Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0XRAON
ADC Name
LOP-628
Synonyms
Anti-c-kit humanised IgG1kappa antibody-maitansine conjugate; Anti-c-kit humanised IgG1 kappa antibody-maytansine conjugate; Anti-proto-oncogene protein; Anti-proto-oncogene protein c-kit IgG1 kappa antibody-maitansine conjugate; LOP 628; Anti-c-kit humanised IgG1 kappa antibody-maitansine conjugate (Novartis Pharma AG); LOP628
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Organization
Novartis Pharma AG; Novartis AG
Drug Status
Terminated in phase 1
Indication
In total 2 Indication(s)
Acute myelogenous leukemia [ICD11:2B33]
Terminated in phase 1
Solid tumors [ICD11:2A00-2A0Z|2B50-2F9Z]
Terminated in phase 1
Drug-to-Antibody Ratio
3.5
Structure
Antibody Name
humanized Anti-KIT mAb LMJ729
  Antibody Info 
Antigen Name
Mast/stem cell growth factor receptor Kit (KIT)
  Antigen Info 
Payload Name
Mertansine DM1
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
  Linker Info 
Conjugate Type
Random conjugation through nucleophilic lysines.
Combination Type
Emtansine
General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 43.3
%
GIST430 cells
Gastrointestinal stromal tumor
Tumor Growth Inhibition value (TGI) 
≈ 46
%
NCI-H1048 cells
Lung small cell carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 75
%
GIST430 cells
Gastrointestinal stromal tumor
Tumor Growth Inhibition value (TGI) 
≈ 80.2
%
GIST-T1 cells
Gastrointestinal stromal tumor
Tumor Growth Inhibition value (TGI) 
82.2
%
GIST-T1 cells
Gastrointestinal stromal tumor
Tumor Growth Inhibition value (TGI) 
≈ 87.3
%
NCI-H1048 cells
Lung small cell carcinoma
Tumor Growth Inhibition value (TGI) 
≈ 93.3
%
NCI-H1048 cells
Lung small cell carcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximum Growth Inhibitory Concentration (GI50) 
< 0.5
nM
GIST-T1 cells
Gastrointestinal stromal tumor
Half Maximum Growth Inhibitory Concentration (GI50) 
< 1
nM
NCI-H526 cells
Lung small cell carcinoma
Half Maximum Growth Inhibitory Concentration (GI50) 
> 10
nM
MDA-MB-468 cells
Breast adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.30% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive GIST430 xenograft model. Animals were administered a single i.v. injection of the vehicle, IgG-ADC, or LOP628, LMJ729, imatinib.
In Vivo Model KIT-expressing GIST430 xenograft model
In Vitro Model Gastrointestinal stromal tumor GIST430 cells CVCL_7040
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 46.00% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive NCI-H1048 SCLC xenograft model. Animals were administered a single i.v. injection of the vehicle, IgG-ADC, or LOP628; twice daily 80 mg/kg oral doses of imatinib or the combination of LOP628 with imatinib.
In Vivo Model KIT-expressing NCI-H1048 SCLC xenograft model
In Vitro Model Lung small cell carcinoma NCI-H1048 cells CVCL_1453
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 75.00% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive GIST430 xenograft model. Animals were administered a single i.v. injection of the vehicle, IgG-ADC, or LOP628, LMJ729, imatinib.
In Vivo Model KIT-expressing GIST430 xenograft model
In Vitro Model Gastrointestinal stromal tumor GIST430 cells CVCL_7040
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 80.20% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive GIST-T1 xenograft model. Animals were administered a single i.v. injection of the vehicle, IgG-ADC, or LOP628; twice daily 80 mg/kg oral doses of imatinib or the combination of LOP628 with imatinib.
In Vivo Model KIT-expressing GIST-T1 xenograft model
In Vitro Model Gastrointestinal stromal tumor GIST-T1 cells CVCL_4976
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) 82.20% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive GIST-T1 xenograft model. An efficacy study (single 0.625 mg/kg dose) in the GIST-T1 xenograft model in mice was performed.
In Vivo Model KIT-expressing GIST-T1 xenograft model
In Vitro Model Gastrointestinal stromal tumor GIST-T1 cells CVCL_4976
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.30% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive NCI-H1048 SCLC xenograft model. Animals were administered a single i.v. injection of the vehicle, IgG-ADC, or LOP628; twice daily 80 mg/kg oral doses of imatinib or the combination of LOP628 with imatinib.
In Vivo Model KIT-expressing NCI-H1048 SCLC xenograft model
In Vitro Model Lung small cell carcinoma NCI-H1048 cells CVCL_1453
Experiment 7 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.30% Positive KIT expression (KIT+++/++)
Method Description
The in vivo antitumor activity of LOP-628 was evaluated in a c-KIT positive NCI-H1048 SCLC xenograft model. Animals were administered a single i.v. injection of the vehicle, IgG-ADC, or LOP628; twice daily 80 mg/kg oral doses of imatinib or the combination of LOP628 with imatinib.
In Vivo Model KIT-expressing NCI-H1048 SCLC xenograft model
In Vitro Model Lung small cell carcinoma NCI-H1048 cells CVCL_1453
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximum Growth Inhibitory Concentration (GI50) < 0.50 nM Positive KIT expression (KIT+++/++)
Method Description
The inhibitory activity of LOP-628 against cancer cell growth was compared with LMJ729 against cancer cell growth in vitro.
In Vitro Model Gastrointestinal stromal tumor GIST-T1 cells CVCL_4976
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximum Growth Inhibitory Concentration (GI50) < 1.00 nM Positive KIT expression (KIT+++/++)
Method Description
The inhibitory activity of LOP-628 against cancer cell growth was compared with LMJ729 against cancer cell growth in vitro.
In Vitro Model Lung small cell carcinoma NCI-H526 cells CVCL_1569
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Half Maximum Growth Inhibitory Concentration (GI50) > 10.00 nM Negative KIT expression (KIT-)
Method Description
The inhibitory activity of LOP-628 against cancer cell growth was compared with LMJ729 against cancer cell growth in vitro.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
References
Ref 1 Preclinical Antitumor Activity of a Novel Anti-c-KIT Antibody-Drug Conjugate against Mutant and Wild-type c-KIT-Positive Solid Tumors. Clin Cancer Res. 2018 Sep 1;24(17):4297-4308.

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