Groin pain | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Joint swelling | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Muscle spasms | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Muscular weakness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Musculoskeletal chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Musculoskeletal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Musculoskeletal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 4/9 (44.4%) | 1/2 (50%) | |||||||||
| Musculoskeletal stiffness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Myalgia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/5 (0%) | 4/9 (44.4%) | 1/2 (50%) | |||||||||
| Pain in extremity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Tendonitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 1/2 (50%) | |||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||
| Plasmacytoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Dizziness | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/6 (0%) | 2/6 (33.3%) | 1/5 (20%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Dysgeusia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Headache | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 1/5 (20%) | 1/9 (11.1%) | 2/2 (100%) | |||||||||
| Hypoaesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Memory impairment | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Neuropathy peripheral | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Paraesthesia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Peripheral sensory neuropathy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Tremor | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Psychiatric disorders | ||||||||||||||||||
| Agitation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Depression | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Insomnia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Restlessness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 1/2 (50%) | |||||||||
| Sleep disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Stress | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Chromaturia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Haematuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Urinary incontinence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Urinary retention | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Cough | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/5 (0%) | 2/9 (22.2%) | 1/2 (50%) | |||||||||
| Dyspnoea | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 3/9 (33.3%) | 1/2 (50%) | |||||||||
| Epistaxis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hiccups | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Nasal congestion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Nasal dryness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Oropharyngeal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Paranasal sinus discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 1/2 (50%) | |||||||||
| Productive cough | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Rhinorrhoea | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Alopecia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Erythema | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hyperhidrosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Night sweats | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Pruritus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Rash | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Rash generalised | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Rosacea | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Skin hyperpigmentation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Skin induration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Skin lesion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 1/2 (50%) | |||||||||
| Surgical and medical procedures | ||||||||||||||||||
| Cholecystectomy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/9 (11.1%) | 0/2 (0%) | |||||||||
| Skin neoplasm excision | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Vascular disorders | ||||||||||||||||||
| Flushing | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hot flush | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hypertension | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/5 (20%) | 0/9 (0%) | 0/2 (0%) | |||||||||
Limitations/Caveats
Results reported are as of the data snapshot date of March 2019. The study is ongoing.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT02561962
Other Study ID Numbers:
- 20130314
First Posted:
Sep 28, 2015
Last Update Posted:
Dec 6, 2021
Last Verified:
Dec 1, 2021