Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ID: DRG0XRAON)
ADC Name
LOP628
Synonyms
LOP628
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Organization
MorphoSys (Top20 MNC) (Originator);Novartis (Top20 MNC);ImmunoGen (Top20 MNC)
Drug Status
Phase 1 (discontinued)
Drug-to-Antibody Ratio
3.5
Structure
Antibody Name
LMJ729
  Antibody Info 
Antigen Name
Mast/stem cell growth factor receptor Kit (KIT)
  Antigen Info 
Payload Name
DM1
  Payload Info 
Payload Target
Microtubule (MT)
  Target Info 
Linker Name
Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
  Linker Info 
Conjugate Type
Random Lysines
Combination Type
emtansine
2027 Update
The disease landscape of This ADC
2027 Update
The clinical trial pipelines of This ADC
Disease Name Phase 1 Phase 2 Phase 3 Approved
Acute myeloid leukaemia
1 Trials
Clinical trial identifier
NCT02221505
Unspecific solid tumor
1 Trials
Clinical trial identifier
NCT02221505
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  NCT02221505
PHASE1
A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of LOP628, Administered Intravenously in Adult Patients With cKit-positive Tumors and Acute Myeloid Leukemia
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
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
Eligibility criteria require documented cKit-positive neoplasms (solid tumors) or AML with specific progression patterns, measurable disease, and blast count limits (AML). Exclusion criteria address CNS metastases, significant comorbidities, prior cKit-directed antibody therapy, pregnancy, and prior bone marrow transplant (AML), ensuring patient safety while maintaining study validity across both tumor types.

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Administration Dosage
Infusions were given of either 0.3 mg/kg LOP628, without premedication, or 0.15 mg/kg LOP628, with premedication of dexamethasone and cetirizine.
Related Clinical Trial
NCT Number NCT02221505  Clinical Status PHASE1
Clinical Description A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of LOP628, Administered Intravenously in Adult Patients With cKit-positive Tumors and Acute Myeloid Leukemia
Primary Endpoint
The study assesses the incidence of dose-limiting toxicities (DLTs) over 12 months to determine the maximum tolerated dose/recommended dose for expansion (MTD/RDE) of LOP628, evaluating its safety and feasibility at different dosage levels.
Other Endpoint
The trial evaluates multiple safety and efficacy endpoints over 30 months, including adverse event incidence, pharmacokinetics (PK) profiles (AUC, Cmax, etc.), and preliminary anti-tumor activity metrics (ORR, DOR, PFS, DCR, BOR). For AML patients, additional assessments like event-free survival (EFS) and duration of response are included to comprehensively characterize LOP628's therapeutic potential across hematological and solid tumor indications.

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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 [2]
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 [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 46% 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 [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 75% 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 [2]
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 [2]
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 [2]
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 [2]
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 [2]
Efficacy Data Half Maximum Growth Inhibitory Concentration (GI50) < 0.5 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 [2]
Efficacy Data Half Maximum Growth Inhibitory Concentration (GI50) < 1 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 [2]
Efficacy Data Half Maximum Growth Inhibitory Concentration (GI50) > 10 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 Phase 1 Study of LOP628 in Adult Patients With cKit-positive Solid Tumors and Acute Myeloid Leukemia
Ref 2 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.