Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0XRAON
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| ADC Name |
LOP628
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| Synonyms |
LOP628
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| Organization |
MorphoSys (Top20 MNC) (Originator);Novartis (Top20 MNC);ImmunoGen (Top20 MNC)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
3.5
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| Structure |
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| Antibody Name |
LMJ729
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Antibody Info | ||||
| Antigen Name |
Mast/stem cell growth factor receptor Kit (KIT)
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Antigen Info | ||||
| Payload Name |
DM1
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
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Linker Info | ||||
| Conjugate Type |
Random Lysines
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| Combination Type |
emtansine
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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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| Acute myeloid leukaemia |
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
Discovered Using Cell Line-derived Xenograft Model
Revealed Based on the Cell Line Data
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
| 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.
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| 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% | 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.
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| 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% | 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| 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.
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| 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 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.
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| 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 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.
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| In Vitro Model | Breast adenocarcinoma | MDA-MB-468 cells | CVCL_0419 | ||
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| 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.
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| 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.
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| 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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References