General Information of This Antibody-drug Conjugate (ID: DRG0VFBIW)
ADC Name
AMG 224
Synonyms
AMG 224; AMG224
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Organization
Amgen (Top20 MNC) (Originator)
Drug Status
Phase 1 (discontinued)
Antibody Name
Anti-human BCMA IgG1 mAb
 Antibody Info 
Antigen Name
Tumor necrosis factor receptor superfamily member 17 (TNFRSF17)
 Antigen Info 
Payload Name
DM1
 Payload Info 
Payload Target
Microtubule (MT)
 Target Info 
Linker Name
4-[N-maleimidomethyl] cyclohexane-1-carboxylate (MCC)
 Linker Info 
Conjugate Type
Random Lysines
2027 Update
The disease landscape of This ADC
2027 Update
The clinical trial pipelines of This ADC
Indication Phase 1 Phase 2 Phase 3 Approved
Multiple myeloma
1 Trials
Trial ID
NCT02561962
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 6 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
stable disease (SD)  NCT02561962
PHASE1
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
progressive disease (PD)  NCT02561962
PHASE1
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
Partial Response (PR)  NCT02561962
PHASE1
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
Objective Response Rate (ORR)  NCT02561962
PHASE1
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
Objective Response Rate (ORR)  NCT02561962
Phase 1
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.
Undisclosed  NCT02561962
Phase 1
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.
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data stable disease (SD)
30%
Patients Enrolled
Eligibility required relapsed/refractory MM after &ge;3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC &ge;1.0&times;10^9/L, platelets &ge;50-75&times;10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenstr&ouml;m's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone &le;30mg/day was permitted.

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Administration Dosage
In the dose escalation, patients received intravenous AMG 224 every 3 weeks (Q3W) at prespecified doses of 30-300 mg in a 3 + 3 design, with no mandated premedications.
Related Clinical Trial
NCT Number NCT02561962  Clinical Status PHASE1
Clinical Description 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
Primary Endpoint
Dose-limiting toxicities (DLTs) were assessed during the first 28 days using CTCAE v4.0, defining hematologic DLTs as prolonged grade 4 cytopenias (neutropenia >7 days, thrombocytopenia >7 days) or grade 3+ cytopenias with complications (fever/hemorrhage), and non-hematologic DLTs as grade 3+ organ toxicities (liver/kidney), persistent GI toxicity >3 days despite therapy, or cases meeting Hy's Law criteria. Treatment-emergent AEs were monitored through Cycle 4 (12 weeks) including vital signs, labs, and neurologic assessments.

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Other Endpoint
PK parameters (Cmax, Cmin, AUC, clearance, t1/2) of AMG 224's antibody-drug conjugate (anti-BCMA-MCC-DM1) components were assessed in Cycles 1-2. Efficacy outcomes included best overall response per IMWG-URC (CR/sCR/VGPR/PR), time-to-progression, duration of response (Kaplan-Meier), MRD-negativity rate (sensitivity <1:10^5), and immunogenicity (anti-drug antibodies) over 6 years. Intensive PK sampling occurred pre/post-infusion through 336 hours.

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Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data progressive disease (PD)
15%
Patients Enrolled
Eligibility required relapsed/refractory MM after &ge;3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC &ge;1.0&times;10^9/L, platelets &ge;50-75&times;10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenstr&ouml;m's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone &le;30mg/day was permitted.

   Click to Show/Hide
Administration Dosage
In the dose escalation, patients received intravenous AMG 224 every 3 weeks (Q3W) at prespecified doses of 30-300 mg in a 3 + 3 design, with no mandated premedications.
Related Clinical Trial
NCT Number NCT02561962  Clinical Status PHASE1
Clinical Description 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
Primary Endpoint
Dose-limiting toxicities (DLTs) were assessed during the first 28 days using CTCAE v4.0, defining hematologic DLTs as prolonged grade 4 cytopenias (neutropenia >7 days, thrombocytopenia >7 days) or grade 3+ cytopenias with complications (fever/hemorrhage), and non-hematologic DLTs as grade 3+ organ toxicities (liver/kidney), persistent GI toxicity >3 days despite therapy, or cases meeting Hy's Law criteria. Treatment-emergent AEs were monitored through Cycle 4 (12 weeks) including vital signs, labs, and neurologic assessments.

   Click to Show/Hide
Other Endpoint
PK parameters (Cmax, Cmin, AUC, clearance, t1/2) of AMG 224's antibody-drug conjugate (anti-BCMA-MCC-DM1) components were assessed in Cycles 1-2. Efficacy outcomes included best overall response per IMWG-URC (CR/sCR/VGPR/PR), time-to-progression, duration of response (Kaplan-Meier), MRD-negativity rate (sensitivity <1:10^5), and immunogenicity (anti-drug antibodies) over 6 years. Intensive PK sampling occurred pre/post-infusion through 336 hours.

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Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Partial Response (PR)
13%
Patients Enrolled
Eligibility required relapsed/refractory MM after &ge;3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC &ge;1.0&times;10^9/L, platelets &ge;50-75&times;10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenstr&ouml;m's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone &le;30mg/day was permitted.

   Click to Show/Hide
Administration Dosage
In the dose escalation, patients received intravenous AMG 224 every 3 weeks (Q3W) at prespecified doses of 30-300 mg in a 3 + 3 design, with no mandated premedications.
Related Clinical Trial
NCT Number NCT02561962  Clinical Status PHASE1
Clinical Description 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
Primary Endpoint
Dose-limiting toxicities (DLTs) were assessed during the first 28 days using CTCAE v4.0, defining hematologic DLTs as prolonged grade 4 cytopenias (neutropenia >7 days, thrombocytopenia >7 days) or grade 3+ cytopenias with complications (fever/hemorrhage), and non-hematologic DLTs as grade 3+ organ toxicities (liver/kidney), persistent GI toxicity >3 days despite therapy, or cases meeting Hy's Law criteria. Treatment-emergent AEs were monitored through Cycle 4 (12 weeks) including vital signs, labs, and neurologic assessments.

   Click to Show/Hide
Other Endpoint
PK parameters (Cmax, Cmin, AUC, clearance, t1/2) of AMG 224's antibody-drug conjugate (anti-BCMA-MCC-DM1) components were assessed in Cycles 1-2. Efficacy outcomes included best overall response per IMWG-URC (CR/sCR/VGPR/PR), time-to-progression, duration of response (Kaplan-Meier), MRD-negativity rate (sensitivity <1:10^5), and immunogenicity (anti-drug antibodies) over 6 years. Intensive PK sampling occurred pre/post-infusion through 336 hours.

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Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
23%
Patients Enrolled
Eligibility required relapsed/refractory MM after &ge;3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC &ge;1.0&times;10^9/L, platelets &ge;50-75&times;10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenstr&ouml;m's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone &le;30mg/day was permitted.

   Click to Show/Hide
Administration Dosage
In the dose escalation, patients received intravenous AMG 224 every 3 weeks (Q3W) at prespecified doses of 30-300 mg in a 3 + 3 design, with no mandated premedications.
Related Clinical Trial
NCT Number NCT02561962  Clinical Status PHASE1
Clinical Description 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
Primary Endpoint
Dose-limiting toxicities (DLTs) were assessed during the first 28 days using CTCAE v4.0, defining hematologic DLTs as prolonged grade 4 cytopenias (neutropenia >7 days, thrombocytopenia >7 days) or grade 3+ cytopenias with complications (fever/hemorrhage), and non-hematologic DLTs as grade 3+ organ toxicities (liver/kidney), persistent GI toxicity >3 days despite therapy, or cases meeting Hy's Law criteria. Treatment-emergent AEs were monitored through Cycle 4 (12 weeks) including vital signs, labs, and neurologic assessments.

   Click to Show/Hide
Other Endpoint
PK parameters (Cmax, Cmin, AUC, clearance, t1/2) of AMG 224's antibody-drug conjugate (anti-BCMA-MCC-DM1) components were assessed in Cycles 1-2. Efficacy outcomes included best overall response per IMWG-URC (CR/sCR/VGPR/PR), time-to-progression, duration of response (Kaplan-Meier), MRD-negativity rate (sensitivity <1:10^5), and immunogenicity (anti-drug antibodies) over 6 years. Intensive PK sampling occurred pre/post-infusion through 336 hours.

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Experiment 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
23.00
60.00 %
Patients Enrolled
Relapsed or refractory (R/R) multiple myeloma (MM).
Administration Dosage
Every 3 weeks (Q3W) at prespecified doses of 30-300 mg in a 3+3 design.
Related Clinical Trial
NCT Number NCT02561962  Clinical Status Phase 1
Clinical Description 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.
Primary Endpoint
AmG 224 was generally well tolerated up to 190 mg Q3W.
Other Endpoint
ORR=23.00% (95% CI,11.00-39.00%), including six responses in dose escalation and three responses in the dose expansion. Two (5.00%) patients were CR and 7 (18.00%) patients were PR.
Experiment 6 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT02561962  Clinical Status Phase 1
Clinical Description 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.
References
Ref 1 A Phase 1 Study in Subjects With Relapsed or Refractory Multiple Myeloma
Ref 2 Phase 1 study of the anti-BCMA antibody-drug conjugate AMG 224 in patients with relapsed/refractory multiple myeloma. Leukemia. 2021 Jan;35(1):255-258.
Ref 3 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, NCT02561962