Linker Information
General Information of This Linker
| Linker ID |
LIN0FFWID
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| Linker Name |
PEGylated β-glucuronide linker
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| Antibody-Linker Relation |
Cleavable
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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
SGN-CD48A [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03379584 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1 study of SGN-CD48A in patients with relapsed or refractory multiple myeloma.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Eligible patients must have MM requiring systemic treatment (per IMWG) refractory to prior PI, IMiD, and anti-CD38 antibody therapy, with measurable disease and adequate organ function (ECOG 0-1). Key exclusions: Grade 2+ neuropathy, recent malignancies (past 3 years), active CNS disease, uncontrolled infections (HIV/HBV/HCV), prior allogeneic transplant, recent cardiovascular events, or use of P-gp/CYP3A modulators within 14 days.
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| Administration Dosage |
Intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle
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| Related Clinical Trial | |||||
| NCT Number | NCT03379584 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase 1 Study of SGN-CD48A in Patients With Relapsed or Refractory Multiple Myeloma
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| Primary Endpoint |
Safety outcomes monitor adverse events (AEs) including severity, seriousness, and relatedness through 1 month after the last dose, along with laboratory abnormalities and dose-limiting toxicities (DLTs) within 3 weeks of first treatment.
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| Other Endpoint |
Efficacy measures include objective response rate (ORR; stringent CR/CR/VGPR/PR), CR rate, duration of response (DOR and CR duration up to ~3 years), PFS, OS, pharmacokinetics (blood concentrations of SGN-CD48A/metabolites), and incidence of antitherapeutic antibodies.
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Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
75%
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Positive SLAMF2 expression (SLAMF2+++/++) | ||
| Method Description |
SGN-CD48A was evaluated in vivo for antitumor activity in a diffuse MM cell line xenograft model in mice. SGN-CD48A was administered at a single dose of 0.30 mg/kg.
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| In Vivo Model | Multiple myeloma CDX model | ||||
| In Vitro Model | Plasma cell myeloma | EJM cells | CVCL_2030 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
87.50%
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Positive SLAMF2 expression (SLAMF2+++/++) | ||
| Method Description |
SGN-CD48A was evaluated in vivo for antitumor activity in a diffuse MM cell line xenograft model in mice. SGN-CD48A was administered at a single dose of 1.00 mg/kg.
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| In Vivo Model | Multiple myeloma CDX model | ||||
| In Vitro Model | Plasma cell myeloma | U-266 cells | CVCL_0015 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
100%
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Positive SLAMF2 expression (SLAMF2+++/++) | ||
| Method Description |
SGN-CD48A was evaluated in vivo for antitumor activity in a diffuse MM cell line xenograft model in mice. SGN-CD48A was administered at a single dose of 0.30 mg/kg.
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| In Vivo Model | Multiple myeloma CDX model | ||||
| In Vitro Model | Plasma cell myeloma | NCI-H929 cells | CVCL_1600 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) |
1.00-11.00 ng/mL
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High CD48 expresion (CD48+++/++; 1260 MSLN molecules/cell) | ||
| Method Description |
Cytotoxic activity of SGN-CD48A was demonstrated in a panel of human MM cell lines in vitro.
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| In Vitro Model | Multiple myeloma | Multiple myeloma cells | Homo sapiens | ||
References