Phase 1
N=42
A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma
Multiple Myeloma
Bottom Line
View on ClinicalTrials.gov: NCT02561962 ↗Enrolled (actual)
42
Serious AEs
37.5%
Results posted
Oct 2021
Primary outcome: Primary: Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- AMG 224 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Nov 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With a Treatment-emergent Adverse Event (TEAE) |
3; 3; 3; 3; 6; 6 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of AMG 224 Conjugated Antibody, Total Anti-B-cell Maturation Antigen (Anti-BCMA) Antibody, and Total Unconjugated DM1 |
11.4; 22.0; 25.3; 32.9; 37.5; 54.2 | — |
| SECONDARY Minimum Observed Concentration (Cmin) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1 |
1.45; 2.81; 4.54; 4.40; 3.51; 10.5 | — |
| SECONDARY Area Under the Concentration-time Curve (AUC) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1 |
1850; 3450; 4520; 5260; 3710; 10400 | — |
| SECONDARY Clearance (CL) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1 |
17.7; 17.9; 20.1; 27.2; 47.0; 18.8 | — |
| SECONDARY Terminal Half-life (t1/2,z) of AMG 224 Conjugated Antibody, Total Anti-BCMA Antibody, and Total Unconjugated DM1 |
217; 218; 278; 196; 139; 189 | — |
| SECONDARY Best Overall Response (BOR) According to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) |
0; 0; 0; 1; 0; 1 | — |
| SECONDARY Time To Progression (TTP) According to IMWG-URC |
74.9; 1.6; 1.4; 3.7; 14.0; 2.3 | — |
| SECONDARY Duration of Response (DOR) According to IMWG-URC |
63.1; NA; NA; 60.8; 9.1; 19.2 | — |
| SECONDARY Number of Participants With Conversion to Minimal Residual Disease (MRD)-Negativity |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Anti-AMG 224 Antibodies |
0; 0; 0; 0; 0; 2 | — |
Summary
This is a first in human phase 1 multicenter open label study in subjects with relapsed or refractory multiple myeloma.
Eligibility Criteria
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 10^9/L (in patients with 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
Data sourced from ClinicalTrials.gov (NCT02561962). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.