Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0ATULB
ADC Name
Laprituximab emtansine
Synonyms
laprituximab emtansine; IMGN289
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Organization
ImmunoGen (Top20 MNC) (Originator)
Drug Status
Phase 1 (discontinued)
Drug-to-Antibody Ratio
3 to 4
Structure
Antibody Name
Laprituximab
  Antibody Info 
Antigen Name
Epidermal growth factor receptor (EGFR)
  Antigen Info 
Payload Name
DM1
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
  Linker Info 
Conjugate Type
Random Lysines
Combination Type
emtansine
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
Unspecific solid tumor
1 Trials
Trial ID
NCT01963715
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
Undisclosed  NCT01963715
PHASE1
A Phase 1, Multi-center, Open-label Study of IMGN289 Administered Intravenously in Adult Patients With EGFR-positive Solid Tumors
Undisclosed  NCT01963715
Phase 1
A phase 1, multi-center, open-label study of IMGN289 administered intravenously in adult patients with EGFR-positive solid tumors.
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) 
58.3
%
FaDu cells
Hypopharyngeal squamous cell carcinoma
Tumor Growth Inhibition value (TGI) 
83.3
%
HSC-2 cells
Oral cavity squamous cell carcinoma
Minimal Effective Dose (MED) 
1
mg/kg
FaDu cells
Hypopharyngeal squamous cell carcinoma
Minimal Effective Dose (MED) 
2.5
mg/kg
HSC-2 cells
Oral cavity squamous cell carcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
0.25
nM
HNSCC cells
Head and neck squamous cell carcinoma
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]
Patients Enrolled
Eligibility requires EGFR-positive solid tumor patients (≥18 years) with progressed/refractory disease, adequate organ function, and contraception adherence. Exclusions involve concurrent anticancer therapy, symptomatic brain metastases, uncontrolled comorbidities, high-risk skin conditions, or prior severe EGFR-therapy rash. Active HIV/hepatitis or pregnancy also disqualifies participants.

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Administration Dosage
.
Related Clinical Trial
NCT Number NCT01963715  Clinical Status PHASE1
Clinical Description A Phase 1, Multi-center, Open-label Study of IMGN289 Administered Intravenously in Adult Patients With EGFR-positive Solid Tumors
Primary Endpoint
The study evaluates dose-limiting toxicities in participants over 2 years, focusing on safety and tolerability metrics as primary endpoints.
Other Endpoint
Secondary endpoints include monitoring adverse events, pharmacokinetic parameters (plasma concentration AUC, Cmax of IMGN289), immunogenicity (HAHA/HADA), and preliminary anti-tumor activity via RECIST 1.1 criteria over 2 years.
Experiment 2 Reporting the Activity Date of This ADC [2]
Related Clinical Trial
NCT Number NCT01963715  Clinical Status Phase 1
Clinical Description A phase 1, multi-center, open-label study of IMGN289 administered intravenously in adult patients with EGFR-positive solid tumors.
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) 58.30% High EGFR expression (EGFR+++/++)
Method Description
The cytotoxic activity of IMGN289 was evaluated against a panel of SCCHN cell lines in vitro. Immunodeficient mice bearing established subcutaneous xenograft tumors were treated with a single intravenous injection of IMGN289 at 1,2.5 or 5.0 mg/kg (based on antibody concentration). IMGN289 dose was 5 mg/kg administered as a single injection.
In Vivo Model Head and neck squamous cell carcinomas CDX model
In Vitro Model Hypopharyngeal squamous cell carcinoma FaDu cells CVCL_1218
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) 83.30% High EGFR expression (EGFR+++/++)
Method Description
The cytotoxic activity of IMGN289 was evaluated against a panel of SCCHN cell lines in vitro. Immunodeficient mice bearing established subcutaneous xenograft tumors were treated with a single intravenous injection of IMGN289 at 1,2.5 or 5.0 mg/kg (based on antibody concentration). IMGN289 dose was 5 mg/kg administered as a single injection.
In Vivo Model Head and neck squamous cell carcinomas CDX model
In Vitro Model Oral cavity squamous cell carcinoma HSC-2 cells CVCL_1287
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Minimal Effective Dose (MED) 1 mg/kg High EGFR expression (EGFR+++/++)
Method Description
The cytotoxic activity of IMGN289 was evaluated against a panel of SCCHN cell lines in vitro. Immunodeficient mice bearing established subcutaneous xenograft tumors were treated with a single intravenous injection of IMGN289 at 1,2.5 or 5.0 mg/kg (based on antibody concentration).
In Vivo Model Head and neck squamous cell carcinomas CDX model
In Vitro Model Hypopharyngeal squamous cell carcinoma FaDu cells CVCL_1218
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Minimal Effective Dose (MED) 2.5 mg/kg High EGFR expression (EGFR+++/++)
Method Description
The cytotoxic activity of IMGN289 was evaluated against a panel of SCCHN cell lines in vitro. Immunodeficient mice bearing established subcutaneous xenograft tumors were treated with a single intravenous injection of IMGN289 at 1,2.5 or 5.0 mg/kg (based on antibody concentration).
In Vivo Model Head and neck squamous cell carcinomas CDX model
In Vitro Model Oral cavity squamous cell carcinoma HSC-2 cells CVCL_1287
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 0.25 nM High EGFR expression (EGFR+++/++)
Method Description
Effects of IMGN289 on clonogenicity and proliferation were tested in HNSCC cell lines with varying cetuximab and gefitinib sensitivities.
In Vitro Model Head and neck squamous cell carcinoma HNSCC cells Homo sapiens
References
Ref 1 A Phase 1 Study of IMGN289 in Adult Patients With EGFR-positive Solid Tumors
Ref 2 A Phase 1, Multi-center, Open-label Study of IMGN289 Administered Intravenously in Adult Patients With EGFR-positive Solid Tumors
Ref 3 Preclinical evaluation of IMGN289, an anti-EGFR antibody-maytansinoid conjugate for the treatment of squamous cell carcinoma of the head and neck.
Ref 4 Antitumor effect of IMGN289, an anti-EGFR antibody-drug conjugate (ADC), in preclinical models of head and neck squamous cell carcinomas (HNSCC). Journal of Clinical Oncology 32, no. 15_suppl.