Antibody Information
General Information of This Antibody
| Antibody ID | ANI0CRHIX |
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| Antibody Name | Anti-EGFRvIII mAb |
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| Antibody Type | Monoclonal antibody (mAb) |
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| Antibody Subtype | Humanized IgG1-kappa |
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| Antigen Name | Epidermal growth factor receptor variant III (EGFRvIII) |
Antigen Info | ||||
| Click to Show/Hide the Sequence Information of This Antibody | ||||||
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
AMG 595 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | stable disease (SD) |
47%
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| Patients Enrolled |
Eligible subjects must have recurrent WHO Grade IV GBM (Parts 1-2) or Grade III AA (Part 1 only) with EGFRvIII+ expression (IHC-confirmed), Karnofsky score ≥70%, measurable disease (Macdonald criteria), and adequate organ function (ANC ≥1.5x10<sup>9</sup>/L, QTcF ≤470ms, eGFR >45 mL/min). Exclusions involve recent CNS hemorrhage (>Grade 1), significant neuropathy/ECG abnormalities, active infections, recent radiotherapy (≤12 weeks), or antiangiogenic therapy (bevacizumab within 4 weeks for Part 1; any prior use for Part 2).
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| Administration Dosage |
In this phase 1, first-in-human, open-label, sequential-dose, exploration study, adults with recurrent GBM received AMG 595 once every 3 weeks (Q3W) according to incremental dosing cohorts (0.5-3.0 mg/kg).
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| Related Clinical Trial | |||||
| NCT Number | NCT01475006 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)
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| Primary Endpoint |
The primary safety assessment includes ≥Grade 3 CTCAE-defined adverse events in lab tests, physical exams, ECGs, or vital signs evaluated 28 days post-enrollment for each cohort. PK parameters (Cmax, Cmin, t½) are analyzed across 8 timepoints over 6 weeks. Objective tumor response in GBM is assessed per Macdonald criteria over 3 years, while DLT evaluation determines the MTD at defined intervals.
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| Other Endpoint |
Secondary efficacy measures include clinical benefit rate assessed every 6 months, progression-free survival, and overall survival tracked over 3 years. Immunogenicity (anti-AMG 595 antibodies) is monitored throughout the study period.
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| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Partial Response (PR) |
6%
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| Patients Enrolled |
Eligible subjects must have recurrent WHO Grade IV GBM (Parts 1-2) or Grade III AA (Part 1 only) with EGFRvIII+ expression (IHC-confirmed), Karnofsky score ≥70%, measurable disease (Macdonald criteria), and adequate organ function (ANC ≥1.5x10<sup>9</sup>/L, QTcF ≤470ms, eGFR >45 mL/min). Exclusions involve recent CNS hemorrhage (>Grade 1), significant neuropathy/ECG abnormalities, active infections, recent radiotherapy (≤12 weeks), or antiangiogenic therapy (bevacizumab within 4 weeks for Part 1; any prior use for Part 2).
Click to Show/Hide
|
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| Administration Dosage |
In this phase 1, first-in-human, open-label, sequential-dose, exploration study, adults with recurrent GBM received AMG 595 once every 3 weeks (Q3W) according to incremental dosing cohorts (0.5-3.0 mg/kg).
|
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| Related Clinical Trial | |||||
| NCT Number | NCT01475006 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)
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| Primary Endpoint |
The primary safety assessment includes ≥Grade 3 CTCAE-defined adverse events in lab tests, physical exams, ECGs, or vital signs evaluated 28 days post-enrollment for each cohort. PK parameters (Cmax, Cmin, t½) are analyzed across 8 timepoints over 6 weeks. Objective tumor response in GBM is assessed per Macdonald criteria over 3 years, while DLT evaluation determines the MTD at defined intervals.
Click to Show/Hide
|
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| Other Endpoint |
Secondary efficacy measures include clinical benefit rate assessed every 6 months, progression-free survival, and overall survival tracked over 3 years. Immunogenicity (anti-AMG 595 antibodies) is monitored throughout the study period.
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EGFRvIII-16 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 90% | Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
ADCs were dosed at 1 and 5 mg/kg in a single dose and once weekly for 3 weeks.
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| In Vivo Model | MMT CDX model | ||||
| In Vitro Model | Malignant neoplasms of the mouse mammary gland | MMT-060562 cells | CVCL_4241 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.3 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
Cells were seeded in PDL-coated 96 well plates at 375 for MMT/hEGFRvIII, 1500 for U251/hEGFRvIII, 2000 for HEK293/hEGFRvIII, or 3000 for C4-2, PC3, and T47D cells per well in complete growth media and grown overnight.
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| In Vitro Model | Malignant neoplasms of the mouse mammary gland | MMT-060562 cells | CVCL_4241 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.3 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
Cells were seeded in PDL-coated 96 well plates at 375 for MMT/hEGFRvIII, 1500 for U251/hEGFRvIII, 2000 for HEK293/hEGFRvIII, or 3000 for C4-2, PC3, and T47D cells per well in complete growth media and grown overnight.
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| In Vitro Model | Astrocytoma | U-251MG cells | CVCL_0021 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.4 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
Cells were seeded in PDL-coated 96 well plates at 375 for MMT/hEGFRvIII, 1500 for U251/hEGFRvIII, 2000 for HEK293/hEGFRvIII, or 3000 for C4-2, PC3, and T47D cells per well in complete growth media and grown overnight.
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| In Vitro Model | Normal | HEK293 cells | CVCL_0045 | ||
EGFRvIII-MCC-DM1 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.4 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
Cells were seeded in PDL-coated 96 well plates at 375 for MMT/hEGFRvIII, 1500 for U251/hEGFRvIII, 2000 for HEK293/hEGFRvIII, or 3000 for C4-2, PC3, and T47D cells per well in complete growth media and grown overnight.
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| In Vitro Model | Normal | HEK293 cells | CVCL_0045 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
3 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
Cells were seeded in PDL-coated 96 well plates at 375 for MMT/hEGFRvIII, 1500 for U251/hEGFRvIII, 2000 for HEK293/hEGFRvIII, or 3000 for C4-2, PC3, and T47D cells per well in complete growth media and grown overnight.
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| In Vitro Model | Astrocytoma | U-251MG cells | CVCL_0021 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
10 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
Cells were seeded in PDL-coated 96 well plates at 375 for MMT/hEGFRvIII, 1500 for U251/hEGFRvIII, 2000 for HEK293/hEGFRvIII, or 3000 for C4-2, PC3, and T47D cells per well in complete growth media and grown overnight.
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| In Vitro Model | Malignant neoplasms of the mouse mammary gland | MMT-060562 cells | CVCL_4241 | ||
Homo-Ang2-Cys5.5 conjugate DAR 4 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
77.2 nM
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
ADC cell viability assay in U87EGFR-Luc (EGFRvIII+ ) and HEK293 (EGFRvIII - ) cells.
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| In Vitro Model | Glioblastoma | U87EGFR-Luc cells | CVCL_0022 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Negative EGFR vIII expression (EGFR vIII-) | ||
| Method Description |
ADC cell viability assay in U87EGFR-Luc (EGFRvIII+ ) and HEK293 (EGFRvIII - ) cells.
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| In Vitro Model | Glioblastoma | U87EGFR-Luc cells | CVCL_0022 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
80.80%
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Positive EGFR vIII expression (EGFR vIII+++/++) | ||
| Method Description |
ADC cell viability assay in U87EGFR-Luc (EGFRvIII+ ) and HEK293 (EGFRvIII - ) cells.
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| In Vitro Model | Glioblastoma | U87EGFR-Luc cells | CVCL_0022 | ||
References