Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0NEMOV
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| ADC Name |
Losatuxizumab vedotin
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| Synonyms |
losatuxizumab vedotin; ABBV-221
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| Organization |
AbbVie (Top20 MNC) (Originator)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
3
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| Structure |
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| Antibody Name |
Losatuxizumab
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Antibody Info | ||||
| Antigen Name |
Epidermal growth factor receptor (EGFR)
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Antigen Info | ||||
| Payload Name |
MMAE
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
vedotin
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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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| Brain cancer |
1 Trials
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| Breast cancer |
1 Trials
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| Colorectal cancer |
1 Trials
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| Head and neck cancer |
1 Trials
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| Lung cancer |
1 Trials
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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 Patient-derived Xenograft Model
Discovered Using Cell Line-derived Xenograft Model
Revealed Based on the Cell Line 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) |
38%
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| Patients Enrolled |
Eligible participants (ECOG 0-2) must have EGFR-elevated solid tumors (e.g., HNSCC, NSCLC, TNBC) with archived tissue and adequate organ function; expanded safety cohort requires platinum-refractory metastatic lung cancer. Exclusions include recent EGFR antibody use (>Grade 1 unresolved toxicities), IgG-related hypersensitivity, or high-risk conditions per investigator judgment.
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| Administration Dosage |
ABBV-221 will be given either every 3 weeks or 2 weeks on, 1 week off or weekly dosing by intravenous infusion approximately over 30 minutes to 3 hours. This is a dose escalation study, therefore the dose of ABBV-221 will change throughout the study.
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| Related Clinical Trial | |||||
| NCT Number | NCT02365662 | Clinical Status | PHASE1 | ||
| 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 |
This study evaluates the safety profile of ABBV-221 through adverse event monitoring (4 years) and pharmacokinetics (Cmax, AUCt) with blood sampling across multiple cycles (up to ~2 years). The primary objectives include determining the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD), where RPTD selection considers DLT patterns if MTD is reached or PK/safety data if MTD is not achieved.
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| Other Endpoint |
Secondary objectives assess ABBV-221's effect on QT prolongation via ECG monitoring (Cycle 1 Days 1-8, then per cycle) and efficacy via objective response rate (ORR by RECIST 1.1) measured every 2-3 cycles for ~2 years in participants with baseline measurable lesions.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| 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.
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| 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.
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| Other Endpoint |
Stable disease (SD) for at least 2 cycles was observed in 19 patients (42.20%).
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Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 94.90% | 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.
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| In Vivo Model | Malignant Mesothelioma PDX model (PDX: MSTO-211H) | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 98.30% | 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.
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| In Vivo Model | Malignant Mesothelioma PDX model (PDX: MSTO-211H) | ||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 0.23% | 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 | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 5.45% | 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 | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 66.60% | 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 | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | 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
| Experiment 1 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 89.80% | 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.
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| 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.2 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 1 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 4 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 8 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 6 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 8 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 7 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 11 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 69 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 80 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 | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 1000 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 | ||
| Experiment 11 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 1000 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 | ||
References