Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ID: DRG0VFBIW)
| ADC Name |
AMG 224
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| Synonyms |
AMG 224; AMG224
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| Organization |
Amgen (Top20 MNC) (Originator)
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| Drug Status |
Phase 1 (discontinued)
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| Antibody Name |
Anti-human BCMA IgG1 mAb
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Antibody Info | ||||
| Antigen Name |
Tumor necrosis factor receptor superfamily member 17 (TNFRSF17)
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Antigen Info | ||||
| Payload Name |
DM1
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Payload Info | ||||
| Payload Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
4-[N-maleimidomethyl] cyclohexane-1-carboxylate (MCC)
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Linker Info | ||||
| Conjugate Type |
Random Lysines
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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 | ||
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| Multiple myeloma |
1 Trials
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General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | stable disease (SD) |
30%
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| Patients Enrolled |
Eligibility required relapsed/refractory MM after ≥3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC ≥1.0×10^9/L, platelets ≥50-75×10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenström's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone ≤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.
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| 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%
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| Patients Enrolled |
Eligibility required relapsed/refractory MM after ≥3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC ≥1.0×10^9/L, platelets ≥50-75×10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenström's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone ≤30mg/day was permitted.
Click to Show/Hide
|
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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.
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| 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
|
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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 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Partial Response (PR) |
13%
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| Patients Enrolled |
Eligibility required relapsed/refractory MM after ≥3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC ≥1.0×10^9/L, platelets ≥50-75×10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenström's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone ≤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.
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| 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%
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| Patients Enrolled |
Eligibility required relapsed/refractory MM after ≥3 prior lines (including PI+IMiD), measurable disease per IMWG, and adequate hematologic/organ function (ANC ≥1.0×10^9/L, platelets ≥50-75×10^9/L, LVEF >50%). Excluded: plasma cell leukemia/POMS/Waldenström's, recent SCT (<90 days), QTc >470ms, active CHF (NYHA class III/IV), or anti-tumor therapy within 28 days. Concurrent prednisone ≤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.
|
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| 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 % |
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| Patients Enrolled |
Relapsed or refractory (R/R) multiple myeloma (MM).
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| Administration Dosage |
Every 3 weeks (Q3W) at prespecified doses of 30-300 mg in a 3+3 design.
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| 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.
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| 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.
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| 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
