Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0XPPOZ
|
|||||
|---|---|---|---|---|---|---|
| ADC Name |
Vorsetuzumab mafodotin
|
|||||
| Synonyms |
vorsetuzumab mafodotin; SGN-75; h1F6; vorsetuzumab
Click to Show/Hide
|
|||||
| Organization |
Seagen (Top20 MNC) (Originator)
|
|||||
| Drug Status |
Phase 1 (discontinued)
|
|||||
| Drug-to-Antibody Ratio |
3 to 4
|
|||||
| Structure |
|
|||||
|
|
||||||
| Antibody Name |
Vorsetuzumab
|
Antibody Info | ||||
| Antigen Name |
CD70 antigen (CD70)
|
Antigen Info | ||||
| Payload Name |
MMAF
|
Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
|
Target Info | ||||
| Linker Name |
Maleimido-caproyl
|
Linker Info | ||||
| Conjugate Type |
Random Cysteines
|
|||||
| Combination Type |
mafodotin
|
|||||
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 | ||
|---|---|---|---|---|---|---|---|---|---|
| Kidney cancer |
1 Trials
|
||||||||
| Unspecific non-hodgkin lymphoma |
1 Trials
|
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 25 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 28 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 190 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 240 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 200 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 170 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 400 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 510 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 550 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 760 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUCinf.
|
[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 25 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 28 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUCinf.
|
[1] |
| End-of-Infusion Concentration (Ceoi) | 4 | ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg.
|
[1] |
| Volume of Distribution (Vd) | 89 | mL/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUCinf.
|
[1] |
| End-of-Infusion Concentration (Ceoi) | 20 | ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg.
|
[1] |
| Volume of Distribution (Vd) | 88 | mL/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 190 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 240 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUCinf.
|
[1] |
| End-of-Infusion Concentration (Ceoi) | 26 | ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg.
|
[1] |
| Volume of Distribution (Vd) | 83 | mL/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 200 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 170 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUCinf.
|
[1] |
| End-of-Infusion Concentration (Ceoi) | 40 | ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg.
|
[1] |
| Volume of Distribution (Vd) | 100 | mL/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 400 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 510 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUCinf.
|
[1] |
| End-of-Infusion Concentration (Ceoi) | 66 | ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg.
|
[1] |
| Volume of Distribution (Vd) | 75 | mL/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 550 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 760 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUCinf.
|
[1] |
| End-of-Infusion Concentration (Ceoi) | 88 | ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg.
|
[1] |
| Volume of Distribution (Vd) | 91 | mL/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg.
|
[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 25 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 28 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 190 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 240 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 200 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 170 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 400 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 510 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUCinf.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 550 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 760 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUCinf.
|
[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 25 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 28 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg, AUCinf.
|
[1] |
| Elimination Half-Life (t1/2) | 6 | day |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg.
|
[1] |
| Clearance (CL) | 11 | mL/day/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 0.3 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 110 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg, AUCinf.
|
[1] |
| Elimination Half-Life (t1/2) | 9.7 | day |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg.
|
[1] |
| Clearance (CL) | 8.9 | mL/day/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.0 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 190 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 240 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg, AUCinf.
|
[1] |
| Elimination Half-Life (t1/2) | 9.6 | day |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg.
|
[1] |
| Clearance (CL) | 6.1 | mL/day/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 1.5 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 200 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 170 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg, AUCinf.
|
[1] |
| Elimination Half-Life (t1/2) | 6.8 | day |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg.
|
[1] |
| Clearance (CL) | 11 | mL/day/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 2.0 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 400 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 510 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg, AUCinf.
|
[1] |
| Elimination Half-Life (t1/2) | 10 | day |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg.
|
[1] |
| Clearance (CL) | 5.8 | mL/day/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 3.0 mg/kg.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 550 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUC0-21d.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 760 | day*ug/mL |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg, AUCinf.
|
[1] |
| Elimination Half-Life (t1/2) | 11 | day |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg.
|
[1] |
| Clearance (CL) | 5.9 | mL/day/kg |
First-dose pk parameters for SGN-75 ADC, Q3Wk, 4.5 mg/kg.
|
[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 | [1] | ||||
| Efficacy Data | stable disease (SD) |
58%
|
|||
| Patients Enrolled |
Eligible participants require confirmed NHL/RCC with CD70+ status, ≥1 prior systemic therapy failure, measurable lesions (NHL>1.5cm/RCC≥10mm). Key exclusions are prior allogeneic transplant, active secondary malignancy (<3y remission), or previous anti-CD70 therapy.
|
||||
| Administration Dosage |
SGN-75 was administered as an intravenous (IV) infusion without premedication every 3 weeks (Q3Wk), or on Days 1, 8, and 15 of 28-day cycles (weekly). Dose levels assessed were 0.3, 1.0, 1.5, 2.0, 3.0, and 4.5 mg/kg administered Q3Wk and 0.3 and 0.6 mg/kg administered weekly.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT01015911 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1, Open-label, Dose-escalation Study to Evaluate the Safety and Tolerability of SGN-75 in Patients With CD70-positive Relapsed or Refractory Non-Hodgkin Lymphoma or Metastatic Renal Cell Carcinoma | ||||
| Primary Endpoint |
The study evaluates adverse events and lab abnormalities as primary safety outcomes, monitored until 1 month post-treatment.
|
||||
| Other Endpoint |
Secondary objectives include clinical response (assessed every 2 months), duration parameters (every 3 months), pharmacokinetics of SGN-75, and immunogenicity (both tracked through 1 month post-treatment).
|
||||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Eligible patients must have CD70+ metastatic renal cell carcinoma with ≥1 prior TKI, measurable disease, ECOG 0-1, and adequate organ function. Exclusions involve prior anti-CD70 therapy or >1 mTOR inhibitor regimen.
|
||||
| Administration Dosage |
1-2 mg/kg IV every 21 days
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT01677390 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1b, Open-label, Dose-escalation Study to Evaluate the Safety and Tolerability of SGN-75 in Combination With Everolimus in Patients With CD70-positive Metastatic Renal Cell Carcinoma | ||||
| Primary Endpoint |
The primary outcome measures include incidence of adverse events and lab abnormalities assessed up to 1 month post last dose, with clinical response evaluated per RECIST 1.1.
|
||||
| Other Endpoint |
Secondary endpoints cover progression-free survival (expected ~6 months), overall survival (expected ~1 year), SGN-75/metabolite blood levels monitored across cycles, and anti-therapeutic antibody incidence.
|
||||
References