Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00062
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| PDC Name |
ANG1005
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| Synonyms |
Paclitaxel trevatide; CHEMBL1089636; ANG1005; ANG-1005
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| PDC Status |
Phase 3
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| Indication |
In total 1 Indication(s)
Breast cancer
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| Structure |
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| Peptide Name |
Angiopep-2
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Peptide Info | ||||
| Receptor Name |
Prolow-density lipoprotein receptor-related protein 1; Low-density lipoprotein receptor-related protein 2 (LRP1; LRP2)
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Receptor Info | ||||
| Drug Name |
Paclitaxel
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Drug Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Succinic Acid
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Linker Info | ||||
| Drugbank ID | ||||||
| ChEBI ID | ||||||
| Formula |
C257H308N32O79
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| #Ro5 Violations (Lipinski): 4 | Molecular Weight | 5109 | ||||
| Lipid-water partition coefficient (xlogp) | 3.6 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 46 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 81 | |||||
| Rotatable Bond Count (rotbonds) | 138 | |||||
Full List of Activity Data of This Peptide-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | 3-month progression-free survival rate |
52.00%
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| Patients Enrolled |
Adult patients with measurable recurrent brain metastases from breast cancer.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
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| Description |
Investigator assessments resulted in median intracranial PFS of 2.8 months and the 3-month intracranial PFS rate was 52%.
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| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | 3-month progression-free survival rate |
54.00%
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| Patients Enrolled |
Patients with leptomeningeal carcinomatosis.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
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| Description |
The investigator determined intracranial median PFS was 2.8 months and the 3-month PFS rate was 54% (Table 3). Median duration of response was 18 weeks (7.3-26.3).
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| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | 6-month progression-free survival rate |
18.70%
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| Patients Enrolled |
Adult patients with measurable recurrent brain metastases from breast cancer.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
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| Description |
Investigator assessments resulted in median intracranial PFS of 2.8 months and the 3-month intracranial PFS rate was 52%.
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| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Clinical benefit rate (CBR) |
67%
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| Patients Enrolled |
Patients with leptomeningeal carcinomatosis.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
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| Description |
Investigator determined ORR was 29% and the iCBR was 67%.
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| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Clinical benefit rate (CBR) |
68%
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| Patients Enrolled |
Adult patients with measurable recurrent brain metastases from breast cancer.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
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| Description |
On the basis of the CNS tumor response assessment, performed by local investigators, there were nine (15%) evaluable patients with PR including five (8%) confirmed PR (to confirm PR, it was required that the response was sustained for ≥4 weeks), and 32 (53%) evaluable patients with SD, resulting in an overall iORR of 15% and iCBR of 68%.
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| Experiment 6 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Median duration of response |
18 weeks
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| Patients Enrolled |
Patients with leptomeningeal carcinomatosis.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
|
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| Description |
The investigator determined intracranial median PFS was 2.8 months and the 3-month PFS rate was 54% (Table 3). Median duration of response was 18 weeks (7.3-26.3).
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| Experiment 7 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Median progression-free survival (mPFS) |
2.8 months
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| Patients Enrolled |
Patients with leptomeningeal carcinomatosis.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
|
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| Description |
The investigator determined intracranial median PFS was 2.8 months and the 3-month PFS rate was 54% (Table 3). Median duration of response was 18 weeks (7.3-26.3).
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| Experiment 8 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Median progression-free survival (mPFS) |
12.1 weeks
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| Patients Enrolled |
Adult patients with measurable recurrent brain metastases from breast cancer.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
|
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| Description |
Investigator assessments resulted in median intracranial PFS of 2.8 months and the 3-month intracranial PFS rate was 52%.
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| Experiment 9 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Objective response rate (ORR) |
15%
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| Patients Enrolled |
Adult patients with measurable recurrent brain metastases from breast cancer.
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
|
||||
| Description |
On the basis of the CNS tumor response assessment, performed by local investigators, there were nine (15%) evaluable patients with PR including five (8%) confirmed PR (to confirm PR, it was required that the response was sustained for ≥4 weeks), and 32 (53%) evaluable patients with SD, resulting in an overall iORR of 15% and iCBR of 68%.
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| Experiment 10 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Objective response rate (ORR) |
29%
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| Patients Enrolled |
Patients with leptomeningeal carcinomatosis.
|
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| Administration Time | Every 3 weeks | ||||
| Administration Dosage | 600 mg/m2 | ||||
| MOA of PDC |
Because LRP1 is also expressed on tumor cells in both CNS and systemic metastases, ANG1005 gains entry via LRP1 mediated endocytosis, where paclitaxel is cleaved from the peptide backbone by lysosomal esterases.
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| Description |
Investigator determined ORR was 29% and the iCBR was 67%.
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References