Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0NEMOV
ADC Name
Losatuxizumab vedotin
Synonyms
ABBV-221; ABBV221; ABBV 224
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Organization
AbbVie, Inc.
Drug Status
Phase 1
Indication
In total 1 Indication(s)
Solid tumors [ICD11:2A00-2A0Z|2B50-2F9Z]
Phase 1
Drug-to-Antibody Ratio
3
Antibody Name
Losatuxizumab
  Antibody Info 
Antigen Name
Epidermal growth factor receptor (EGFR)
  Antigen Info 
Payload Name
Monomethyl auristatin E
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Mc-Val-Cit-PABC
  Linker Info 
Conjugate Type
Random conjugation through reduced inter-chain cysteines.
Combination Type
Vedotin
Puchem SID
472405979 , 381127931 , 440234870
ChEBI ID
CHEMBL4594515
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT02365662
Phase 1
A phase 1 study of ABBV-221 in subjects with advanced solid tumor types likely to exhibit elevated levels of epidermal growth factor receptor.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
94.9
%
Malignant Mesothelioma PDX model (PDX: MSTO-211H)
Tumor Growth Inhibition value (TGI) 
98.3
%
Malignant Mesothelioma PDX model (PDX: MSTO-211H)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 0.23
%
NCI-H292 cells
Lung mucoepidermoid carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 5.45
%
NCI-H441 cells
Lung papillary adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 66.6
%
EBC-1 cells
Lung squamous cell carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 100
%
NCI-H1703 cells
Lung squamous cell carcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 11 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 89.8
%
MSTO-211H cells
Pleural biphasic mesothelioma
Half Maximal Inhibitory Concentration (IC50) 
0.2
nM
U87MGde2-7 cells (EGFRvIII overexpression)
Glioblastoma
Half Maximal Inhibitory Concentration (IC50) 
1
nM
A431 cells
Skin squamous cell carcinoma
Half Maximal Inhibitory Concentration (IC50) 
4
nM
NCI-H1703 cells
Lung squamous cell carcinoma
Half Maximal Inhibitory Concentration (IC50) 
8
nM
NCI-H292 cells
Lung mucoepidermoid carcinoma
Half Maximal Inhibitory Concentration (IC50) 
8
nM
LoVo cells
Colon adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
11
nM
HCC827ER cells
Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
69
nM
EBC-1 cells
Lung squamous cell carcinoma
Half Maximal Inhibitory Concentration (IC50) 
80
nM
NCI-H441 cells
Lung papillary adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
> 1000
nM
HCT 15 cells
Colon adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
> 1000
nM
SW620 cells
Colon adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Patients Enrolled
Patients with advanced solid tumor types typically associated with elevated levels of EGFR expression (e.g., head and neck squamous cell carcinoma [HNC], non-small cell lung cancer [NSCLC], triple-negative breast cancer, colorectal carcinoma, and GBM.
Administration Dosage
A standard 3+3 design; intravenous (IV) infusion to groups of 3 to 6 patients. An every-3-week dosing cycle (0.30, 0.45, 0.67, 1.00, 1.50, 2.00, or 2.25 mg/kg losatuxizumab vedotin every 3 weeks [Q3W]) or alternative dosing schedules were evaluated (2.00 or 3.00 mg/kg losatuxizumab vedotin for 2 weeks on, 1 week off, or 4.50 or 6.00 mg/kg losatuxizumab vedotin weekly [over 3 weeks total]).

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Related Clinical Trial
NCT Number NCT02365662  Clinical Status Phase 1
Clinical Description A phase 1 study of ABBV-221 in subjects with advanced solid tumor types likely to exhibit elevated levels of epidermal growth factor receptor.
Primary Endpoint
The maximum tolerated dose (MTD) was not achieved.
Other Endpoint
Stable disease (SD) for at least 2 cycles was observed in 19 patients (42.20%).
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) 94.90% (Day 49) High HER2 expression (HER2+++)
Method Description
In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor model.ABT-414 treatment 3 mg/kg q4 days.
In Vivo Model Malignant Mesothelioma PDX model (PDX: MSTO-211H)
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) 98.30% (Day 49) High HER2 expression (HER2+++)
Method Description
In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor model.ABBV-221 treatment 3 mg/kg q4 days.
In Vivo Model Malignant Mesothelioma PDX model (PDX: MSTO-211H)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.23% (Day 120) Low EGFR expression (EGFR+)
Method Description
To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm3. Treatments ABBV-221 at 6 mg/kg every 4th day by intraperitoneal injection.

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In Vivo Model NCI-H292 lung xenograft tumor model
In Vitro Model Lung mucoepidermoid carcinoma NCI-H292 cells CVCL_0455
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 5.45% (Day 95) Low EGFR expression (EGFR+)
Method Description
To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm3. Treatments ABBV-221 at 3 mg/kg every 4th day by intraperitoneal injection.

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In Vivo Model NCI-H441 lung xenograft tumor model
In Vitro Model Lung papillary adenocarcinoma NCI-H441 cells CVCL_1561
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.60% (Day 113) High EGFR expression (EGFR+++)
Method Description
To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm3. Treatments ABBV-221 at 4 mg/kg every 4th day by intraperitoneal injection.

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In Vivo Model EBC1 lung xenograft tumor model
In Vitro Model Lung squamous cell carcinoma EBC-1 cells CVCL_2891
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 113) High EGFR expression (EGFR+++)
Method Description
To generate xenografts, a suspension of viable tumors cells mixed with an equal amount of Matrigel was injected subcutaneously into the flank of 6- to 8-week old mice. The injection volume was 0.2 mL composed of a 1:1 mixture of S-MEM and Matrigel. Tumors were size matched at approximately 200-250 mm3. Treatments ABBV-221 at 1 mg/kg every 4th day by intraperitoneal injection.

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In Vivo Model NCI-H1703 lung xenograft tumor model
In Vitro Model Lung squamous cell carcinoma NCI-H1703 cells CVCL_1490
Revealed Based on the Cell Line Data
Click To Hide/Show 11 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 89.80% (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 [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 0.20 nM Positive EGFR vIII expression (EGFR vIII+++/++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Glioblastoma U87MGde2-7 cells (EGFRvIII overexpression) CVCL_0022
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 1.00 nM High EGFR expression (EGFR+++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Skin squamous cell carcinoma A431 cells CVCL_0037
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 4.00 nM High EGFR expression (EGFR+++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Lung squamous cell carcinoma NCI-H1703 cells CVCL_1490
Experiment 5 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 8.00 nM High EGFR expression (EGFR+++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Lung mucoepidermoid carcinoma NCI-H292 cells CVCL_0455
Experiment 6 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 8.00 nM High EGFR expression (EGFR+++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Colon adenocarcinoma LoVo cells CVCL_0399
Experiment 7 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 11.00 nM High EGFR expression (EGFR+++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Lung adenocarcinoma HCC827ER cells CVCL_V408
Experiment 8 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 69.00 nM Moderate EGFR expression (EGFR++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Lung squamous cell carcinoma EBC-1 cells CVCL_2891
Experiment 9 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 80.00 nM Moderate EGFR expression (EGFR++)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Lung papillary adenocarcinoma NCI-H441 cells CVCL_1561
Experiment 10 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1000.00 nM Low EGFR expression (EGFR+)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Colon adenocarcinoma HCT 15 cells CVCL_0292
Experiment 11 Reporting the Activity Date of This ADC [3]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 1000.00 nM Low EGFR expression (EGFR+)
Method Description
Cells were plated at 1,000 to 3,000 cells/well in complete growth medium containing 10% FBS in 96-well plates. The following day medium was removed and replaced with fresh media containing titrations of antibodies or ADCs, and cells were incubated for 72 hours at 37°C in a humidified CO2 incubator. Cell viability was then assessed using an ATPlite luminescence assay.Cell viability was determined following incubation with ABBV-221 for 72 hours.

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In Vitro Model Colon adenocarcinoma SW620 cells CVCL_0547
References
Ref 1 A phase 1 study evaluating safety and pharmacokinetics of losatuxizumab vedotin (ABBV-221), an anti-EGFR antibody-drug conjugate carrying monomethyl auristatin E, in patients with solid tumors likely to overexpress EGFR. Invest New Drugs. 2020 Oct;38(5):1483-1494.
Ref 2 Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel). 2020 Oct 2;13(10):289.
Ref 3 Characterization of ABBV-221, a Tumor-Selective EGFR-Targeting Antibody Drug Conjugate. Mol Cancer Ther. 2018 Apr;17(4):795-805.
Ref 4 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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