Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0PXQWR
ADC Name
Depatuxizumab mafodotin
Synonyms
ABT-414; ABT-414/806; Depatux-M
   Click to Show/Hide
Organization
AbbVie, Inc.
Drug Status
Phase 3
Indication
In total 3 Indication(s)
Glioblastoma [ICD11:2A00]
Phase 3
Non-small cell lung cancer [ICD11:2C25]
Phase 2
Squamous cell cancer [ICD11:2D60-2D61]
Terminated in phase 1
Drug-to-Antibody Ratio
3.8
Structure
Antibody Name
Depatuxizumab
  Antibody Info 
Antigen Name
Epidermal growth factor receptor (EGFR)
  Antigen Info 
Payload Name
Monomethyl auristatin F
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Maleimido-caproyl
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Mafodotin
Puchem SID
472422986 , 316935918 , 348350491 , 347828090 , 249565653 , 318464514
Drugbank ID
DB11731
ChEBI ID
CHEMBL3707277
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Median progression-free survival (mPFS)  Undisclosed Undisclosed Undisclosed
Median Overall Survival (mOS)  Undisclosed Undisclosed Undisclosed
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 87.5
%
MSTO-211H cells
Pleural biphasic mesothelioma
Half Maximal Inhibitory Concentration (IC50) 
10.00 - 35.00
ug/mL
MSTO-211H cells
Pleural biphasic mesothelioma
Half Maximal Inhibitory Concentration (IC50) 
10.00 - 35.00
ug/mL
NCI-H28 cells
Pleural mesothelioma
Half Maximal Inhibitory Concentration (IC50) 
10.00 - 35.00
ug/mL
NCI-H2052 cells
Pleural mesothelioma
Half Maximal Inhibitory Concentration (IC50) 
10.00 - 35.00
ug/mL
NCI-H2052 cells
Pleural mesothelioma
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Median progression-free survival (mPFS) 8.00 (depatux-m group); 6.30 (placebo group) High EGFR expression (EGFR +++)
Patients Enrolled
EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
Administration Dosage
Depatux-m was dosed at 2.0 mg/kg during RT, then 1.25 mg/kg thereafter on days 1 and 15/28, 19,21 and allowed to continue until disease progression.
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Median Overall Survival (mOS) 18.90 (depatux-m group); 18.70(placebo group) High EGFR expression (EGFR +++)
Patients Enrolled
EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
Administration Dosage
Depatux-m was dosed at 2.0 mg/kg during RT, then 1.25 mg/kg thereafter on days 1 and 15/2819, 21 and allowed to continue until disease progression.
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.50% (Day 40) Positive EGFR expression (EGFR+++/++)
Method Description
To establish xenografts, 2 x 106 MSTO-211H cells mixed with 75-uL Matrigel were injected subcutaneously in the right flank of 5 to 6-week-old female BALB/c nu/nu miceFor the MSTO-211H study, mice received either ABT-414, ABBV-221 or ADC control (3 mg/kg) every 4 days.
In Vivo Model MSTO-211H CDX model
In Vitro Model Pleural biphasic mesothelioma MSTO-211H cells CVCL_1430
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 10.00 ug/mL - 35.00 ug/mL Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural biphasic mesothelioma MSTO-211H cells CVCL_1430
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 10.00 ug/mL - 35.00 ug/mL Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural mesothelioma NCI-H28 cells CVCL_1555
Experiment 4 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 10.00 ug/mL - 35.00 ug/mL Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural mesothelioma NCI-H2052 cells CVCL_1518
Experiment 5 Reporting the Activity Date of This ADC [2]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 10.00 ug/mL - 35.00 ug/mL Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural mesothelioma NCI-H2052 cells CVCL_1518
References
Ref 1 Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial. Neuro Oncol. 2023 Feb 14;25(2):339-350. doi: 10.1093/neuonc/noac173.
Ref 2 Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel). 2020 Oct 2;13(10):289. doi: 10.3390/ph13100289.

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