Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0LODVW
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| 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 |
MMAF
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Payload Info | ||||
| Therapeutic 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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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||
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| Unspecific solid tumor |
1 Trials
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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