Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ID: DRG0LODVW)
| ADC Name |
MEDI-547
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| Synonyms |
MEDI-547
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| Organization |
MedImmune (Top20 MNC) (Originator)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
4
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| Structure |
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| Antibody Name |
Anti-EPHA2 (1C1) mAb
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Antibody Info | ||||
| Antigen Name |
Ephrin type-A receptor 2 (EPHA2)
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Antigen Info | ||||
| Payload Name |
Monomethyl auristatin F
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Payload Info | ||||
| Payload Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Maleimido-caproyl
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
mafodotin
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2027 Update
The disease landscape of This ADC
2027 Update
The clinical trial pipelines of This ADC
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Discovered Using Cell Line-derived Xenograft Model
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) |
16.70%
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| Patients Enrolled |
Eligible patients must have relapsed/refractory solid tumors (ovarian, prostate, NSCLC, etc.) with prior histologic confirmation, ECOG 0-2, adequate organ function, and measurable disease (for dose expansion). Exclusions include uncontrolled CNS metastases, active infections, significant cardiac history, recent stroke/TIA, uncontrolled hypertension, anticoagulant use, and pregnancy/lactation. Prior therapies must be completed ≥30 days before enrollment.
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| Administration Dosage |
All 6 patients were exposed to MEDI-547 at a dose of 0.08 mg/kg once every 3 weeks.
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| Related Clinical Trial | |||||
| NCT Number | NCT00796055 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1, Open-Label Study of MEDI-547 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Biologic Activity of Intravenous Administration in Subjects With Relapsed or Refractory Solid Tumors Associated With EphA2 Expression | ||||
| Primary Endpoint |
The safety and tolerability of MEDI-547 will be evaluated through monitoring adverse events (AEs), serious AEs (SAEs), lab abnormalities, physical exam changes, treatment discontinuations due to toxicity, and drug-related deaths during treatment and up to 30 days post-treatment.
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| Other Endpoint |
Antitumor activity will be assessed via objective response rate (ORR), time to response (TTR), duration of response (DR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS), with measurements continuing until 30 days after the last MEDI-547 dose.
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| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | progressive disease (PD) |
83.30%
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| Patients Enrolled |
Eligible patients must have relapsed/refractory solid tumors (ovarian, prostate, NSCLC, etc.) with prior histologic confirmation, ECOG 0-2, adequate organ function, and measurable disease (for dose expansion). Exclusions include uncontrolled CNS metastases, active infections, significant cardiac history, recent stroke/TIA, uncontrolled hypertension, anticoagulant use, and pregnancy/lactation. Prior therapies must be completed ≥30 days before enrollment.
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| Administration Dosage |
All 6 patients were exposed to MEDI-547 at a dose of 0.08 mg/kg once every 3 weeks.
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| Related Clinical Trial | |||||
| NCT Number | NCT00796055 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1, Open-Label Study of MEDI-547 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Biologic Activity of Intravenous Administration in Subjects With Relapsed or Refractory Solid Tumors Associated With EphA2 Expression | ||||
| Primary Endpoint |
The safety and tolerability of MEDI-547 will be evaluated through monitoring adverse events (AEs), serious AEs (SAEs), lab abnormalities, physical exam changes, treatment discontinuations due to toxicity, and drug-related deaths during treatment and up to 30 days post-treatment.
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| Other Endpoint |
Antitumor activity will be assessed via objective response rate (ORR), time to response (TTR), duration of response (DR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS), with measurements continuing until 30 days after the last MEDI-547 dose.
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| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
0%
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| Patients Enrolled |
Malignant solid tumor thought to be associated with increased expression of EphA2 (endometrial, breast, ovarian, prostate, non-small cell lung, colon, esophageal, gastric, and bladder cancers, renal cell carcinoma, melanoma), relapsed or refractory to standard therapy, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
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| Administration Dosage |
0.08 mg/kg, 1-h intravenous (IV) infusion once q3wks or qwk for 3 consecutive weeks until unacceptable toxicity, progressive disease.
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| Related Clinical Trial | |||||
| NCT Number | NCT00796055 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, open-label study of MEDI-547 to evaluate the safety, tolerability, pharmacokinetics, and biologic activity of intravenous administration in subjects with relapsed or refractory solid tumors associated with epha2 expression. | ||||
| Primary Endpoint |
Best response included progressive disease (n=5, 83.33%) and stable disease (n=1, 16.67%), No complete or partial tumor responses.
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| Other Endpoint |
MTD could not be selected.
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Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 48% | Negative EPHA2 expression (EPHA2-) | ||
| Method Description |
Mice injected with EphA2-negative SPEC-2 cell was assigned to one of four groups (n = 10 mice per group),MEDI-547,3 mg/kg weekly.
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| In Vivo Model | Endometrial cancer CDX model | ||||
| In Vitro Model | Endometrial cancer | Endometrial cancer cells | Homo sapiens | ||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 86.67% | Positive EPHA2 expression (EPHA2+++/++) | ||
| Method Description |
Mice injected with either Hec-1A or Ishikawa were assigned to one of four groups (n = 10 mice per group),MEDI-547,3 mg/kg weekly.
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| In Vivo Model | Endometrial cancer CDX model | ||||
| In Vitro Model | Endometrial adenocarcinoma | HEC-1-A cells | CVCL_0293 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 92% | Positive EPHA2 expression (EPHA2+++/++) | ||
| Method Description |
Mice injected with either Hec-1A or Ishikawa were assigned to one of four groups (n = 10 mice per group),MEDI-547,3 mg/kg weekly.
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| In Vivo Model | Endometrial cancer CDX model | ||||
| In Vitro Model | Endometrial adenocarcinoma | Ishikawa cells | CVCL_2529 | ||
References