Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0JUOLN
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| ADC Name |
BMS-936561
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| Synonyms |
BMS-936561; MDX-1203
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| Organization |
Medarex (Top20 MNC) (Originator)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
2
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| Structure |
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| Antibody Name |
MDX-1115
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Antibody Info | ||||
| Antigen Name |
CD70 antigen (CD70)
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Antigen Info | ||||
| Payload Name |
seco-MED-A
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Payload Info | ||||
| Therapeutic Target |
Human deoxyribonucleic acid (hDNA)
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Target Info | ||||
| Linker Name |
Mal-Val-Cit
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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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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| Kidney cancer |
1 Trials
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| Unspecific non-hodgkin lymphoma |
1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Maximum Observed Concentration (Cmax) | 45 | nM |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 0.5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4.1 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 0.5 mg/kg.
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[1] |
| Maximum Observed Concentration (Cmax) | 185 | nM |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 1 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 0.6 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 1 mg/kg.
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[1] |
| Maximum Observed Concentration (Cmax) | 269 | nM |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 10 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 2 mg/kg.
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[1] |
| Maximum Observed Concentration (Cmax) | 452 | nM |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 4 mg/kg.
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[1] |
| Maximum Observed Concentration (Cmax) | 1073 | nM |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 74 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Maximum Observed Concentration (Cmax) | 1638 | nM |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 73 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 4.1 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 0.5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 0.6 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 1 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 10 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 74 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 73 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 4.1 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 0.5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 0.6 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 1 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 10 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 74 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 73 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 4.1 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 0.5 mg/kg.
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[1] |
| Elimination Half-Life (t1/2) | 4.3 | day |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 0.5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 0.6 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 1 mg/kg.
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[1] |
| Elimination Half-Life (t1/2) | 4.3 | day |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 1 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 10 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 2 mg/kg.
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[1] |
| Elimination Half-Life (t1/2) | 3.1 | day |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 4 mg/kg.
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[1] |
| Elimination Half-Life (t1/2) | 6.2 | day |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 74 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Elimination Half-Life (t1/2) | 4.4 | day |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 73 | uM*h |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
| Elimination Half-Life (t1/2) | 3.4 | day |
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70, 8 mg/kg.
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[1] |
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 | [2] | ||||
| Efficacy Data | stable disease (SD) |
69%
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| Patients Enrolled |
Eligible patients must have ECOG 0-2 and meet tumor-specific criteria: ccRCC patients must have advanced/recurrent disease failing ≥1 prior therapy; B-NHL patients must have relapsed/refractory disease failing ≥1 prior therapy. All subjects must have measurable disease (unidimensional for ccRCC, bidimensional for B-NHL) and provide CD70+ tumor tissue (archived/fresh). Key exclusions include prior anti-CD70 therapy, severe mAb hypersensitivity, active CNS lymphoma, infections, bleeding disorders, active autoimmune disease requiring immunosuppression, or substance abuse.
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| Administration Dosage |
Assigned Interventions: Single dose of MDX-1203 will be administered every 21 days as an intravenous (i.v.) infusion. Subjects will receive one dose of MDX-1203.
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| Related Clinical Trial | |||||
| NCT Number | NCT00944905 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I, Multicenter, Open-Label, Dose-Escalation, Multidose Study of MDX-1203 in Subjects With Advanced/Recurrent Clear Cell Renal Cell Carcinoma or Relapsed/Refractory B-Cell Non Hodgkin's Lymphoma | ||||
| Primary Endpoint |
The study evaluates the safety profile of MDX-1203 and determines the maximum tolerated dose (MTD) with assessment conducted over up to 17 treatment cycles.
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| Other Endpoint |
Biomarker analysis includes assessment of CD70+ tumor incidence in the target population, evaluated during the screening phase.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT00944905 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label, dose-escalation, multidose study of MDX-1203 in subjects with advanced/recurrent clear cell renal cell carcinoma or relapsed/refractory B-cell non Hodgkin's lymphoma. | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Advanced or recurrent clear cell renal cell carcinoma (ccRCC) or relapsed or refractory B-non Hodgkin lymphoma (NHL), life expectancy of 12 weeks; ECOG performance status of 0-2; measurable disease by RECIST 1.1 criteria for ccRCC and by IWG 2007 criteria for B-NHL as well as adequate hematologic, renal and liver function parameters.
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| Administration Dosage |
0.50, 1.00, 2.00, 4.00, 8.00, 15.00 mg/kg administered every 21 days in a 42 day cycle for a maximum of 17 cycles, IV.
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| Related Clinical Trial | |||||
| NCT Number | NCT00944905 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label, dose-escalation, multidose study of MDX-1203 in subjects with advanced/recurrent clear cell renal cell carcinoma or relapsed/refractory B-cell non Hodgkin's lymphoma. | ||||
| Primary Endpoint |
The highest best tolerated dose and the recommended dose for future studies was 8 mg/kg dose.There was no MTD determined during the acute toxicity assessment window according to protocol-defined DLT according to protocol-defined DLT. There was disease stabilization in 18 of 26 patients (69.23%) without correlation with received dose.
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References