Linker Information
General Information of This Linker
| Linker ID |
LIN0ATYUQ
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| Linker Name |
Mal-EBE-Mal
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| Linker Type |
Thiol-sensitive linker
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| Antibody-Linker Relation |
Uncleavable
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
BMS-986148 [Phase 2]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
2.00% (All escalation, BMS-986148 monotherapy)
6.00% (All expansion, BMS-986148 monotherapy) 4.00% (Mesothelioma expansion, BMS-986148 monotherapy) 9.00% (Ovarian expansion) 20.00% (All, BMS-986148 + nivolumab) 23.00% (Mesothelioma, BMS-986148 + nivolumab) |
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| Patients Enrolled |
Pleural or peritoneal mesothelioma (except sarcomatoid mesothelioma), ovarian cancer (except mucinous carcinoma), pancreatic cancer, gastric cancer, or non-small cell lung cancer (adenocarcinoma only).
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| Administration Dosage |
BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability.
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| Related Clinical Trial | |||||
| NCT Number | NCT02341625 | Clinical Status | Phase 1/2a | ||
| Clinical Description |
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
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| Primary Endpoint |
The MTD and the recommended dose for the part 2 monotherapy expansion is BMS-986148 1.20 mg/kg every 3 weeks dose level. The MTD in the combination expansion cohort is BMS-986148 0.80 mg/kg + nivolumab 360 mg every 3 weeks.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT02341625 | Clinical Status | Phase 1/2 | ||
| Clinical Description |
A phase 1/2a study of BMS-986148, a mesothelin directed antibody drug conjugate, in subjects with select advanced solid tumors.
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| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT02884726 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1 study of the safety and tolerability of BMS 986148 in subjects with advanced and/or metastatic solid tumors.
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MUC16-55 ADC [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100.00% (Day 50) | Positive MUC16 expression (MUC16 +++/++) | ||
| Method Description |
In vivo efficacy of MUC16 targeting ADCs in the Ovcar3 tumor model. MUC16-55 ADC dosed at 5 mg/kg (in each study with the exact dosing for control) IV in SCID mice.
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| In Vivo Model | OVCR-3 CDX model | ||||
| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.80 nM
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Positive MUC16 expression (MUC16 +++/++) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Negative MUC16 expression (MUC16-) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Normal | HEK293 cells | CVCL_0045 | ||
MUC16-56 ADC [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.83 nM
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Positive MUC16 expression (MUC16 +++/++) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Negative MUC16 expression (MUC16-) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Normal | HEK293 cells | CVCL_0045 | ||
3A5-56 ADC [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.18 nM
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Positive MUC16 expression (MUC16 +++/++) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Negative MUC16 expression (MUC16-) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Normal | HEK293 cells | CVCL_0045 | ||
3A5-55 ADC [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.40 nM
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Positive MUC16 expression (MUC16 +++/++) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Ovarian serous adenocarcinoma | OVCAR-3 cells | CVCL_0465 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Negative MUC16 expression (MUC16-) | ||
| Method Description |
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
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| In Vitro Model | Normal | HEK293 cells | CVCL_0045 | ||
Glypican 3 ADC [Terminated in phase 1]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
100.00%
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Positive GPC3 expression (GPC3+++/++) | ||
| Method Description |
Female NOD/SCID mice were inoculated subcutaneously in the right flank with 500,000 Hep3B cells. Three weekly administration of A2-tub at 0.12 mol/kg.
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| In Vivo Model | Hep3B CDX model | ||||
| In Vitro Model | Childhood hepatocellular carcinoma | Hep 3B2.1-7 cells | CVCL_0326 | ||
References
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